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/TT1 1 Tf
1.215 0 Td
(Exclusion criteria included a history or presence of clinically signific\
ant )Tj
0 -1.143 Td
(medical conditions, including respiratory tract infection, asthma, sever\
e )Tj
0 -1.143 Td
(allergic reactions, and foot allergies)Tj
1 0.8 0.38 0.29 k
/GS0 gs
/TT0 1 Tf
8 0 0 8 300.4724 512.0453 Tm
(Study design)Tj
0.6 0 0.06 0 k
/TT1 1 Tf
/Span<>> BDC
7 0 0 7 304.034 502.628 Tm
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(This was an open-label, 2-part comparative bioavailability study to comp\
are )Tj
0 -1.143 Td
(PK and pharmacodynamics after epinephrine IN or IM)Tj
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
-0.706 -1.345 Td
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(Part 1 was conducted as a randomized, 3-treatment, 5-period, semi-replic\
ate )Tj
0 -1.143 Td
(design \()Tj
/TT0 1 Tf
3.558 0 Td
(Figure 1A)Tj
/TT1 1 Tf
(\))Tj
0.6 0 0.06 0 k
/GS0 gs
-3.558 -1.345 Td
(\225)Tj
/Span<>> BDC
( )Tj
EMC
0 0 0 1 k
/GS1 gs
1.215 0 Td
(Participants received a single administration of each per period:)Tj
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
0.657 -1.345 Td
( )Tj
EMC
-0.556 0 Td
(\226)Tj
0 0 0 1 k
/GS1 gs
1.215 0 Td
(A: Epinephrine 6.6 mg IN via nasal spray)Tj
0.6 0 0.06 0 k
/GS0 gs
0 -1.345 Td
(\225)Tj
/Span<>> BDC
( )Tj
EMC
0 0 0 1 k
/GS1 gs
1.215 0 Td
(Participants were instructed to breathe normally through their mouth )Tj
0 -1.143 Td
(during IN administration)Tj
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
-1.902 -1.345 Td
( )Tj
EMC
-0.528 0 Td
(\226)Tj
0 0 0 1 k
/GS1 gs
-0.028 Tc 1.215 0 Td
(B: Epinephrine 0.3 mg IM via EpiPen)Tj
0 Tc 4.081 0 0 4.081 434.2289 433.8724 Tm
(\256)Tj
-0.028 Tc 7 0 0 7 437.1216 431.5414 Tm
[( \(Mylan Specialty LP)128.9 (, Canonsburg, P)73.7 (A\))]TJ
0.6 0 0.06 0 k
/GS0 gs
0 Tc /Span<>> BDC
-16.434 -1.345 Td
( )Tj
EMC
-0.556 0 Td
(\226)Tj
0 0 0 1 k
/GS1 gs
1.215 0 Td
[(C: )120.2 (Epinephrine 0.5 m)-1.3 (g IM via manual syringe )]TJ
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
-3.237 -1.345 Td
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(Part 2 was a randomized, 3-treatment, 3-period crossover design conducte\
d )Tj
0 -1.143 Td
(in parallel with part 1 \()Tj
/TT0 1 Tf
9.782 0 Td
(Figure 1A)Tj
/TT1 1 Tf
(\))Tj
0.6 0 0.06 0 k
/GS0 gs
-9.782 -1.345 Td
(\225)Tj
/Span<>> BDC
( )Tj
EMC
0 0 0 1 k
/GS1 gs
1.215 0 Td
(Participants received treatments twice \(\2232 x\224\) 5 minutes apart p\
er period:)Tj
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
0.657 -1.345 Td
( )Tj
EMC
-0.556 0 Td
(\226)Tj
0 0 0 1 k
/GS1 gs
1.215 0 Td
(D: Epinephrine 2 x 6.6 mg IN in opposite nostrils)Tj
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
-0.659 -1.345 Td
( )Tj
EMC
-0.556 0 Td
(\226)Tj
0 0 0 1 k
/GS1 gs
1.215 0 Td
(E: Epinephrine 2 x 6.6 mg IN in the same nostril)Tj
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
-0.659 -1.345 Td
( )Tj
EMC
-0.556 0 Td
(\226)Tj
0 0 0 1 k
/GS1 gs
1.215 0 Td
(F: Epinephrine 2 x 0.3 mg IM in opposite thighs)Tj
1 0.8 0.38 0.29 k
/GS0 gs
/TT0 1 Tf
8 0 0 8 300.4724 353.7855 Tm
(PK)Tj
0.6 0 0.06 0 k
/TT1 1 Tf
/Span<>> BDC
7 0 0 7 304.0339 344.3682 Tm
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(Blood samples were collected at specified times to measure plasma )Tj
0 -1.143 Td
(epinephrine \()Tj
/TT0 1 Tf
5.837 0 Td
(Figure 1B)Tj
/TT1 1 Tf
(\))Tj
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
-6.543 -1.345 Td
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(PK parameters included maximum observed concentration \(C)Tj
4.081 0 0 4.081 500.0066 325.5508 Tm
(max)Tj
7 0 0 7 507.7162 326.9508 Tm
(\), time to )Tj
-28.391 -1.143 Td
(reach C)Tj
4.081 0 0 4.081 333.4866 317.5508 Tm
(max)Tj
7 0 0 7 341.1962 318.9508 Tm
( \(T)Tj
4.081 0 0 4.081 349.748 317.5508 Tm
(max)Tj
7 0 0 7 357.4576 318.9508 Tm
(\), area under the plasma concentration-time curve \(AUC\) from )Tj
-6.926 -1.143 Td
(time 0 to the 20-minute postdose time point \(AUC)Tj
4.081 0 0 4.081 462.2722 309.5508 Tm
(0\22620)Tj
7 0 0 7 471.3509 310.9508 Tm
[(\), and )54.7 (AUC from time 0 to )]TJ
-23.196 -1.143 Td
(the 360-minute postdose time point \(AUC)Tj
4.081 0 0 4.081 437.3758 301.5508 Tm
(0\226360)Tj
7 0 0 7 448.724 302.9508 Tm
(\))Tj
ET
0.293 w
/GS2 gs
q 1 0 0 1 1621.8375 467.4965 cm
0 0 m
0 285.954 l
S
Q
0.241 w
q 1 0 0 1 1371.2882 753.5709 cm
0 0 m
250.696 0 l
S
Q
q 1 0 0 1 1371.2882 467.3757 cm
0 0 m
250.696 0 l
S
Q
0.346 w
q 1 0 0 1 1371.4609 467.4965 cm
0 0 m
0 285.954 l
S
Q
BT
1 0.8 0.38 0.29 k
/GS0 gs
/TT0 1 Tf
6 0 0 6 1371.4609 764.8229 Tm
[(Figure 3. Unadjusted and Baseline-Corrected Mean Heart Rate\226T)17.3 (ime Profiles )36.8 (After )]TJ
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(Epinephrine IN or IM in Part 1 \(A\) and Part 2 \(B\))Tj
ET
/PlacedGraphic /MC0 BDC
EMC
BT
0 0 0 1 k
/T1_0 1 Tf
0 6 -6 0 1382.8278 654.817 Tm
(Heart Rate \(bpm)Tj
7.392 0 Td
(\))Tj
ET
0 0 0 1 K
0.5 w 2 J
q 1 0 0 1 1406.4523 647.865 cm
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2.835 0 l
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2.835 -11.066 l
0 -22.131 m
2.835 -22.131 l
0 83.667 m
2.835 83.667 l
0 72.533 m
2.835 72.533 l
0 61.399 m
2.835 61.399 l
0 50.266 m
2.835 50.266 l
0 39.132 m
2.835 39.132 l
0 27.998 m
2.835 27.998 l
0 16.865 m
2.835 16.865 l
4.11 -26.241 m
4.11 -23.406 l
19.644 -26.241 m
19.644 -23.406 l
35.177 -26.241 m
35.177 -23.406 l
50.71 -26.241 m
50.71 -23.406 l
66.244 -26.241 m
66.244 -23.406 l
81.778 -26.241 m
81.778 -23.406 l
97.311 -26.241 m
97.311 -23.406 l
112.844 -26.241 m
112.844 -23.406 l
128.377 -26.241 m
128.377 -23.406 l
143.912 -26.241 m
143.912 -23.406 l
159.445 -26.241 m
159.445 -23.406 l
174.978 -26.241 m
174.978 -23.406 l
190.511 -26.241 m
190.511 -23.406 l
206.044 -26.241 m
206.044 -23.406 l
S
Q
BT
6 0 0 6 1405.4738 616.0399 Tm
(\0373)Tj
1.463 Tc -1.463 Tw (00)Tj
0 Tc 0 Tw 5.47 0 Td
(30)Tj
2.589 0 Td
(60)Tj
2.589 0 Td
(90)Tj
2.311 0 Td
(120)Tj
2.589 0 Td
(150)Tj
/T1_1 1 Tf
7 0 0 7 1379.3302 743.825 Tm
(A. Part )Tj
(1)Tj
/T1_0 1 Tf
4.5 0 0 4.5 1427.3906 744.2502 Tm
(A: Epinephrine 6.6 mg IN, unadjuste)Tj
16.066 0 Td
(d)Tj
-16.066 -1.111 Td
(A: Epinephrine 6.6 mg IN, baseline-correcte)Tj
19.4 0 Td
(d)Tj
-19.4 -1.111 Td
(B1: Epinephrine 0.3 mg IM, autoinjecto)Tj
-0.055 Tc 0.055 Tw 17.233 0 Td
(r,)Tj
0 Tc 0 Tw 0.556 0 Td
( first administration, unadjuste)Tj
13.285 0 Td
(d)Tj
-31.073 -1.111 Td
(B1: Epinephrine 0.3 mg IM, autoinjecto)Tj
-0.055 Tc 0.055 Tw 17.233 0 Td
(r,)Tj
0 Tc 0 Tw 0.556 0 Td
( first administration, baseline-correcte)Tj
16.618 0 Td
(d)Tj
-34.407 -1.111 Td
(B2: Epinephrine 0.3 mg IM, autoinjecto)Tj
-0.055 Tc 0.055 Tw 17.233 0 Td
(r,)Tj
0 Tc 0 Tw 0.556 0 Td
( second administration, unadjuste)Tj
14.899 0 Td
(d)Tj
-32.688 -1.111 Td
(B2: Epinephrine 0.3 mg IM, autoinjecto)Tj
-0.055 Tc 0.055 Tw 17.233 0 Td
(r,)Tj
0 Tc 0 Tw 0.556 0 Td
( second administration, baseline-correcte)Tj
18.232 0 Td
(d)Tj
-36.021 -1.111 Td
(C1: Epinephrine 0.5 mg IM, manual syringe, first administration, unadjus\
te)Tj
32.795 0 Td
(d)Tj
-32.795 -1.111 Td
(C1: Epinephrine 0.5 mg IM, manual syringe, first administration, baselin\
e-correcte)Tj
36.129 0 Td
(d)Tj
-36.129 -1.111 Td
(C2: Epinephrine 0.5 mg IM, manual syringe, second administration, unadju\
ste)Tj
34.409 0 Td
(d)Tj
-34.409 -1.111 Td
(C2: Epinephrine 0.5 mg IM, manual syringe, second administration, baseli\
ne-correcte)Tj
37.743 0 Td
(d)Tj
6 0 0 6 1514.2919 616.0399 Tm
(180)Tj
2.589 0 Td
(210)Tj
2.589 0 Td
(240)Tj
2.589 0 Td
(270)Tj
2.589 0 Td
(300)Tj
2.589 0 Td
(330)Tj
2.589 0 Td
(360)Tj
-33.67 -22.642 Td
(\0373)Tj
1.463 Tc -1.463 Tw (00)Tj
0 Tc 0 Tw 5.47 0 Td
(30)Tj
2.589 0 Td
(60)Tj
2.589 0 Td
(90)Tj
2.311 0 Td
(120)Tj
2.589 0 Td
(150)Tj
2.589 0 Td
(180)Tj
2.589 0 Td
(210)Tj
2.589 0 Td
(240)Tj
2.589 0 Td
(270)Tj
2.589 0 Td
(300)Tj
2.589 0 Td
(330)Tj
2.589 0 Td
(360)Tj
ET
q 1 0 0 1 1409.2872 653.3821 cm
0 0 m
0 -28.923 l
203.209 -28.923 l
S
Q
BT
6 0 0 6 1395.1661 729.3533 Tm
(120)Tj
0 -1.85 Td
(110)Tj
0 -1.85 Td
(100)Tj
0.556 -1.85 Td
(90)Tj
0 -1.85 Td
(80)Tj
0 -1.85 Td
(70)Tj
0 -1.85 Td
(60)Tj
0 -2.794 Td
(10)Tj
0.556 -1.85 Td
(0)Tj
-1.14 -1.85 Td
(\0371)Tj
(0)Tj
ET
q
1371.633 467.497 250.058 285.953 re
W n
1 0.6 0 0 k
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f
Q
1 0.6 0 0 K
0.7 w 0 J
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0.579 2.099 1.049 1.628 1.049 1.049 c
1.049 0.471 0.579 0 0 0 c
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0.745 -2.698 1.349 -2.094 1.349 -1.349 c
1.349 -0.604 0.745 0 0 0 c
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[2.309 0.462]0 d
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0 0 m
5.311 0 l
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[]0 d
q 1 0 0 1 1424.5034 705.7966 cm
0 0 m
1.25 0 l
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Q
0 0 0 0 k
q 1 0 0 1 1421.5016 704.7473 cm
0 0 m
-0.579 0 -1.049 0.471 -1.049 1.049 c
-1.049 1.628 -0.579 2.099 0 2.099 c
0.579 2.099 1.049 1.628 1.049 1.049 c
1.049 0.471 0.579 0 0 0 c
f
Q
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q 1 0 0 1 1421.5016 707.1458 cm
0 0 m
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0.745 -2.698 1.349 -2.094 1.349 -1.349 c
1.349 -0.604 0.745 0 0 0 c
0 -0.6 m
0.413 -0.6 0.749 -0.936 0.749 -1.349 c
0.749 -1.762 0.413 -2.098 0 -2.098 c
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f
Q
Q
BT
0 6 -6 0 1382.8278 518.964 Tm
(Heart Rate \(bpm)Tj
7.392 0 Td
(\))Tj
ET
q
1371.633 467.497 250.058 285.953 re
W n
q 1 0 0 1 1410.5626 485.77 cm
0 0 m
0 2.834 l
15.534 0 m
15.534 2.834 l
31.067 0 m
31.067 2.834 l
46.6 0 m
46.6 2.834 l
62.134 0 m
62.134 2.834 l
77.667 0 m
77.667 2.834 l
93.2 0 m
93.2 2.834 l
108.733 0 m
108.733 2.834 l
124.266 0 m
124.266 2.834 l
139.801 0 m
139.801 2.834 l
155.334 0 m
155.334 2.834 l
170.867 0 m
170.867 2.834 l
186.4 0 m
186.4 2.834 l
201.933 0 m
201.933 2.834 l
S
Q
Q
BT
-0.037 Tc 0.037 Tw 6 0 0 6 1491.6368 472.9709 Tm
(Ti)Tj
0 Tc 0 Tw 0.796 0 Td
(me \(minutes)Tj
(\))Tj
/T1_1 1 Tf
7 0 0 7 1379.3302 604.1439 Tm
(B. Part )Tj
(2)Tj
ET
q
1371.633 467.497 250.058 285.953 re
W n
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0 0 m
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203.209 -28.74 l
0 78.333 m
0 5.926 l
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0.7 w 0 J
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0 0 m
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S
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0.41 0.5 0.09 0.06 k
1422.851 729.544 -2.698 2.699 re
f
q 1 0 0 1 1417.2495 720.7903 cm
0 0 m
1.25 0 l
S
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0 0 m
5.311 0 l
S
Q
[]0 d
q 1 0 0 1 1424.5034 720.7903 cm
0 0 m
1.25 0 l
S
Q
0 0 0 0 k
1420.452 721.968 2.099 -2.099 re
f
0.41 0.5 0.09 0.06 k
1422.851 722.268 -2.698 -2.699 re
1422.251 720.17 -1.499 1.498 re
f
0.15 0.415 0.5 0 K
q 1 0 0 1 1417.2495 710.8162 cm
0 0 m
8.504 0 l
S
Q
0.15 0.415 0.5 0 k
1422.851 709.467 -2.698 2.699 re
f
q 1 0 0 1 1417.2495 700.6487 cm
0 0 m
1.25 0 l
S
Q
[2.309 0.462]0 d
q 1 0 0 1 1418.9614 700.6487 cm
0 0 m
5.311 0 l
S
Q
[]0 d
q 1 0 0 1 1424.5034 700.6487 cm
0 0 m
1.25 0 l
S
Q
0 0 0 0 k
1420.452 701.826 2.099 -2.099 re
f
0.15 0.415 0.5 0 k
1422.851 702.127 -2.698 -2.699 re
1422.251 700.028 -1.499 1.498 re
f
0.6 0.36 0 0 K
q 1 0 0 1 1417.2495 740.9319 cm
0 0 m
8.504 0 l
S
Q
0.6 0.36 0 0 k
1422.851 739.583 -2.698 2.698 re
f
Q
BT
/T1_0 1 Tf
4.5 0 0 4.5 1427.3906 604.507 Tm
(D: Epinephrine 2 x 6.6 mg IN, opposite nostrils, unadjuste)Tj
25.515 0 Td
(d)Tj
-25.515 -1.111 Td
(D: Epinephrine 2 x 6.6 mg IN, opposite nostrils, baseline-correcte)Tj
28.849 0 Td
(d)Tj
-28.849 -1.111 Td
(E: Epinephrine 2 x 6.6 mg IN, same nostril, unadjuste)Tj
23.624 0 Td
(d)Tj
-23.624 -1.111 Td
(E: Epinephrine 2 x 6.6 mg IN, same nostril, baseline-correcte)Tj
26.958 0 Td
(d)Tj
-26.958 -1.111 Td
(F: Epinephrine 2 x 0.3 mg IM, autoinjecto)Tj
-0.055 Tc 0.055 Tw 18.233 0 Td
(r,)Tj
0 Tc 0 Tw 0.556 0 Td
( opposite thighs, unadjuste)Tj
11.898 0 Td
(d)Tj
-30.687 -1.111 Td
(F: Epinephrine 2 x 0.3 mg IM, autoinjecto)Tj
-0.055 Tc 0.055 Tw 18.233 0 Td
(r,)Tj
0 Tc 0 Tw 0.556 0 Td
( opposite thighs, baseline-correcte)Tj
15.232 0 Td
(d)Tj
ET
q
1371.633 467.497 250.058 285.953 re
W n
q 1 0 0 1 1409.2872 659.2122 cm
0 0 m
0 72.319 l
-2.767 -1.759 m
2.766 1.26 l
-2.767 -7.339 m
2.766 -4.32 l
-2.835 -147.201 m
0 -147.201 l
-2.835 -158.267 m
0 -158.267 l
-2.835 -169.331 m
0 -169.331 l
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-2.698 0.745 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.745 0 0 c
f
Q
q 1 0 0 1 1474.0455 686.4446 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.745 0 0 c
f
Q
q 1 0 0 1 1489.5789 683.304 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.745 0 0 c
f
Q
q 1 0 0 1 1520.6459 681.9548 cm
0 0 m
0 -0.745 -0.605 -1.349 -1.35 -1.349 c
-2.095 -1.349 -2.699 -0.745 -2.699 0 c
-2.699 0.745 -2.095 1.349 -1.35 1.349 c
-0.605 1.349 0 0.745 0 0 c
f
Q
q 1 0 0 1 1613.8459 677.991 cm
0 0 m
0 -0.745 -0.605 -1.349 -1.35 -1.349 c
-2.095 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.095 1.349 -1.35 1.349 c
-0.605 1.349 0 0.745 0 0 c
f
Q
1 0.6 0 0 K
[]0 d
q 1 0 0 1 1612.4958 677.991 cm
0 0 m
-93.2 3.964 l
-124.266 5.313 l
-139.799 8.454 l
-155.333 8.789 l
-163.008 8.789 l
-170.867 10.753 l
-173.534 8.454 l
-175.948 8.789 l
-178.646 11.152 l
-181.058 11.722 l
-183.756 9.803 l
-185.849 13.071 l
-184.842 7.104 l
-186.4 4.205 l
S
Q
0.6 0.36 0 0 k
1427.973 644.191 -2.699 2.699 re
f
1429.862 641.099 -2.698 2.699 re
f
1432.561 642.842 -2.699 2.698 re
f
1435.069 642.292 -2.699 2.699 re
f
1428.885 638.008 -2.698 2.698 re
f
1427.445 635.309 -2.699 2.699 re
f
1437.767 639.912 -2.698 2.699 re
f
1440.275 639.357 -2.699 2.699 re
f
1442.979 641.865 -2.699 2.698 re
f
1450.745 639.912 -2.698 2.699 re
f
1458.512 639.75 -2.699 2.699 re
f
1474.046 639.372 -2.699 2.699 re
f
1489.578 635.998 -2.698 2.699 re
f
1520.646 635.002 -2.699 2.699 re
f
1613.846 630.966 -2.699 2.698 re
f
0.6 0.36 0 0 K
q 1 0 0 1 1612.4958 632.3149 cm
0 0 m
-93.2 4.036 l
-124.267 5.032 l
-139.799 8.406 l
-155.333 8.784 l
-163.1 8.946 l
-170.867 10.899 l
-173.57 8.391 l
S
Q
Q
BT
/GS1 gs
/TT1 1 Tf
4.75 0 0 4.75 1371.4609 459.5613 Tm
(Bpm, beats per minute; IM, intramuscular; IN, intranasal. )Tj
ET
0.6 0 0.06 0 K
0.293 w 0 J
/GS2 gs
q 1 0 0 1 1621.8375 138.4429 cm
0 0 m
0 285.954 l
S
Q
0.241 w
q 1 0 0 1 1371.2882 424.5173 cm
0 0 m
250.696 0 l
S
Q
q 1 0 0 1 1371.2882 138.3221 cm
0 0 m
250.696 0 l
S
Q
0.346 w
q 1 0 0 1 1371.4609 138.4429 cm
0 0 m
0 285.954 l
S
Q
BT
1 0.8 0.38 0.29 k
/GS0 gs
/TT0 1 Tf
6 0 0 6 1371.4609 435.7693 Tm
[(Figure 4. Unadjusted and Baseline-Corrected Mean Systolic Blood P)27.5 (r)25.8 (e)25.9 (s)25.8 (s)25.9 (u)26.1 (r)25.9 (e)25.8 (\226)25.9 (T)43.7 (i)26.2 (m)25.8 (e )]TJ
-0.026 Tc 0 -1.167 Td
[(Profiles )36.8 (After Epinephrine IN or IM in Part 1 \(A\) and Part 2 \(B\))]TJ
ET
/PlacedGraphic /MC1 BDC
EMC
BT
0 0 0 1 k
/T1_2 1 Tf
0 Tc 0 6 -6 0 1382.875 306.0064 Tm
(Systolic Blood Pressure \(mmHg\))Tj
ET
0 0 0 1 K
0.5 w 2 J
q 1 0 0 1 1406.4995 323.6668 cm
0 0 m
2.835 0 l
0 -13.286 m
2.835 -13.286 l
0 -26.572 m
2.835 -26.572 l
0 79.225 m
2.835 79.225 l
0 64.296 m
2.835 64.296 l
0 49.367 m
2.835 49.367 l
0 34.438 m
2.835 34.438 l
0 19.509 m
2.835 19.509 l
4.11 -30.682 m
4.11 -27.847 l
19.644 -30.682 m
19.644 -27.847 l
35.177 -30.682 m
35.177 -27.847 l
50.71 -30.682 m
50.71 -27.847 l
66.244 -30.682 m
66.244 -27.847 l
81.778 -30.682 m
81.778 -27.847 l
97.311 -30.682 m
97.311 -27.847 l
112.844 -30.682 m
112.844 -27.847 l
128.377 -30.682 m
128.377 -27.847 l
143.912 -30.682 m
143.912 -27.847 l
159.445 -30.682 m
159.445 -27.847 l
174.978 -30.682 m
174.978 -27.847 l
190.511 -30.682 m
190.511 -27.847 l
206.044 -30.682 m
206.044 -27.847 l
S
Q
BT
6 0 0 6 1405.521 287.4004 Tm
(\0373)Tj
1.463 Tc -1.463 Tw (00)Tj
0 Tc 0 Tw 5.47 0 Td
(30)Tj
2.589 0 Td
(60)Tj
2.589 0 Td
(90)Tj
2.311 0 Td
(120)Tj
2.589 0 Td
(150)Tj
/T1_3 1 Tf
7 0 0 7 1379.3774 415.1853 Tm
(A. Part )Tj
(1)Tj
/T1_2 1 Tf
4.5 0 0 4.5 1427.438 415.6106 Tm
(A: Epinephrine 6.6 mg IN, unadjuste)Tj
16.066 0 Td
(d)Tj
-16.066 -1.111 Td
(A: Epinephrine 6.6 mg IN, baseline-correcte)Tj
19.399 0 Td
(d)Tj
-19.399 -1.111 Td
(B1: Epinephrine 0.3 mg IM, autoinjecto)Tj
-0.055 Tc 0.055 Tw 17.233 0 Td
(r,)Tj
0 Tc 0 Tw 0.556 0 Td
( first administration, unadjuste)Tj
13.285 0 Td
(d)Tj
-31.073 -1.111 Td
(B1: Epinephrine 0.3 mg IM, autoinjecto)Tj
-0.055 Tc 0.055 Tw 17.233 0 Td
(r,)Tj
0 Tc 0 Tw 0.556 0 Td
( first administration, baseline-correcte)Tj
16.618 0 Td
(d)Tj
-34.407 -1.111 Td
(B2: Epinephrine 0.3 mg IM, autoinjecto)Tj
-0.055 Tc 0.055 Tw 17.233 0 Td
(r,)Tj
0 Tc 0 Tw 0.556 0 Td
( second administration, unadjuste)Tj
14.899 0 Td
(d)Tj
-32.687 -1.111 Td
(B2: Epinephrine 0.3 mg IM, autoinjecto)Tj
-0.055 Tc 0.055 Tw 17.233 0 Td
(r,)Tj
0 Tc 0 Tw 0.556 0 Td
( second administration, baseline-correcte)Tj
18.232 0 Td
(d)Tj
-36.021 -1.111 Td
(C1: Epinephrine 0.5 mg IM, manual syringe, first administration, unadjus\
te)Tj
32.795 0 Td
(d)Tj
-32.795 -1.111 Td
(C1: Epinephrine 0.5 mg IM, manual syringe, first administration, baselin\
e-correcte)Tj
36.129 0 Td
(d)Tj
-36.129 -1.111 Td
(C2: Epinephrine 0.5 mg IM, manual syringe, second administration, unadju\
ste)Tj
34.409 0 Td
(d)Tj
-34.409 -1.111 Td
(C2: Epinephrine 0.5 mg IM, manual syringe, second administration, baseli\
ne-correcte)Tj
37.743 0 Td
(d)Tj
6 0 0 6 1514.3391 287.4004 Tm
(180)Tj
2.589 0 Td
(210)Tj
2.589 0 Td
(240)Tj
2.589 0 Td
(270)Tj
2.589 0 Td
(300)Tj
2.589 0 Td
(330)Tj
2.589 0 Td
(360)Tj
-33.67 -22.642 Td
(\0373)Tj
1.463 Tc -1.463 Tw (00)Tj
0 Tc 0 Tw 5.47 0 Td
(30)Tj
2.589 0 Td
(60)Tj
2.589 0 Td
(90)Tj
2.311 0 Td
(120)Tj
2.589 0 Td
(150)Tj
2.589 0 Td
(180)Tj
2.589 0 Td
(210)Tj
2.589 0 Td
(240)Tj
2.589 0 Td
(270)Tj
2.589 0 Td
(300)Tj
2.589 0 Td
(330)Tj
2.589 0 Td
(360)Tj
ET
q 1 0 0 1 1409.3345 330.1741 cm
0 0 m
0 -34.355 l
203.209 -34.355 l
S
Q
BT
6 0 0 6 1395.2134 400.7137 Tm
(150)Tj
0 -2.467 Td
(140)Tj
0 -2.467 Td
(130)Tj
0 -2.467 Td
(120)Tj
0 -2.467 Td
(110)Tj
0.556 -3.307 Td
(10)Tj
0.556 -2.208 Td
(0)Tj
-1.14 -2.208 Td
(\0371)Tj
(0)Tj
0.584 -18.319 Td
(10)Tj
0.556 -2.208 Td
(0)Tj
-1.14 -2.208 Td
(\0371)Tj
(0)Tj
ET
q
1371.633 138.442 250.058 285.954 re
W n
1 0.6 0 0 k
q 1 0 0 1 1422.8979 417.3113 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.745 0 0 c
f
Q
1 0.6 0 0 K
0.7 w 0 J
q 1 0 0 1 1417.2969 417.3113 cm
0 0 m
8.504 0 l
S
Q
0.82 1 0.18 0.12 k
q 1 0 0 1 1422.8979 407.2728 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.745 0 0 c
f
Q
0.82 1 0.18 0.12 K
q 1 0 0 1 1417.2969 407.2728 cm
0 0 m
8.504 0 l
S
Q
0.3 0.83 1 0 k
q 1 0 0 1 1422.8979 387.1956 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.745 0 0 c
f
Q
0.3 0.83 1 0 K
q 1 0 0 1 1417.2969 387.1956 cm
0 0 m
8.504 0 l
S
Q
0.82 1 0.18 0.12 K
q 1 0 0 1 1417.2969 397.2342 cm
0 0 m
1.25 0 l
S
Q
[2.309 0.462]0 d
q 1 0 0 1 1419.0088 397.2342 cm
0 0 m
5.311 0 l
S
Q
[]0 d
q 1 0 0 1 1424.5508 397.2342 cm
0 0 m
1.25 0 l
S
Q
0 0 0 0 k
q 1 0 0 1 1421.5488 396.1849 cm
0 0 m
-0.579 0 -1.049 0.471 -1.049 1.049 c
-1.049 1.628 -0.579 2.099 0 2.099 c
0.579 2.099 1.049 1.628 1.049 1.049 c
1.049 0.471 0.579 0 0 0 c
f
Q
0.82 1 0.18 0.12 k
q 1 0 0 1 1421.5488 398.5833 cm
0 0 m
-0.745 0 -1.349 -0.604 -1.349 -1.349 c
-1.349 -2.094 -0.745 -2.698 0 -2.698 c
0.745 -2.698 1.349 -2.094 1.349 -1.349 c
1.349 -0.604 0.745 0 0 0 c
0 -0.6 m
0.413 -0.6 0.749 -0.936 0.749 -1.349 c
0.749 -1.762 0.413 -2.098 0 -2.098 c
-0.413 -2.098 -0.749 -1.762 -0.749 -1.349 c
-0.749 -0.936 -0.413 -0.6 0 -0.6 c
f
Q
0.3 0.83 1 0 K
q 1 0 0 1 1417.2969 377.157 cm
0 0 m
1.25 0 l
S
Q
[2.309 0.462]0 d
q 1 0 0 1 1419.0088 377.157 cm
0 0 m
5.311 0 l
S
Q
[]0 d
q 1 0 0 1 1424.5508 377.157 cm
0 0 m
1.25 0 l
S
Q
0 0 0 0 k
q 1 0 0 1 1421.5488 376.1077 cm
0 0 m
-0.579 0 -1.049 0.471 -1.049 1.049 c
-1.049 1.628 -0.579 2.099 0 2.099 c
0.579 2.099 1.049 1.628 1.049 1.049 c
1.049 0.471 0.579 0 0 0 c
f
Q
0.3 0.83 1 0 k
q 1 0 0 1 1421.5488 378.5062 cm
0 0 m
-0.745 0 -1.349 -0.604 -1.349 -1.349 c
-1.349 -2.094 -0.745 -2.698 0 -2.698 c
0.745 -2.698 1.349 -2.094 1.349 -1.349 c
1.349 -0.604 0.745 0 0 0 c
0 -0.6 m
0.413 -0.6 0.749 -0.936 0.749 -1.349 c
0.749 -1.762 0.413 -2.098 0 -2.098 c
-0.413 -2.098 -0.749 -1.762 -0.749 -1.349 c
-0.749 -0.936 -0.413 -0.6 0 -0.6 c
f
Q
Q
BT
0 6 -6 0 1382.875 170.1534 Tm
(Systolic Blood Pressure \(mmHg\))Tj
ET
q
1371.633 138.442 250.058 285.954 re
W n
q 1 0 0 1 1406.4995 267.0374 cm
0 0 m
2.835 0 l
0 -14.884 m
2.835 -14.884 l
0 -29.769 m
2.835 -29.769 l
0 -44.654 m
2.835 -44.654 l
0 -59.539 m
2.835 -59.539 l
0 -79.38 m
2.835 -79.38 l
0 -92.626 m
2.835 -92.626 l
0 -105.873 m
2.835 -105.873 l
4.11 -109.907 m
4.11 -107.073 l
19.644 -109.907 m
19.644 -107.073 l
35.177 -109.907 m
35.177 -107.073 l
50.71 -109.907 m
50.71 -107.073 l
66.244 -109.907 m
66.244 -107.073 l
81.778 -109.907 m
81.778 -107.073 l
97.311 -109.907 m
97.311 -107.073 l
112.844 -109.907 m
112.844 -107.073 l
128.377 -109.907 m
128.377 -107.073 l
143.912 -109.907 m
143.912 -107.073 l
159.445 -109.907 m
159.445 -107.073 l
174.978 -109.907 m
174.978 -107.073 l
190.511 -109.907 m
190.511 -107.073 l
206.044 -109.907 m
206.044 -107.073 l
S
Q
Q
BT
-0.037 Tc 0.037 Tw 6 0 0 6 1491.6841 144.3314 Tm
(Ti)Tj
0 Tc 0 Tw 0.796 0 Td
(me \(minutes)Tj
(\))Tj
/T1_3 1 Tf
7 0 0 7 1379.3774 275.5044 Tm
(B. Part )Tj
(2)Tj
ET
q
1371.633 138.442 250.058 285.954 re
W n
q 1 0 0 1 1409.3345 194.3083 cm
0 0 m
0 -34.344 l
203.209 -34.344 l
S
Q
Q
BT
/T1_2 1 Tf
6 0 0 6 1395.2134 264.8594 Tm
(150)Tj
0 -2.467 Td
(140)Tj
0 -2.467 Td
(130)Tj
0 -2.467 Td
(120)Tj
0 -2.467 Td
(110)Tj
ET
q
1371.633 138.442 250.058 285.954 re
W n
0.41 0.5 0.09 0.06 K
0.7 w 0 J
q 1 0 0 1 1417.2969 402.2537 cm
0 0 m
8.504 0 l
S
Q
0.41 0.5 0.09 0.06 k
1422.898 400.904 -2.698 2.699 re
f
q 1 0 0 1 1417.2969 392.1507 cm
0 0 m
1.25 0 l
S
Q
[2.309 0.462]0 d
q 1 0 0 1 1419.0088 392.1507 cm
0 0 m
5.311 0 l
S
Q
[]0 d
q 1 0 0 1 1424.5508 392.1507 cm
0 0 m
1.25 0 l
S
Q
0 0 0 0 k
1420.5 393.328 2.099 -2.099 re
f
0.41 0.5 0.09 0.06 k
1422.898 393.629 -2.698 -2.699 re
1422.298 391.53 -1.499 1.498 re
f
0.15 0.415 0.5 0 K
q 1 0 0 1 1417.2969 382.1766 cm
0 0 m
8.504 0 l
S
Q
0.15 0.415 0.5 0 k
1422.898 380.827 -2.698 2.699 re
f
q 1 0 0 1 1417.2969 372.0091 cm
0 0 m
1.25 0 l
S
Q
[2.309 0.462]0 d
q 1 0 0 1 1419.0088 372.0091 cm
0 0 m
5.311 0 l
S
Q
[]0 d
q 1 0 0 1 1424.5508 372.0091 cm
0 0 m
1.25 0 l
S
Q
0 0 0 0 k
1420.5 373.187 2.099 -2.099 re
f
0.15 0.415 0.5 0 k
1422.898 373.487 -2.698 -2.699 re
1422.298 371.388 -1.499 1.498 re
f
0.6 0.36 0 0 K
q 1 0 0 1 1417.2969 412.2923 cm
0 0 m
8.504 0 l
S
Q
0.6 0.36 0 0 k
1422.898 410.943 -2.698 2.698 re
f
Q
BT
4.5 0 0 4.5 1427.438 275.8673 Tm
(D: Epinephrine 2 x 6.6 mg IN, opposite nostrils, unadjuste)Tj
25.515 0 Td
(d)Tj
-25.515 -1.111 Td
(D: Epinephrine 2 x 6.6 mg IN, opposite nostrils, baseline-correcte)Tj
28.849 0 Td
(d)Tj
-28.849 -1.111 Td
(E: Epinephrine 2 x 6.6 mg IN, same nostril, unadjuste)Tj
23.624 0 Td
(d)Tj
-23.624 -1.111 Td
(E: Epinephrine 2 x 6.6 mg IN, same nostril, baseline-correcte)Tj
26.958 0 Td
(d)Tj
-26.958 -1.111 Td
(F: Epinephrine 2 x 0.3 mg IM, autoinjecto)Tj
-0.055 Tc 0.055 Tw 18.233 0 Td
(r,)Tj
0 Tc 0 Tw 0.556 0 Td
( opposite thighs, unadjuste)Tj
11.898 0 Td
(d)Tj
-30.687 -1.111 Td
(F: Epinephrine 2 x 0.3 mg IM, autoinjecto)Tj
-0.055 Tc 0.055 Tw 18.233 0 Td
(r,)Tj
0 Tc 0 Tw 0.556 0 Td
( opposite thighs, baseline-correcte)Tj
15.232 0 Td
(d)Tj
ET
q
1371.633 138.442 250.058 285.954 re
W n
q 1 0 0 1 1409.3345 336.7518 cm
0 0 m
0 66.14 l
0 -135.793 m
0 -69.714 l
-2.767 -1.509 m
2.766 1.51 l
-2.767 -8.087 m
2.766 -5.068 l
-2.767 -137.524 m
2.766 -134.505 l
-2.767 -143.833 m
2.766 -140.813 l
S
Q
1 0.8 0.38 0.29 K
0.7 w 0 J
q 1 0 0 1 1417.2969 277.5684 cm
0 0 m
8.504 0 l
S
Q
0.13 0.8 0 0 K
q 1 0 0 1 1417.2969 267.5294 cm
0 0 m
8.504 0 l
S
Q
0.57 0 1 0 K
q 1 0 0 1 1417.2969 257.5223 cm
0 0 m
8.504 0 l
S
Q
1 0.8 0.38 0.29 k
q 1 0 0 1 1422.8979 277.5674 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.745 0 0 c
f
Q
0.13 0.8 0 0 k
q 1 0 0 1 1422.8979 267.5294 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.745 0 0 c
f
Q
0.57 0 1 0 k
q 1 0 0 1 1422.8979 257.5223 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.745 0 0 c
f
Q
0.4 0.32 0.152 0.116 K
q 1 0 0 1 1417.2969 272.5484 cm
0 0 m
8.504 0 l
S
Q
0.4 0.32 0.152 0.116 k
1422.898 271.199 -2.698 2.698 re
f
0.078 0.48 0 0 K
q 1 0 0 1 1417.2969 262.5094 cm
0 0 m
8.504 0 l
S
Q
0.078 0.48 0 0 k
1422.898 261.161 -2.698 2.698 re
f
0.342 0 0.6 0 K
q 1 0 0 1 1417.2969 252.4074 cm
0 0 m
8.504 0 l
S
Q
0.342 0 0.6 0 k
1422.898 251.057 -2.698 2.698 re
f
0.57 0 1 0 k
q 1 0 0 1 1411.959 229.6964 cm
0 0 m
0 -0.745 -0.604 -1.35 -1.349 -1.35 c
-2.094 -1.35 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.348 -1.349 1.348 c
-0.604 1.348 0 0.745 0 0 c
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-183.983 -15.981 l
-184.96 -13.021 l
-185.872 -8.939 l
-186.4 -7.833 l
S
Q
Q
BT
/GS1 gs
/TT1 1 Tf
4.75 0 0 4.75 1371.4609 130.5077 Tm
(IM, intramuscular; IN, intranasal. )Tj
ET
0.6 0 0.06 0 K
0.293 w 0 J
/GS2 gs
q 1 0 0 1 1086.4297 278.196 cm
0 0 m
0 304.379 l
S
Q
0.241 w
q 1 0 0 1 835.8803 582.6957 cm
0 0 m
250.696 0 l
S
Q
q 1 0 0 1 835.8803 278.0753 cm
0 0 m
250.696 0 l
S
Q
0.346 w
q 1 0 0 1 836.053 278.196 cm
0 0 m
0 304.379 l
S
Q
BT
1 0.8 0.38 0.29 k
/GS0 gs
/TT0 1 Tf
6 0 0 6 836.053 593.9476 Tm
[(Figure 2. Median Baseline-Corrected Plasma Concentration\226T)17.8 (ime Profiles )36.8 (After )]TJ
0 -1.167 Td
(Epinephrine IN or IM in Part 1 \(A\) and Part 2 \(B\))Tj
ET
/PlacedGraphic /MC2 BDC
EMC
BT
0 0 0 1 k
/T1_4 1 Tf
0 6 -6 0 847.3276 479.0028 Tm
(Plasma Epinephrine)Tj
-0.5 -1.2 Td
(Concentration \(pg/mL)Tj
9.616 0 Td
(\))Tj
ET
0 0 0 1 K
0.5 w 2 J
q 1 0 0 1 870.9521 559.3931 cm
0 0 m
2.835 0 l
0 -15.114 m
2.835 -15.114 l
0 -30.228 m
2.835 -30.228 l
0 -45.342 m
2.835 -45.342 l
0 -60.456 m
2.835 -60.456 l
0 -75.569 m
2.835 -75.569 l
0 -90.683 m
2.835 -90.683 l
0 -105.797 m
2.835 -105.797 l
4.11 -109.907 m
4.11 -107.072 l
20.938 -109.907 m
20.938 -107.072 l
37.766 -109.907 m
37.766 -107.072 l
54.594 -109.907 m
54.594 -107.072 l
71.422 -109.907 m
71.422 -107.072 l
88.25 -109.907 m
88.25 -107.072 l
105.078 -109.907 m
105.078 -107.072 l
121.906 -109.907 m
121.906 -107.072 l
138.733 -109.907 m
138.733 -107.072 l
155.561 -109.907 m
155.561 -107.072 l
172.389 -109.907 m
172.389 -107.072 l
189.216 -109.907 m
189.216 -107.072 l
206.044 -109.907 m
206.044 -107.072 l
S
Q
BT
2.249 Tc -2.249 Tw 6 0 0 6 873.3936 443.9017 Tm
(05)Tj
0 Tc 0 Tw 5.331 0 Td
(10)Tj
2.805 0 Td
(15)Tj
2.805 0 Td
(20)Tj
2.805 0 Td
(25)Tj
2.805 0 Td
(30)Tj
-0.037 Tc 0.037 Tw -2.759 -1.202 Td
(Ti)Tj
0 Tc 0 Tw 0.796 0 Td
(me \(minutes)Tj
5.501 0 Td
(\))Tj
/T1_5 1 Tf
7 0 0 7 843.83 573.3877 Tm
(A. Part )Tj
(1)Tj
/T1_4 1 Tf
4.5 0 0 4.5 891.8905 573.8126 Tm
(A: Epinephrine 6.6 mg IN)Tj
0 -1.111 Td
(B1: Epinephrine 0.3 mg IM, autoinjecto)Tj
-0.055 Tc 0.055 Tw 17.233 0 Td
(r,)Tj
0 Tc 0 Tw 0.556 0 Td
( first administration)Tj
-17.789 -1.111 Td
(B2: Epinephrine 0.3 mg IM, autoinjecto)Tj
-0.055 Tc 0.055 Tw 17.233 0 Td
(r,)Tj
0 Tc 0 Tw 0.556 0 Td
( second administration)Tj
-17.789 -1.111 Td
(C1: Epinephrine 0.5 mg IM, manual syringe, first administration)Tj
0 -1.111 Td
(C2: Epinephrine 0.5 mg IM, manual syringe, second administration)Tj
6 0 0 6 989.5197 443.9017 Tm
(35)Tj
2.805 0 Td
(40)Tj
2.805 0 Td
(45)Tj
2.805 0 Td
(50)Tj
2.805 0 Td
(55)Tj
2.804 0 Td
(60)Tj
ET
q 1 0 0 1 873.787 559.3931 cm
0 0 m
0 -107.072 l
203.209 -107.072 l
S
Q
BT
6 0 0 6 859.6659 557.2148 Tm
(700)Tj
0 -2.517 Td
(600)Tj
0 -2.517 Td
(500)Tj
0 -2.517 Td
(400)Tj
0 -2.517 Td
(300)Tj
0 -2.517 Td
(200)Tj
0 -2.517 Td
(100)Tj
1.112 -2.517 Td
(0)Tj
ET
q
836.226 278.196 250.057 304.378 re
W n
1 0.6 0 0 k
q 1 0 0 1 887.3505 575.5137 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.745 0 0 c
f
Q
1 0.6 0 0 K
0.7 w 0 J
q 1 0 0 1 881.7494 575.5137 cm
0 0 m
8.504 0 l
S
Q
0.82 1 0.18 0.12 k
q 1 0 0 1 887.3505 570.4648 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.745 0 0 c
f
Q
0.82 1 0.18 0.12 K
q 1 0 0 1 881.7494 570.4648 cm
0 0 m
8.504 0 l
S
Q
0.3 0.83 1 0 k
q 1 0 0 1 887.3505 560.3668 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.745 0 0 c
f
Q
0.3 0.83 1 0 K
q 1 0 0 1 881.7494 560.3668 cm
0 0 m
8.504 0 l
S
Q
0.82 1 0.18 0.12 K
q 1 0 0 1 881.7494 565.416 cm
0 0 m
1.25 0 l
S
Q
[2.309 0.462]0 d
q 1 0 0 1 883.4613 565.416 cm
0 0 m
5.311 0 l
S
Q
[]0 d
q 1 0 0 1 889.0033 565.416 cm
0 0 m
1.25 0 l
S
Q
0 0 0 0 k
q 1 0 0 1 886.0014 564.3662 cm
0 0 m
-0.579 0 -1.049 0.471 -1.049 1.049 c
-1.049 1.628 -0.579 2.099 0 2.099 c
0.579 2.099 1.049 1.628 1.049 1.049 c
1.049 0.471 0.579 0 0 0 c
f
Q
0.82 1 0.18 0.12 k
q 1 0 0 1 886.0014 566.7651 cm
0 0 m
-0.745 0 -1.349 -0.604 -1.349 -1.349 c
-1.349 -2.094 -0.745 -2.698 0 -2.698 c
0.745 -2.698 1.349 -2.094 1.349 -1.349 c
1.349 -0.604 0.745 0 0 0 c
0 -0.6 m
0.413 -0.6 0.749 -0.936 0.749 -1.349 c
0.749 -1.762 0.413 -2.099 0 -2.099 c
-0.413 -2.099 -0.749 -1.762 -0.749 -1.349 c
-0.749 -0.936 -0.413 -0.6 0 -0.6 c
f
Q
0.3 0.83 1 0 K
q 1 0 0 1 881.7494 555.3179 cm
0 0 m
1.25 0 l
S
Q
[2.309 0.462]0 d
q 1 0 0 1 883.4613 555.3179 cm
0 0 m
5.311 0 l
S
Q
[]0 d
q 1 0 0 1 889.0033 555.3179 cm
0 0 m
1.25 0 l
S
Q
0 0 0 0 k
q 1 0 0 1 886.0014 554.269 cm
0 0 m
-0.579 0 -1.049 0.471 -1.049 1.049 c
-1.049 1.628 -0.579 2.099 0 2.099 c
0.579 2.099 1.049 1.628 1.049 1.049 c
1.049 0.471 0.579 0 0 0 c
f
Q
0.3 0.83 1 0 k
q 1 0 0 1 886.0014 556.6671 cm
0 0 m
-0.745 0 -1.349 -0.604 -1.349 -1.349 c
-1.349 -2.094 -0.745 -2.698 0 -2.698 c
0.745 -2.698 1.349 -2.094 1.349 -1.349 c
1.349 -0.604 0.745 0 0 0 c
0 -0.6 m
0.413 -0.6 0.749 -0.936 0.749 -1.349 c
0.749 -1.762 0.413 -2.098 0 -2.098 c
-0.413 -2.098 -0.749 -1.762 -0.749 -1.349 c
-0.749 -0.936 -0.413 -0.6 0 -0.6 c
f
Q
Q
BT
0 6 -6 0 847.3276 326.5648 Tm
(Plasma Epinephrine)Tj
-0.5 -1.2 Td
(Concentration \(pg/mL)Tj
9.616 0 Td
(\))Tj
ET
q
836.226 278.196 250.057 304.378 re
W n
q 1 0 0 1 870.9521 406.9548 cm
0 0 m
2.835 0 l
0 -15.114 m
2.835 -15.114 l
0 -30.227 m
2.835 -30.227 l
0 -45.341 m
2.835 -45.341 l
0 -60.456 m
2.835 -60.456 l
0 -75.569 m
2.835 -75.569 l
0 -90.683 m
2.835 -90.683 l
0 -105.797 m
2.835 -105.797 l
4.11 -109.907 m
4.11 -107.073 l
20.938 -109.907 m
20.938 -107.073 l
37.766 -109.907 m
37.766 -107.073 l
54.594 -109.907 m
54.594 -107.073 l
71.422 -109.907 m
71.422 -107.073 l
88.25 -109.907 m
88.25 -107.073 l
105.078 -109.907 m
105.078 -107.073 l
121.906 -109.907 m
121.906 -107.073 l
138.733 -109.907 m
138.733 -107.073 l
155.561 -109.907 m
155.561 -107.073 l
172.389 -109.907 m
172.389 -107.073 l
189.216 -109.907 m
189.216 -107.073 l
206.044 -109.907 m
206.044 -107.073 l
S
Q
Q
BT
2.249 Tc -2.249 Tw 6 0 0 6 873.3936 291.4638 Tm
(05)Tj
0 Tc 0 Tw 5.331 0 Td
(10)Tj
2.805 0 Td
(15)Tj
2.805 0 Td
(20)Tj
2.805 0 Td
(25)Tj
2.805 0 Td
(30)Tj
-0.037 Tc 0.037 Tw -2.759 -1.202 Td
(Ti)Tj
0 Tc 0 Tw 0.796 0 Td
(me \(minutes)Tj
5.501 0 Td
(\))Tj
/T1_5 1 Tf
7 0 0 7 843.83 420.9498 Tm
(B. Part )Tj
(2)Tj
/T1_4 1 Tf
4.5 0 0 4.5 891.8905 421.3748 Tm
(D: Epinephrine 2 x 6.6 mg IN, opposite nostrils)Tj
0 -1.111 Td
(E: Epinephrine 2 x 6.6 mg IN, same nostril)Tj
0 -1.111 Td
(F: Epinephrine 2 x 0.3 mg IM, autoinjecto)Tj
-0.055 Tc 0.055 Tw 18.233 0 Td
(r,)Tj
0 Tc 0 Tw 0.556 0 Td
( opposite thighs)Tj
6 0 0 6 989.5197 291.4638 Tm
(35)Tj
2.805 0 Td
(40)Tj
2.805 0 Td
(45)Tj
2.805 0 Td
(50)Tj
2.805 0 Td
(55)Tj
2.804 0 Td
(60)Tj
ET
q
836.226 278.196 250.057 304.378 re
W n
q 1 0 0 1 873.787 406.9548 cm
0 0 m
0 -107.073 l
203.209 -107.073 l
S
Q
Q
BT
6 0 0 6 859.6659 404.7768 Tm
(700)Tj
0 -2.517 Td
(600)Tj
0 -2.517 Td
(500)Tj
0 -2.517 Td
(400)Tj
0 -2.517 Td
(300)Tj
0 -2.517 Td
(200)Tj
0 -2.517 Td
(100)Tj
1.112 -2.517 Td
(0)Tj
ET
q
836.226 278.196 250.057 304.378 re
W n
1 0.8 0.38 0.29 K
0.7 w 0 J
q 1 0 0 1 881.7494 423.0748 cm
0 0 m
8.504 0 l
S
Q
1 0.8 0.38 0.29 k
q 1 0 0 1 887.3505 423.0748 cm
0 0 m
0 -0.745 -0.604 -1.348 -1.349 -1.348 c
-2.094 -1.348 -2.698 -0.745 -2.698 0 c
-2.698 0.746 -2.094 1.35 -1.349 1.35 c
-0.604 1.35 0 0.746 0 0 c
f
Q
0.13 0.8 0 0 K
q 1 0 0 1 881.7494 418.0068 cm
0 0 m
8.504 0 l
S
Q
0.13 0.8 0 0 k
q 1 0 0 1 887.3505 418.0068 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.35 -1.349 1.35 c
-0.604 1.35 0 0.745 0 0 c
f
Q
0.57 0 1 0 K
q 1 0 0 1 881.7494 412.9388 cm
0 0 m
8.504 0 l
S
Q
0.57 0 1 0 k
q 1 0 0 1 887.3505 412.9388 cm
0 0 m
0 -0.745 -0.604 -1.35 -1.349 -1.35 c
-2.094 -1.35 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.348 -1.349 1.348 c
-0.604 1.348 0 0.745 0 0 c
f
Q
Q
q
842.176 281.363 238.157 298.043 re
W n
0.57 0 1 0 K
0.7 w 0 J
q 1 0 0 1 1076.9957 330.2818 cm
0 0 m
-50.483 4.761 l
-100.966 18.835 l
-117.794 16.562 l
-134.622 16.137 l
-151.45 27.325 l
-168.278 29.252 l
-185.105 -2.949 l
-191.804 -18.708 l
-198.607 -26.521 l
-201.933 -29.124 l
S
Q
Q
q
836.226 278.196 250.057 304.378 re
W n
0.57 0 1 0 k
q 1 0 0 1 893.2397 327.3328 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.745 0 0 c
f
Q
q 1 0 0 1 886.5404 311.5738 cm
0 0 m
0 -0.746 -0.604 -1.35 -1.349 -1.35 c
-2.094 -1.35 -2.698 -0.746 -2.698 0 c
-2.698 0.744 -2.094 1.348 -1.349 1.348 c
-0.604 1.348 0 0.744 0 0 c
f
Q
q 1 0 0 1 879.7377 303.7608 cm
0 0 m
0 -0.745 -0.604 -1.35 -1.349 -1.35 c
-2.094 -1.35 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.745 0 0 c
f
Q
q 1 0 0 1 910.0673 359.5338 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.746 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.746 0 0 c
f
Q
q 1 0 0 1 926.8949 357.6068 cm
0 0 m
0 -0.745 -0.604 -1.35 -1.349 -1.35 c
-2.094 -1.35 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.348 -1.349 1.348 c
-0.604 1.348 0 0.745 0 0 c
f
Q
q 1 0 0 1 977.3787 349.1168 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.095 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.746 -2.095 1.349 -1.349 1.349 c
-0.604 1.349 0 0.746 0 0 c
f
Q
q 1 0 0 1 960.5507 346.8438 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.35 -1.349 1.35 c
-0.604 1.35 0 0.745 0 0 c
f
Q
q 1 0 0 1 943.7227 346.4188 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.745 0 0 c
f
Q
q 1 0 0 1 1027.8627 335.0428 cm
0 0 m
0 -0.745 -0.605 -1.348 -1.35 -1.348 c
-2.095 -1.348 -2.699 -0.745 -2.699 0 c
-2.699 0.745 -2.095 1.35 -1.35 1.35 c
-0.605 1.35 0 0.745 0 0 c
f
Q
q 1 0 0 1 1078.3457 330.2818 cm
0 0 m
0 -0.746 -0.605 -1.35 -1.35 -1.35 c
-2.095 -1.35 -2.698 -0.746 -2.698 0 c
-2.698 0.745 -2.095 1.348 -1.35 1.348 c
-0.605 1.348 0 0.745 0 0 c
f
Q
Q
q
842.176 281.363 238.157 298.043 re
W n
0.13 0.8 0 0 K
0.7 w 0 J
q 1 0 0 1 1076.9957 338.8867 cm
0 0 m
-50.483 13.742 l
-100.966 33.572 l
-117.794 50.92 l
-134.622 50.467 l
-151.45 59.991 l
-168.278 56.816 l
-185.105 0.816 l
-191.804 -18.13 l
-198.607 -33.776 l
-201.933 -37.729 l
S
Q
Q
q
836.226 278.196 250.057 304.378 re
W n
0.13 0.8 0 0 k
q 1 0 0 1 1078.3457 338.8867 cm
0 0 m
0 -0.745 -0.605 -1.349 -1.35 -1.349 c
-2.095 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.095 1.35 -1.35 1.35 c
-0.605 1.35 0 0.745 0 0 c
f
Q
q 1 0 0 1 1027.8627 352.6288 cm
0 0 m
0 -0.745 -0.605 -1.349 -1.35 -1.349 c
-2.095 -1.349 -2.699 -0.745 -2.699 0 c
-2.699 0.745 -2.095 1.349 -1.35 1.349 c
-0.605 1.349 0 0.745 0 0 c
f
Q
q 1 0 0 1 977.3787 372.4588 cm
0 0 m
0 -0.744 -0.604 -1.348 -1.349 -1.348 c
-2.095 -1.348 -2.698 -0.744 -2.698 0 c
-2.698 0.745 -2.095 1.35 -1.349 1.35 c
-0.604 1.35 0 0.745 0 0 c
f
Q
q 1 0 0 1 960.5507 389.8068 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.35 -1.349 1.35 c
-0.604 1.35 0 0.745 0 0 c
f
Q
q 1 0 0 1 943.7227 389.3538 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.745 0 0 c
f
Q
q 1 0 0 1 926.8949 398.8777 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.745 0 0 c
f
Q
q 1 0 0 1 910.0673 395.7028 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.746 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.746 0 0 c
f
Q
q 1 0 0 1 893.2397 339.7028 cm
0 0 m
0 -0.745 -0.604 -1.348 -1.349 -1.348 c
-2.094 -1.348 -2.698 -0.745 -2.698 0 c
-2.698 0.746 -2.094 1.35 -1.349 1.35 c
-0.604 1.35 0 0.746 0 0 c
f
Q
q 1 0 0 1 886.5404 320.7568 cm
0 0 m
0 -0.745 -0.604 -1.35 -1.349 -1.35 c
-2.094 -1.35 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.745 0 0 c
f
Q
q 1 0 0 1 879.7377 305.1098 cm
0 0 m
0 -0.745 -0.604 -1.349 -1.349 -1.349 c
-2.094 -1.349 -2.698 -0.745 -2.698 0 c
-2.698 0.745 -2.094 1.349 -1.349 1.349 c
-0.604 1.349 0 0.745 0 0 c
f
Q
Q
q
842.176 281.363 238.157 298.043 re
W n
1 0.8 0.38 0.29 K
0.7 w 0 J
q 1 0 0 1 1076.9957 336.6138 cm
0 0 m
-50.483 0.923 l
-100.966 17.364 l
-117.794 10.335 l
-134.622 9.427 l
-151.45 4.439 l
-168.278 -0.097 l
-185.105 -19.598 l
-191.804 -27.649 l
-198.607 -32.865 l
-201.933 -35.456 l
S
Q
Q
q
836.226 278.196 250.057 304.378 re
W n
1 0.8 0.38 0.29 k
q 1 0 0 1 893.2397 317.0158 cm
0 0 m
0 -0.745 -0.604 -1.35 -1.349 -1.35 c
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S
Q
Q
BT
/GS1 gs
/TT1 1 Tf
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(IM, intramuscular; IN, intranasal.)Tj
ET
0.6 0 0.06 0 k
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568.551 425.407 136.063 -9.921 re
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704.614 415.486 56.942 -9.921 re
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704.614 405.565 56.942 -9.921 re
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568.551 395.643 136.063 -9.921 re
704.614 395.643 56.942 -9.921 re
761.556 395.643 56.942 -9.921 re
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0.6 0 0.06 0 K
0.593 w 0 J
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Q
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S
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BT
1 0.8 0.38 0.29 k
/GS0 gs
/TT0 1 Tf
6 0 0 6 568.5514 462.3325 Tm
[(T)73.9 (able 1. Demographics and Baseline Characteristics for Overall Population\
s in Part 1 )]TJ
0 -1.167 Td
(and Part 2)Tj
0.472 -2.862 Td
(Characteristic)Tj
25.56 1.167 Td
(Part 1)Tj
-0.097 -1.167 Td
(N = 55)Tj
9.588 1.167 Td
(Part 2)Tj
-0.097 -1.167 Td
(N = 40)Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
-34.953 -1.556 Td
(Age \(years\), mean \261 SD)Tj
25.563 0 Td
(33 \261 6)Tj
9.49 0 Td
(31 \261 7)Tj
-35.054 -1.654 Td
(Male, n \(%\))Tj
24.921 0 Td
(44 \(80%\))Tj
9.49 0 Td
(31 \(78%\))Tj
-34.411 -1.654 Td
[(W)17.7 (eight \(kg\), mean \261 SD )]TJ
25.285 0 Td
(83 \261 14)Tj
9.49 0 Td
(77 \261 13)Tj
-34.776 -1.654 Td
(Height \(cm\), mean \261 SD)Tj
25.285 0 Td
(177 \261 9)Tj
9.49 0 Td
(174 \261 8)Tj
/C2_1 1 Tf
-34.776 -1.654 Td
<00250030002C0003000B004E004A00120050>Tj
/TT1 1 Tf
3.498 0 0 3.498 598.72 391.1395 Tm
(2)Tj
6 0 0 6 600.6654 389.1415 Tm
(\), mean \261 SD)Tj
20.683 0 Td
(26 \261 3)Tj
9.49 0 Td
(25 \261 3)Tj
4.75 0 0 4.75 568.5514 377.9077 Tm
(SD, standard deviation. )Tj
ET
0.6 0 0.06 0 k
/GS0 gs
1103.959 575.695 51.024 -8.752 re
1154.983 575.695 82.205 -8.752 re
1237.188 575.695 41.658 -38.504 re
1278.845 575.695 41.658 -38.504 re
1320.503 575.695 33.402 -38.504 re
1103.959 566.943 51.024 -29.752 re
1154.983 566.943 45.354 -29.752 re
1200.337 566.943 36.85 -29.752 re
f
0 0 0 0 k
1103.959 537.191 51.024 -15.752 re
1154.983 537.191 45.354 -15.752 re
1200.337 537.191 36.85 -15.752 re
1237.188 537.191 41.658 -15.752 re
1278.845 537.191 41.658 -15.752 re
1320.503 537.191 33.402 -15.752 re
1103.959 521.439 51.024 -15.752 re
1154.983 521.439 45.354 -15.752 re
1200.337 521.439 36.85 -15.752 re
1237.188 521.439 41.658 -15.752 re
1278.845 521.439 41.658 -15.752 re
1320.503 521.439 33.402 -15.752 re
1103.959 474.183 51.024 -15.752 re
1154.983 474.183 45.354 -15.752 re
1200.337 474.183 36.85 -15.752 re
1237.188 474.183 41.658 -15.752 re
1278.845 474.183 41.658 -15.752 re
1320.503 474.183 33.402 -15.752 re
1103.959 458.431 51.024 -15.752 re
1154.983 458.431 45.354 -15.752 re
1200.337 458.431 36.85 -15.752 re
1237.188 458.431 41.658 -15.752 re
1278.845 458.431 41.658 -15.752 re
1320.503 458.431 33.402 -15.752 re
1103.959 442.679 249.946 -18.314 re
f
0.6 0 0.06 0 k
1103.959 505.687 51.024 -31.504 re
1154.983 505.687 82.205 -8.752 re
1237.188 505.687 41.658 -31.504 re
1278.845 505.687 41.658 -31.504 re
1320.503 505.687 33.402 -31.504 re
1154.983 496.935 45.354 -22.752 re
1200.337 496.935 36.85 -22.752 re
f
0.593 w
/GS2 gs
q 1 0 0 1 1103.5842 575.6945 cm
0 0 m
51.399 0 l
S
Q
q 1 0 0 1 1154.9829 575.6945 cm
0 0 m
45.354 0 l
S
Q
q 1 0 0 1 1200.3372 575.6945 cm
0 0 m
36.85 0 l
S
Q
q 1 0 0 1 1237.1876 575.6945 cm
0 0 m
41.658 0 l
S
Q
q 1 0 0 1 1278.8452 575.6945 cm
0 0 m
41.658 0 l
S
Q
q 1 0 0 1 1320.5029 575.6945 cm
0 0 m
33.777 0 l
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0.75 w
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q 1 0 0 1 1353.9053 566.9425 cm
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0 0 m
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q 1 0 0 1 1353.9053 537.1906 cm
0 0 m
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0 0 0 0 K
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q 1 0 0 1 1237.1876 566.9425 cm
0 0 m
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Q
q 1 0 0 1 1278.8452 566.9425 cm
0 0 m
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Q
q 1 0 0 1 1320.5029 566.9425 cm
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q 1 0 0 1 1154.9829 537.1906 cm
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q 1 0 0 1 1237.1876 537.1906 cm
0 0 m
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Q
q 1 0 0 1 1278.8452 537.1906 cm
0 0 m
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S
Q
q 1 0 0 1 1320.5029 537.1906 cm
0 0 m
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0.6 0 0.06 0 K
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q 1 0 0 1 1200.3372 521.6886 cm
0 0 m
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q 1 0 0 1 1237.1876 521.6886 cm
0 0 m
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Q
q 1 0 0 1 1278.8452 521.6886 cm
0 0 m
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S
Q
q 1 0 0 1 1320.5029 521.6886 cm
0 0 m
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q 1 0 0 1 1154.9829 505.6866 cm
0 0 m
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Q
q 1 0 0 1 1200.3372 505.6866 cm
0 0 m
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Q
q 1 0 0 1 1237.1876 505.6866 cm
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Q
q 1 0 0 1 1278.8452 505.6866 cm
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q 1 0 0 1 1320.5029 505.6866 cm
0 0 m
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Q
q 1 0 0 1 1353.9053 505.6866 cm
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S
Q
q 1 0 0 1 1103.9592 496.9347 cm
0 0 m
0 8.752 l
S
Q
q 1 0 0 1 1353.9053 496.9347 cm
0 0 m
0 8.752 l
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Q
q 1 0 0 1 1103.9592 474.1827 cm
0 0 m
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Q
q 1 0 0 1 1353.9053 474.1827 cm
0 0 m
0 22.752 l
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Q
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0 0 m
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0 0 m
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Q
q 1 0 0 1 1200.3372 458.6807 cm
0 0 m
0 15.502 l
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q 1 0 0 1 1237.1876 458.6807 cm
0 0 m
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q 1 0 0 1 1278.8452 458.6807 cm
0 0 m
0 15.502 l
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q 1 0 0 1 1320.5029 458.6807 cm
0 0 m
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q 1 0 0 1 1353.9053 458.4307 cm
0 0 m
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Q
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q 1 0 0 1 1200.3372 443.0538 cm
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Q
q 1 0 0 1 1237.1876 443.0538 cm
0 0 m
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S
Q
q 1 0 0 1 1278.8452 443.0538 cm
0 0 m
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S
Q
q 1 0 0 1 1320.5029 443.0538 cm
0 0 m
0 15.127 l
S
Q
q 1 0 0 1 1353.9053 443.0538 cm
0 0 m
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0.3 0 0.03 0 K
0.5 w
q 1 0 0 1 1104.3342 521.4386 cm
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S
Q
q 1 0 0 1 1154.9829 521.4386 cm
0 0 m
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S
Q
q 1 0 0 1 1200.3372 521.4386 cm
0 0 m
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Q
q 1 0 0 1 1237.1876 521.4386 cm
0 0 m
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S
Q
q 1 0 0 1 1278.8452 521.4386 cm
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S
Q
q 1 0 0 1 1320.5029 521.4386 cm
0 0 m
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Q
q 1 0 0 1 1104.3342 458.4307 cm
0 0 m
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S
Q
q 1 0 0 1 1154.9829 458.4307 cm
0 0 m
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Q
q 1 0 0 1 1200.3372 458.4307 cm
0 0 m
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Q
q 1 0 0 1 1237.1876 458.4307 cm
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S
Q
q 1 0 0 1 1278.8452 458.4307 cm
0 0 m
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S
Q
q 1 0 0 1 1320.5029 458.4307 cm
0 0 m
33.027 0 l
S
Q
0 0 0 0 K
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0 0 m
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S
Q
q 1 0 0 1 1200.3372 566.9425 cm
0 0 m
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S
Q
q 1 0 0 1 1155.3579 496.9347 cm
0 0 m
44.979 0 l
S
Q
q 1 0 0 1 1200.3372 496.9347 cm
0 0 m
36.475 0 l
S
Q
0.75 w
q 1 0 0 1 1200.3372 474.1827 cm
0 0 m
0 22.502 l
S
Q
q 1 0 0 1 1237.1876 474.1827 cm
0 0 m
0 22.752 l
S
Q
q 1 0 0 1 1237.1876 496.9347 cm
0 0 m
0 8.752 l
S
Q
q 1 0 0 1 1278.8452 496.9347 cm
0 0 m
0 8.752 l
S
Q
q 1 0 0 1 1320.5029 496.9347 cm
0 0 m
0 8.752 l
S
Q
q 1 0 0 1 1278.8452 474.1827 cm
0 0 m
0 22.752 l
S
Q
q 1 0 0 1 1320.5029 474.1827 cm
0 0 m
0 22.752 l
S
Q
q 1 0 0 1 1154.9829 496.9347 cm
0 0 m
0 8.752 l
S
Q
q 1 0 0 1 1154.9829 474.1827 cm
0 0 m
0 22.752 l
S
Q
0.6 0 0.06 0 K
q 1 0 0 1 1103.5842 442.6788 cm
0 0 m
51.399 0 l
S
Q
q 1 0 0 1 1154.9829 442.6788 cm
0 0 m
45.354 0 l
S
Q
q 1 0 0 1 1200.3372 442.6788 cm
0 0 m
36.85 0 l
S
Q
q 1 0 0 1 1237.1876 442.6788 cm
0 0 m
41.658 0 l
S
Q
q 1 0 0 1 1278.8452 442.6788 cm
0 0 m
41.658 0 l
S
Q
q 1 0 0 1 1320.5029 442.6788 cm
0 0 m
33.777 0 l
S
Q
BT
1 0.8 0.38 0.29 k
/GS0 gs
/TT0 1 Tf
6 0 0 6 1103.9592 593.9465 Tm
[(T)73.9 (able 3. Comparisons of Baseline-Corrected Plasma Epinephrine PK Paramete\
rs )]TJ
0 -1.167 Td
[(After 2 Epinephrine 6.6 mg IN \(Opposite or Same Nostrils\) )38.1 (Administrations V)55 (ersus 1 )]TJ
0 -1.167 Td
[(Epinephrine 0.3 mg IM )38 (Administration)]TJ
12.964 -1.695 Td
[(T)54.8 (reatment)]TJ
10.239 -3.792 Td
(Geometric )Tj
-0.055 -1.167 Td
(mean ratio)Tj
8.471 2.333 Td
(90% )Tj
( )Tj
/C2_2 1 Tf
-0.02 Tc 0.02 Tw -1.559 -1.167 Td
[<00460052005100C000470048005100460048>-20.2 <0003>]TJ
/TT0 1 Tf
0 Tc 0 Tw 0.503 -1.167 Td
(intervals)Tj
7.062 2.333 Td
(Intra-)Tj
( )Tj
-0.5 -1.167 Td
(subject )Tj
( )Tj
0.611 -1.167 Td
(CV%)Tj
-25.813 3.5 Td
(D)Tj
-2.057 -1.167 Td
(2 x 6.6 mg )Tj
-0.443 -1.167 Td
(IN, opposite )Tj
1.055 -1.167 Td
(nostrils)Tj
8.295 3.5 Td
(B)Tj
-1.917 -1.167 Td
(0.3 mg IM )Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
-16.383 -3.792 Td
(C)Tj
3.498 0 0 3.498 1111.127 530.0732 Tm
(max)Tj
/C2_1 1 Tf
6 0 0 6 1106.7939 524.2733 Tm
<002A002F00360030000F00030053004A00120050002F>Tj
/TT1 1 Tf
10.407 1.167 Td
(n = 38)Tj
0.57 -1.167 Td
(412)Tj
6.039 1.167 Td
[(n = 1)73.8 (10)]TJ
0.811 -1.167 Td
(284)Tj
6.542 0.583 Td
(145)Tj
5.868 0 Td
[(1)73.6 (14\226185)]TJ
7.609 0 Td
(71)Tj
-37.846 -2.042 Td
(AUC)Tj
3.498 0 0 3.498 1119.4619 514.3213 Tm
(0\226360)Tj
6 0 0 6 1129.189 515.5213 Tm
( GLSM, )Tj
/C2_1 1 Tf
-0.01 Tc 0.01 Tw -3.733 -1.167 Td
<0050004C0051000D0053004A00120050002F>Tj
/TT1 1 Tf
0 Tc 0 Tw 10.407 1.167 Td
(n = 36)Tj
-0.125 -1.167 Td
(37,380)Tj
6.698 1.167 Td
(n = 102)Tj
0.153 -1.167 Td
(16,850)Tj
7.237 0.583 Td
(222)Tj
5.831 0 Td
(184\226267)Tj
7.645 0 Td
(27)Tj
1 0.8 0.38 0.29 k
/GS0 gs
/TT0 1 Tf
-25.354 -2.042 Td
[(T)54.8 (reatment)]TJ
10.239 -2.625 Td
(Geometric )Tj
-0.055 -1.167 Td
(mean ratio)Tj
8.471 2.333 Td
(90% )Tj
( )Tj
/C2_2 1 Tf
-0.02 Tc 0.02 Tw -1.559 -1.167 Td
[<00460052005100C000470048005100460048>-20.2 <0003>]TJ
/TT0 1 Tf
0 Tc 0 Tw 0.503 -1.167 Td
(intervals)Tj
7.062 2.333 Td
(Intra-)Tj
( )Tj
-0.5 -1.167 Td
(subject )Tj
( )Tj
0.611 -1.167 Td
(CV%)Tj
-25.785 2.333 Td
(E)Tj
-2.862 -1.167 Td
(2 x 6.6 mg IN, )Tj
0.25 -1.167 Td
(same nostril)Tj
9.435 2.333 Td
(B)Tj
-1.917 -1.167 Td
(0.3 mg IM)Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
-16.383 -2.625 Td
(C)Tj
3.498 0 0 3.498 1111.127 467.0654 Tm
(max)Tj
/C2_1 1 Tf
6 0 0 6 1106.7939 461.2654 Tm
<002A002F00360030000F00030053004A00120050002F>Tj
/TT1 1 Tf
10.407 1.167 Td
(n = 40)Tj
0.57 -1.167 Td
(752 )Tj
6.039 1.167 Td
[(n = 1)73.8 (10)]TJ
0.811 -1.167 Td
(284)Tj
6.542 0.583 Td
(265)Tj
5.831 0 Td
(209\226337)Tj
7.645 0 Td
(71)Tj
-37.846 -2.042 Td
(AUC)Tj
3.498 0 0 3.498 1119.4619 451.3134 Tm
(0\226360)Tj
6 0 0 6 1129.189 452.5134 Tm
( GLSM, )Tj
/C2_1 1 Tf
-0.01 Tc 0.01 Tw -3.733 -1.167 Td
<0050004C0051000D0053004A00120050002F>Tj
/TT1 1 Tf
0 Tc 0 Tw 10.407 1.167 Td
(n = 38)Tj
-0.125 -1.167 Td
(54,300 )Tj
6.698 1.167 Td
(n = 102)Tj
0.153 -1.167 Td
(16,860 )Tj
7.237 0.583 Td
(322)Tj
5.831 0 Td
(274\226379)Tj
7.645 0 Td
(27)Tj
4.75 0 0 4.75 1103.9592 434.8643 Tm
(AUC)Tj
2.7692 0 0 2.7692 1113.988 433.9143 Tm
(0\226360)Tj
4.75 0 0 4.75 1121.6886 434.8643 Tm
(, area under the plasma concentration-time curve from time 0 to the 360-\
minute postdose time point; )Tj
44.634 0 Td
( )Tj
-48.366 -1.105 Td
(C)Tj
2.7692 0 0 2.7692 1107.3895 428.6643 Tm
(max)Tj
/C2_1 1 Tf
4.75 0 0 4.75 1112.6211 429.6143 Tm
[<000F000300500044005B004C00500058005000030052004500560048005500590048004700030046005200510046004800510057005500440057004C00520051001E000300260039>90.5 <000F0003004600520048004900C00046004C0048005100570003005200490003005900440055004C00440057004C00520051001E0003002A002F00360030000F0003004A004800520050004800570055004C00460003004F00480044005600570003005600540058004400550048005600030050004800440051001E0003002C0030000F0003>]TJ
/TT1 1 Tf
-1.824 -1.105 Td
(intramuscular; IN, intranasal; PK, pharmacokinetic.)Tj
ET
0.6 0 0.06 0 k
/GS0 gs
836.255 760.571 65.197 -11.339 re
901.452 760.571 316.717 -11.339 re
1218.169 760.571 135.736 -11.339 re
836.255 749.232 65.197 -38.169 re
901.452 749.232 45.245 -38.169 re
946.697 749.232 45.245 -38.169 re
991.943 749.232 45.245 -38.169 re
1037.188 749.232 45.245 -38.169 re
1082.433 749.232 45.245 -38.169 re
1127.679 749.232 45.245 -38.169 re
1172.924 749.232 45.245 -38.169 re
1218.169 749.232 45.245 -38.169 re
1263.415 749.232 45.245 -38.169 re
1308.66 749.232 45.245 -38.169 re
f
0 0 0 0 k
836.255 711.063 65.197 -18.425 re
901.452 711.063 45.245 -18.425 re
946.697 711.063 45.245 -18.425 re
991.943 711.063 45.245 -18.425 re
1037.188 711.063 45.245 -18.425 re
1082.433 711.063 45.245 -18.425 re
1127.679 711.063 45.245 -18.425 re
1172.924 711.063 45.245 -18.425 re
1218.169 711.063 45.245 -18.425 re
1263.415 711.063 45.245 -18.425 re
1308.66 711.063 45.245 -18.425 re
836.255 692.638 65.197 -22.752 re
901.452 692.638 45.245 -22.752 re
946.697 692.638 45.245 -22.752 re
991.943 692.638 45.245 -22.752 re
1037.188 692.638 45.245 -22.752 re
1082.433 692.638 45.245 -22.752 re
1127.679 692.638 45.245 -22.752 re
1172.924 692.638 45.245 -22.752 re
1218.169 692.638 45.245 -22.752 re
1263.415 692.638 45.245 -22.752 re
1308.66 692.638 45.245 -22.752 re
836.255 669.886 65.197 -18.425 re
901.452 669.886 45.245 -18.425 re
946.697 669.886 45.245 -18.425 re
991.943 669.886 45.245 -18.425 re
1037.188 669.886 45.245 -18.425 re
1082.433 669.886 45.245 -18.425 re
1127.679 669.886 45.245 -18.425 re
1172.924 669.886 45.245 -18.425 re
1218.169 669.886 45.245 -18.425 re
1263.415 669.886 45.245 -18.425 re
1308.66 669.886 45.245 -18.425 re
836.255 651.461 65.197 -18.425 re
901.452 651.461 45.245 -18.425 re
946.697 651.461 45.245 -18.425 re
991.943 651.461 45.245 -18.425 re
1037.188 651.461 45.245 -18.425 re
1082.433 651.461 45.245 -18.425 re
1127.679 651.461 45.245 -18.425 re
1172.924 651.461 45.245 -18.425 re
1218.169 651.461 45.245 -18.425 re
1263.415 651.461 45.245 -18.425 re
1308.66 651.461 45.245 -18.425 re
836.255 633.035 517.65 -19.314 re
f
0.593 w
/GS2 gs
q 1 0 0 1 835.959 760.5709 cm
0 0 m
65.493 0 l
S
Q
q 1 0 0 1 901.4521 760.5709 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 946.6974 760.5709 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 991.9428 760.5709 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1037.1881 760.5709 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1082.4335 760.5709 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1127.6787 760.5709 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1172.9241 760.5709 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1218.1694 760.5709 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1263.4147 760.5709 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1308.66 760.5709 cm
0 0 m
45.542 0 l
S
Q
q 1 0 0 1 835.959 749.2322 cm
0 0 m
65.118 0 l
S
Q
q 1 0 0 1 836.2553 749.5286 cm
0 0 m
0 10.746 l
S
Q
0 0 0 0 K
q 1 0 0 1 1218.1694 749.4822 cm
0 0 m
0 10.792 l
S
Q
0.6 0 0.06 0 K
q 1 0 0 1 1353.9053 749.4822 cm
0 0 m
0 10.792 l
S
Q
0.75 w
q 1 0 0 1 836.2553 711.063 cm
0 0 m
0 37.873 l
S
Q
q 1 0 0 1 1353.9053 711.063 cm
0 0 m
0 37.919 l
S
Q
0 0 0 0 K
q 1 0 0 1 946.6974 711.063 cm
0 0 m
0 37.919 l
S
Q
q 1 0 0 1 991.9428 711.063 cm
0 0 m
0 37.919 l
S
Q
q 1 0 0 1 1037.1881 711.063 cm
0 0 m
0 37.919 l
S
Q
q 1 0 0 1 1082.4335 711.063 cm
0 0 m
0 37.919 l
S
Q
q 1 0 0 1 1127.6787 711.063 cm
0 0 m
0 37.919 l
S
Q
q 1 0 0 1 1172.9241 711.063 cm
0 0 m
0 37.919 l
S
Q
q 1 0 0 1 1218.1694 711.063 cm
0 0 m
0 37.919 l
S
Q
q 1 0 0 1 1263.4147 711.063 cm
0 0 m
0 37.919 l
S
Q
q 1 0 0 1 1308.66 711.063 cm
0 0 m
0 37.919 l
S
Q
0.6 0 0.06 0 K
q 1 0 0 1 836.2553 692.6378 cm
0 0 m
0 18.425 l
S
Q
q 1 0 0 1 901.4521 692.8878 cm
0 0 m
0 18.175 l
S
Q
q 1 0 0 1 946.6974 692.8878 cm
0 0 m
0 18.175 l
S
Q
q 1 0 0 1 991.9428 692.8878 cm
0 0 m
0 18.175 l
S
Q
q 1 0 0 1 1037.1881 692.8878 cm
0 0 m
0 18.175 l
S
Q
q 1 0 0 1 1082.4335 692.8878 cm
0 0 m
0 18.175 l
S
Q
q 1 0 0 1 1127.6787 692.8878 cm
0 0 m
0 18.175 l
S
Q
q 1 0 0 1 1172.9241 692.8878 cm
0 0 m
0 18.175 l
S
Q
q 1 0 0 1 1218.1694 692.8878 cm
0 0 m
0 18.175 l
S
Q
q 1 0 0 1 1263.4147 692.8878 cm
0 0 m
0 18.175 l
S
Q
q 1 0 0 1 1308.66 692.8878 cm
0 0 m
0 18.175 l
S
Q
q 1 0 0 1 1353.9053 692.6378 cm
0 0 m
0 18.425 l
S
Q
q 1 0 0 1 836.2553 669.8858 cm
0 0 m
0 22.752 l
S
Q
q 1 0 0 1 901.4521 670.1358 cm
0 0 m
0 22.252 l
S
Q
q 1 0 0 1 946.6974 670.1358 cm
0 0 m
0 22.252 l
S
Q
q 1 0 0 1 991.9428 670.1358 cm
0 0 m
0 22.252 l
S
Q
q 1 0 0 1 1037.1881 670.1358 cm
0 0 m
0 22.252 l
S
Q
q 1 0 0 1 1082.4335 670.1358 cm
0 0 m
0 22.252 l
S
Q
q 1 0 0 1 1127.6787 670.1358 cm
0 0 m
0 22.252 l
S
Q
q 1 0 0 1 1172.9241 670.1358 cm
0 0 m
0 22.252 l
S
Q
q 1 0 0 1 1218.1694 670.1358 cm
0 0 m
0 22.252 l
S
Q
q 1 0 0 1 1263.4147 670.1358 cm
0 0 m
0 22.252 l
S
Q
q 1 0 0 1 1308.66 670.1358 cm
0 0 m
0 22.252 l
S
Q
q 1 0 0 1 1353.9053 669.8858 cm
0 0 m
0 22.752 l
S
Q
q 1 0 0 1 836.2553 651.4606 cm
0 0 m
0 18.425 l
S
Q
q 1 0 0 1 901.4521 651.7106 cm
0 0 m
0 17.925 l
S
Q
q 1 0 0 1 946.6974 651.7106 cm
0 0 m
0 17.925 l
S
Q
q 1 0 0 1 991.9428 651.7106 cm
0 0 m
0 17.925 l
S
Q
q 1 0 0 1 1037.1881 651.7106 cm
0 0 m
0 17.925 l
S
Q
q 1 0 0 1 1082.4335 651.7106 cm
0 0 m
0 17.925 l
S
Q
q 1 0 0 1 1127.6787 651.7106 cm
0 0 m
0 17.925 l
S
Q
q 1 0 0 1 1172.9241 651.7106 cm
0 0 m
0 17.925 l
S
Q
q 1 0 0 1 1218.1694 651.7106 cm
0 0 m
0 17.925 l
S
Q
q 1 0 0 1 1263.4147 651.7106 cm
0 0 m
0 17.925 l
S
Q
q 1 0 0 1 1308.66 651.7106 cm
0 0 m
0 17.925 l
S
Q
q 1 0 0 1 1353.9053 651.4606 cm
0 0 m
0 18.425 l
S
Q
q 1 0 0 1 836.2553 633.4104 cm
0 0 m
0 18.05 l
S
Q
q 1 0 0 1 901.4521 633.4104 cm
0 0 m
0 17.8 l
S
Q
q 1 0 0 1 946.6974 633.4104 cm
0 0 m
0 17.8 l
S
Q
q 1 0 0 1 991.9428 633.4104 cm
0 0 m
0 17.8 l
S
Q
q 1 0 0 1 1037.1881 633.4104 cm
0 0 m
0 17.8 l
S
Q
q 1 0 0 1 1082.4335 633.4104 cm
0 0 m
0 17.8 l
S
Q
q 1 0 0 1 1127.6787 633.4104 cm
0 0 m
0 17.8 l
S
Q
q 1 0 0 1 1172.9241 633.4104 cm
0 0 m
0 17.8 l
S
Q
q 1 0 0 1 1218.1694 633.4104 cm
0 0 m
0 17.8 l
S
Q
q 1 0 0 1 1263.4147 633.4104 cm
0 0 m
0 17.8 l
S
Q
q 1 0 0 1 1308.66 633.4104 cm
0 0 m
0 17.8 l
S
Q
q 1 0 0 1 1353.9053 633.4104 cm
0 0 m
0 18.05 l
S
Q
0 0 0 0 K
0.5 w
q 1 0 0 1 901.8271 749.2322 cm
0 0 m
44.87 0 l
S
Q
q 1 0 0 1 946.6974 749.2322 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 991.9428 749.2322 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1037.1881 749.2322 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1082.4335 749.2322 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1127.6787 749.2322 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1172.9241 749.2322 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1218.1694 749.2322 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1263.4147 749.2322 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1308.66 749.2322 cm
0 0 m
45.62 0 l
S
Q
0.3 0 0.03 0 K
q 1 0 0 1 836.6303 692.6378 cm
0 0 m
64.822 0 l
S
Q
q 1 0 0 1 901.4521 692.6378 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 946.6974 692.6378 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 991.9428 692.6378 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1037.1881 692.6378 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1082.4335 692.6378 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1127.6787 692.6378 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1172.9241 692.6378 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1218.1694 692.6378 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1263.4147 692.6378 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1308.66 692.6378 cm
0 0 m
44.87 0 l
S
Q
q 1 0 0 1 836.6303 669.8858 cm
0 0 m
64.822 0 l
S
Q
q 1 0 0 1 901.4521 669.8858 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 946.6974 669.8858 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 991.9428 669.8858 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1037.1881 669.8858 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1082.4335 669.8858 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1127.6787 669.8858 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1172.9241 669.8858 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1218.1694 669.8858 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1263.4147 669.8858 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1308.66 669.8858 cm
0 0 m
44.87 0 l
S
Q
q 1 0 0 1 836.6303 651.4606 cm
0 0 m
64.822 0 l
S
Q
q 1 0 0 1 901.4521 651.4606 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 946.6974 651.4606 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 991.9428 651.4606 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1037.1881 651.4606 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1082.4335 651.4606 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1127.6787 651.4606 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1172.9241 651.4606 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1218.1694 651.4606 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1263.4147 651.4606 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1308.66 651.4606 cm
0 0 m
44.87 0 l
S
Q
0 0 0 0 K
0.75 w
q 1 0 0 1 901.4521 749.2322 cm
0 0 m
0 11.042 l
S
Q
q 1 0 0 1 901.4521 711.063 cm
0 0 m
0 38.169 l
S
Q
0.6 0 0.06 0 K
q 1 0 0 1 835.8803 633.0354 cm
0 0 m
65.572 0 l
S
Q
q 1 0 0 1 901.4521 633.0354 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 946.6974 633.0354 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 991.9428 633.0354 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1037.1881 633.0354 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1082.4335 633.0354 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1127.6787 633.0354 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1172.9241 633.0354 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1218.1694 633.0354 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1263.4147 633.0354 cm
0 0 m
45.245 0 l
S
Q
q 1 0 0 1 1308.66 633.0354 cm
0 0 m
45.62 0 l
S
Q
BT
1 0.8 0.38 0.29 k
/GS0 gs
/TT0 1 Tf
6 0 0 6 836.2552 764.8228 Tm
[(T)73.9 (able 2. Baseline-Corrected Plasma Epinephrine PK after Epinephrine IN or\
IM)]TJ
35.87 -1.91 Td
(Part 1)Tj
37.704 0 Td
(Part 2)Tj
-73.102 -6.577 Td
(PK parameter)Tj
13.821 4.667 Td
(A)Tj
-1.88 -1.167 Td
(6.6 mg IN)Tj
0.791 -1.167 Td
(n = 55)Tj
8.333 2.333 Td
(B1)Tj
-1.778 -1.167 Td
(0.3 mg IM, )Tj
5.112 0 Td
( )Tj
/C2_2 1 Tf
-3.64 -1.167 Td
<00C00055005600570003>Tj
/TT0 1 Tf
( )Tj
-0.02 Tc 0.02 Tw -2.37 -1.167 Td
(administration)Tj
0 Tc 0 Tw 1.883 -1.167 Td
(n = 55)Tj
8.333 4.667 Td
(B2)Tj
-1.778 -1.167 Td
(0.3 mg IM, )Tj
0.667 -1.167 Td
(second )Tj
( )Tj
-0.02 Tc 0.02 Tw -1.564 -1.167 Td
(administration)Tj
0 Tc 0 Tw 1.883 -1.167 Td
(n = 55)Tj
8.472 4.667 Td
(B, )Tj
( )Tj
-1.139 -1.167 Td
(pooled)Tj
-0.043 -1.167 Td
[(n = 1)55.1 (10)]TJ
8.584 2.333 Td
(C1)Tj
-1.778 -1.167 Td
(0.5 mg IM, )Tj
5.112 0 Td
( )Tj
/C2_2 1 Tf
-3.64 -1.167 Td
<00C00055005600570003>Tj
/TT0 1 Tf
( )Tj
-0.02 Tc 0.02 Tw -2.37 -1.167 Td
(administration)Tj
0 Tc 0 Tw 1.883 -1.167 Td
(n = 55)Tj
8.333 4.667 Td
(C2)Tj
-1.778 -1.167 Td
(0.5 mg IM, )Tj
0.667 -1.167 Td
(second )Tj
( )Tj
-0.02 Tc 0.02 Tw -1.564 -1.167 Td
(administration)Tj
0 Tc 0 Tw 1.883 -1.167 Td
(n = 55)Tj
6.695 4.667 Td
(C, pooled)Tj
0.595 -1.167 Td
[(n = 1)55.1 (10)]TJ
8.862 1.167 Td
(D)Tj
-2.835 -1.167 Td
(2 x 6.6 mg IN, )Tj
6.648 0 Td
( )Tj
-5.535 -1.167 Td
(opposite )Tj
0.277 -1.167 Td
(nostrils)Tj
0.375 -1.167 Td
(n = 38)Tj
8.639 4.667 Td
(E)Tj
-2.862 -1.167 Td
(2 x 6.6 mg IN, )Tj
1.917 -1.167 Td
(same )Tj
( )Tj
-0.249 -1.167 Td
(nostril)Tj
0.096 -1.167 Td
(n = 40)Tj
8.667 4.667 Td
(F)Tj
-2.946 -1.167 Td
(2 x 0.3 mg IM, )Tj
6.731 0 Td
( )Tj
-5.563 -1.167 Td
(opposite)Tj
4.166 0 Td
( )Tj
-3.583 -1.167 Td
(thighs)Tj
0.068 -1.167 Td
(n = 39)Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
-80.601 -1.681 Td
(C)Tj
3.498 0 0 3.498 843.4229 702.609 Tm
(max)Tj
/C2_1 1 Tf
6 0 0 6 850.0311 703.809 Tm
<0003000B0053004A00120050002F000C000F000300500048004400510003>Tj
/TT1 1 Tf
-1.824 -1.167 Td
(\261 SD)Tj
11.943 0.583 Td
(193 \261 139)Tj
7.541 0 Td
(308 \261 152)Tj
7.541 0 Td
(440 \261 692)Tj
7.541 0 Td
(374 \261 503)Tj
7.263 0 Td
(712 \261 2468)Tj
7.819 0 Td
(351 \261 206)Tj
7.263 0 Td
(532 \261 1753)Tj
7.819 0 Td
(644 \261 853)Tj
6.985 0 Td
(1237 \261 2099)Tj
8.097 0 Td
(758 \261 626)Tj
-79.811 -2.265 Td
(T)Tj
3.498 0 0 3.498 842.7549 685.5204 Tm
(max)Tj
6 0 0 6 849.3632 686.7205 Tm
( \(min\), )Tj
( )Tj
-0.03 Tc -1.712 -1.167 Td
[(median \(minimum,)-29.8 ( )]TJ
0 Tc 7.992 0 Td
( )Tj
-7.992 -1.167 Td
(maximum\))Tj
11.746 1.167 Td
(25 \(2, 122\))Tj
7.819 0 Td
(16 \(2, 60\))Tj
7.541 0 Td
(10 \(1, 61\))Tj
7.541 0 Td
(15 \(1, 61\))Tj
7.541 0 Td
(46 \(3, 91\))Tj
7.263 0 Td
(45 \(5, 120\))Tj
7.541 0 Td
(46 \(3, 120\))Tj
7.819 0 Td
(25 \(3, 61\))Tj
7.541 0 Td
(16 \(3, 91\))Tj
7.541 0 Td
(15 \(3, 45\))Tj
-79.892 -2.848 Td
(AUC)Tj
3.498 0 0 3.498 851.7578 661.4319 Tm
(0\22620)Tj
/C2_1 1 Tf
6 0 0 6 859.5395 662.6319 Tm
<0003000B0050004C0051000D0053004A00120050002F000C000F0003>Tj
/TT1 1 Tf
-3.408 -1.167 Td
(mean \261 SD)Tj
11.387 0.583 Td
(1804 \261 1369)Tj
7.541 0 Td
(2898 \261 1808)Tj
7.541 0 Td
(3628 \261 3229)Tj
7.541 0 Td
(3263 \261 2631)Tj
7.578 0 Td
[(3832 \261 91)73.3 (14)]TJ
7.504 0 Td
(1777 \261 1544)Tj
7.541 0 Td
(2804 \261 6587)Tj
7.541 0 Td
(6367 \261 9666)Tj
6.707 0 Td
(13,380 \261 21,134)Tj
8.375 0 Td
(7993 \261 7771)Tj
-79.255 -2.488 Td
(AUC)Tj
3.498 0 0 3.498 851.7578 643.0067 Tm
(0\226360)Tj
/C2_1 1 Tf
6 0 0 6 861.4849 644.2067 Tm
<0003000B0050004C0051000D0053004A00120050002F000C000F0003>Tj
/TT1 1 Tf
-3.733 -1.167 Td
(mean \261 SD)Tj
-0.03 Tc 10.616 0.583 Td
(18,970 \261 21,708)Tj
0 Tc 3.498 0 0 3.498 943.4171 642.7047 Tm
(a)Tj
6 0 0 6 949.1843 640.7067 Tm
(17,980 \261 5698)Tj
3.498 0 0 3.498 987.5104 642.7047 Tm
(b)Tj
6 0 0 6 994.5278 640.7067 Tm
(18,470 \261 7761)Tj
3.498 0 0 3.498 1032.854 642.7047 Tm
(c)Tj
6 0 0 6 1040.6476 640.7067 Tm
(18,230 \261 6799)Tj
-0.02 Tc 7.264 0 Td
(35,170 \261 12,887)Tj
0 Tc 7.818 0 Td
(30,880 \261 9467)Tj
7.161 0 Td
[(33,020 \261 1)73.5 (1,460)]TJ
-0.04 Tc 7.642 0 Td
(47,940 \261 38,481)Tj
0 Tc 3.498 0 0 3.498 1259.6843 642.7047 Tm
(d)Tj
-0.04 Tc 6 0 0 6 1265.1995 640.7067 Tm
(64,380 \261 40,957)Tj
0 Tc 3.498 0 0 3.498 1304.9296 642.7047 Tm
(e)Tj
-0.02 Tc 6 0 0 6 1310.4575 640.7067 Tm
(39,080 \261 18,710)Tj
0 Tc 2.7692 0 0 2.7692 836.2552 626.8027 Tm
(a)Tj
4.75 0 0 4.75 837.7953 625.2209 Tm
(n=49; )Tj
2.7692 0 0 2.7692 851.1339 626.8027 Tm
(b)Tj
4.75 0 0 4.75 852.674 625.2209 Tm
(n=50; )Tj
2.7692 0 0 2.7692 866.0125 626.8027 Tm
(c)Tj
4.75 0 0 4.75 867.3971 625.2209 Tm
(n=52; )Tj
2.7692 0 0 2.7692 880.7356 626.8027 Tm
(d)Tj
4.75 0 0 4.75 882.2758 625.2209 Tm
(n=36; )Tj
2.7692 0 0 2.7692 895.6143 626.8027 Tm
(e)Tj
4.75 0 0 4.75 897.1544 625.2209 Tm
(n=38.)Tj
-12.821 -1.316 Td
(AUC)Tj
2.7692 0 0 2.7692 846.2841 618.0209 Tm
(0\22620)Tj
4.75 0 0 4.75 852.4445 618.9709 Tm
[(, area under the plasma concentration-time curve from time 0 to the 20-m\
inute postdose time point; )52.1 (AUC)]TJ
2.7692 0 0 2.7692 1071.5823 618.0209 Tm
(0\226360)Tj
4.75 0 0 4.75 1079.2828 618.9709 Tm
[(, )55 (AUC from time 0 to the 360-minute postdose time point; C)]TJ
2.7692 0 0 2.7692 1203.634 618.0209 Tm
(max)Tj
4.75 0 0 4.75 1208.8656 618.9709 Tm
(, maximum observed concentration; IM, intramuscular; IN, intranasal; )Tj
-78.444 -1.105 Td
[(SD, standard deviation; )16.7 (T)]TJ
2.7692 0 0 2.7692 889.7692 612.7709 Tm
(max)Tj
4.75 0 0 4.75 895.0008 613.7209 Tm
(, time to reach maximum concentration.)Tj
ET
0.6 0 0.06 0 k
/GS0 gs
836.255 246.227 68.031 -8.752 re
904.287 246.227 281.012 -8.752 re
1185.298 246.227 168.607 -8.752 re
836.255 237.475 68.031 -29.752 re
904.287 237.475 56.202 -29.752 re
960.489 237.475 56.202 -29.752 re
1016.691 237.475 56.202 -29.752 re
1072.894 237.475 56.202 -29.752 re
1129.096 237.475 56.202 -29.752 re
1185.298 237.475 56.202 -29.752 re
1241.501 237.475 56.202 -29.752 re
1297.703 237.475 56.202 -29.752 re
f
0 0 0 0 k
836.255 207.723 68.031 -9.625 re
904.287 207.723 56.202 -9.625 re
960.489 207.723 56.202 -9.625 re
1016.691 207.723 56.202 -9.625 re
1072.894 207.723 56.202 -9.625 re
1129.096 207.723 56.202 -9.625 re
1185.298 207.723 56.202 -9.625 re
1241.501 207.723 56.202 -9.625 re
1297.703 207.723 56.202 -9.625 re
836.255 198.098 68.031 -9.921 re
904.287 198.098 56.202 -9.921 re
960.489 198.098 56.202 -9.921 re
1016.691 198.098 56.202 -9.921 re
1072.894 198.098 56.202 -9.921 re
1129.096 198.098 56.202 -9.921 re
1185.298 198.098 56.202 -9.921 re
1241.501 198.098 56.202 -9.921 re
1297.703 198.098 56.202 -9.921 re
836.255 188.177 68.031 -9.921 re
904.287 188.177 56.202 -9.921 re
960.489 188.177 56.202 -9.921 re
1016.691 188.177 56.202 -9.921 re
1072.894 188.177 56.202 -9.921 re
1129.096 188.177 56.202 -9.921 re
1185.298 188.177 56.202 -9.921 re
1241.501 188.177 56.202 -9.921 re
1297.703 188.177 56.202 -9.921 re
836.255 178.256 68.031 -9.921 re
904.287 178.256 56.202 -9.921 re
960.489 178.256 56.202 -9.921 re
1016.691 178.256 56.202 -9.921 re
1072.894 178.256 56.202 -9.921 re
1129.096 178.256 56.202 -9.921 re
1185.298 178.256 56.202 -9.921 re
1241.501 178.256 56.202 -9.921 re
1297.703 178.256 56.202 -9.921 re
836.255 168.335 68.031 -9.921 re
904.287 168.335 56.202 -9.921 re
960.489 168.335 56.202 -9.921 re
1016.691 168.335 56.202 -9.921 re
1072.894 168.335 56.202 -9.921 re
1129.096 168.335 56.202 -9.921 re
1185.298 168.335 56.202 -9.921 re
1241.501 168.335 56.202 -9.921 re
1297.703 168.335 56.202 -9.921 re
836.255 158.413 68.031 -9.921 re
904.287 158.413 56.202 -9.921 re
960.489 158.413 56.202 -9.921 re
1016.691 158.413 56.202 -9.921 re
1072.894 158.413 56.202 -9.921 re
1129.096 158.413 56.202 -9.921 re
1185.298 158.413 56.202 -9.921 re
1241.501 158.413 56.202 -9.921 re
1297.703 158.413 56.202 -9.921 re
836.255 148.492 68.031 -9.921 re
904.287 148.492 56.202 -9.921 re
960.489 148.492 56.202 -9.921 re
1016.691 148.492 56.202 -9.921 re
1072.894 148.492 56.202 -9.921 re
1129.096 148.492 56.202 -9.921 re
1185.298 148.492 56.202 -9.921 re
1241.501 148.492 56.202 -9.921 re
1297.703 148.492 56.202 -9.921 re
836.255 138.571 517.65 -7.814 re
f
0.593 w
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S
Q
q 1 0 0 1 904.2868 246.2272 cm
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S
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0.5 w
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S
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S
Q
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S
Q
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S
Q
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S
Q
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0 0 m
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S
Q
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0 0 m
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S
Q
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0 0 m
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S
Q
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0 0 m
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S
Q
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0 0 m
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S
Q
q 1 0 0 1 1129.0961 148.492 cm
0 0 m
56.202 0 l
S
Q
q 1 0 0 1 1185.2983 148.492 cm
0 0 m
56.202 0 l
S
Q
q 1 0 0 1 1241.5007 148.492 cm
0 0 m
56.202 0 l
S
Q
q 1 0 0 1 1297.703 148.492 cm
0 0 m
55.827 0 l
S
Q
0 0 0 0 K
0.75 w
q 1 0 0 1 904.2868 237.4752 cm
0 0 m
0 8.456 l
S
Q
q 1 0 0 1 1185.2983 237.7252 cm
0 0 m
0 8.206 l
S
Q
0.6 0 0.06 0 K
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0 0 m
68.406 0 l
S
Q
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0 0 m
56.202 0 l
S
Q
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0 0 m
56.202 0 l
S
Q
q 1 0 0 1 1016.6914 138.5708 cm
0 0 m
56.202 0 l
S
Q
q 1 0 0 1 1072.8938 138.5708 cm
0 0 m
56.202 0 l
S
Q
q 1 0 0 1 1129.0961 138.5708 cm
0 0 m
56.202 0 l
S
Q
q 1 0 0 1 1185.2983 138.5708 cm
0 0 m
56.202 0 l
S
Q
q 1 0 0 1 1241.5007 138.5708 cm
0 0 m
56.202 0 l
S
Q
q 1 0 0 1 1297.703 138.5708 cm
0 0 m
56.577 0 l
S
Q
BT
1 0.8 0.38 0.29 k
/GS0 gs
/C2_2 1 Tf
6 0 0 6 836.2551 250.4792 Tm
[<0037>73.9 <00440045004F0048000300180011000300360044004900480057005C000300440051004700030026005200500050005200510003>37.2 <002400470059004800550056004800030028005900480051005700560003004C00510003009500140013000800030052004900030033004400550057004C0046004C0053004400510057005600030053004800550003003300480055004C00520047>]TJ
/TT0 1 Tf
33.367 -1.695 Td
(Part 1)Tj
37.468 0 Td
(Part 2)Tj
-70.362 -4.959 Td
(Adverse event, n \(%\))Tj
15.207 3.5 Td
(A)Tj
-1.88 -1.167 Td
(6.6 mg IN)Tj
0.792 -1.167 Td
(n = 55)Tj
10.159 2.333 Td
(B1)Tj
/C2_2 1 Tf
-2.862 -1.167 Td
<00130011001600030050004A0003002C0030000F000300C00055005600570003>Tj
/TT0 1 Tf
0.056 -1.167 Td
(administration)Tj
2.013 -1.167 Td
(n = 55)Tj
10.159 3.5 Td
(B2)Tj
-3.667 -1.167 Td
(0.3 mg IM, second )Tj
8.684 0 Td
( )Tj
-7.822 -1.167 Td
(administration)Tj
2.013 -1.167 Td
(n = 55)Tj
10.159 3.5 Td
(C1)Tj
/C2_2 1 Tf
-2.862 -1.167 Td
<00130011001800030050004A0003002C0030000F000300C00055005600570003>Tj
/TT0 1 Tf
0.056 -1.167 Td
(administration)Tj
2.013 -1.167 Td
(n = 55)Tj
10.159 3.5 Td
(C2)Tj
-3.667 -1.167 Td
(0.5 mg IM, second )Tj
8.684 0 Td
( )Tj
-7.822 -1.167 Td
(administration)Tj
2.013 -1.167 Td
(n = 55)Tj
10.437 3.5 Td
(D)Tj
-2.835 -1.167 Td
(2 x 6.6 mg IN, )Tj
-0.832 -1.167 Td
(opposite nostrils)Tj
2.597 -1.167 Td
(n = 38)Tj
10.465 3.5 Td
(E)Tj
-2.862 -1.167 Td
(2 x 6.6 mg IN, )Tj
0.25 -1.167 Td
(same nostril)Tj
1.514 -1.167 Td
(n = 40)Tj
10.493 3.5 Td
(F)Tj
-2.946 -1.167 Td
(2 x 0.3 mg IM, )Tj
-0.193 -1.167 Td
(opposite thigh)Tj
2.012 -1.167 Td
(n = 39)Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
-79.688 -1.507 Td
(Nasal discomfort)Tj
14.522 0 Td
(5 \(9\))Tj
10.117 0 Td
(0)Tj
9.367 0 Td
(0)Tj
9.367 0 Td
(0)Tj
9.367 0 Td
(0)Tj
8.339 0 Td
(7 \(18\))Tj
9.367 0 Td
(9 \(23\))Tj
9.645 0 Td
(1 \(3\))Tj
-80.091 -1.654 Td
(Headache)Tj
14.522 0 Td
(4 \(7\))Tj
9.367 0 Td
(2 \(4\))Tj
9.367 0 Td
(1 \(2\))Tj
9.367 0 Td
(3 \(5\))Tj
/Span<>> BDC
( )Tj
EMC
9.367 0 Td
(1 \(2\))Tj
9.367 0 Td
(2 \(5\))Tj
9.089 0 Td
(5 \(13\))Tj
9.645 0 Td
(2 \(5\))Tj
-80.091 -1.654 Td
(Abdominal pain upper)Tj
14.522 0 Td
(2 \(4\))Tj
10.117 0 Td
(0)Tj
9.367 0 Td
(0)Tj
9.367 0 Td
(0)Tj
9.367 0 Td
(0)Tj
8.376 0 Td
[(4 \(1)73.6 (1\))]TJ
9.33 0 Td
(4 \(10\))Tj
10.395 0 Td
(0)Tj
-80.841 -1.654 Td
(Nausea)Tj
14.522 0 Td
(2 \(4\))Tj
10.117 0 Td
(0)Tj
9.367 0 Td
(0)Tj
9.367 0 Td
(0)Tj
9.367 0 Td
(0)Tj
8.617 0 Td
(2 \(5\))Tj
9.089 0 Td
(4 \(10\))Tj
10.395 0 Td
(0)Tj
-80.841 -1.654 Td
(Rhinorrhea)Tj
14.522 0 Td
(1 \(2\))Tj
10.117 0 Td
(0)Tj
8.617 0 Td
(1 \(2\))Tj
10.117 0 Td
(0)Tj
9.367 0 Td
(0)Tj
8.339 0 Td
(5 \(13\))Tj
9.645 0 Td
(1 \(3\))Tj
9.367 0 Td
(2 \(5\))Tj
-80.091 -1.654 Td
[(T)36.8 (remor)]TJ
15.272 0 Td
(0)Tj
8.617 0 Td
(2 \(4\))Tj
9.367 0 Td
(1 \(2\))Tj
9.367 0 Td
(1 \(2\))Tj
9.367 0 Td
(1 \(2\))Tj
9.089 0 Td
(5 \(13\))Tj
9.367 0 Td
(6 \(15\))Tj
9.367 0 Td
(4 \(10\))Tj
-79.813 -1.654 Td
(Pain in extremity)Tj
15.272 0 Td
(0)Tj
8.617 0 Td
(4 \(7\))Tj
9.367 0 Td
(5 \(9\))Tj
9.089 0 Td
(7 \(13\))Tj
9.645 0 Td
(5 \(9\))Tj
10.117 0 Td
(0)Tj
9.367 0 Td
(0)Tj
8.617 0 Td
(3 \(8\))Tj
4.75 0 0 4.75 836.2532 130.7563 Tm
(IM, intramuscular; IN, intranasal.)Tj
ET
0.6 0 0.06 0 k
/GS0 gs
1103.959 393.338 19.843 -8.752 re
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f
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1237.188 321.828 31.181 -8.752 re
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1237.188 313.076 31.181 -8.752 re
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1237.188 304.324 31.181 -8.752 re
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1191.833 295.572 45.354 -8.752 re
1237.188 295.572 31.181 -8.752 re
1268.369 295.572 45.354 -8.752 re
1313.723 295.572 40.182 -8.752 re
1123.802 286.82 22.677 -8.752 re
1146.479 286.82 45.354 -8.752 re
1191.833 286.82 45.354 -8.752 re
1237.188 286.82 31.181 -8.752 re
1268.369 286.82 45.354 -8.752 re
1313.723 286.82 40.182 -8.752 re
1103.959 278.068 249.946 -7.814 re
f
0.593 w
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S
Q
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0.5 w
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S
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Q
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Q
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S
Q
q 1 0 0 1 1146.4789 313.076 cm
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S
Q
q 1 0 0 1 1191.8333 313.076 cm
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S
Q
q 1 0 0 1 1237.1876 313.076 cm
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S
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Q
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S
Q
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S
Q
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q 1 0 0 1 1268.3687 304.324 cm
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Q
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S
Q
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S
Q
q 1 0 0 1 1191.8333 295.5721 cm
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S
Q
q 1 0 0 1 1237.1876 295.5721 cm
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S
Q
q 1 0 0 1 1268.3687 295.5721 cm
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S
Q
q 1 0 0 1 1313.723 295.5721 cm
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S
Q
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S
Q
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S
Q
q 1 0 0 1 1191.8333 286.8201 cm
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S
Q
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S
Q
q 1 0 0 1 1268.3687 286.8201 cm
0 0 m
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S
Q
q 1 0 0 1 1313.723 286.8201 cm
0 0 m
39.807 0 l
S
Q
0 0 0 0 K
0.75 w
q 1 0 0 1 1123.8018 384.5858 cm
0 0 m
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S
Q
q 1 0 0 1 1123.8018 347.8339 cm
0 0 m
0 36.752 l
S
Q
q 1 0 0 1 1146.4789 384.5858 cm
0 0 m
0 8.456 l
S
Q
q 1 0 0 1 1146.4789 347.8339 cm
0 0 m
0 36.752 l
S
Q
q 1 0 0 1 1268.3687 384.8358 cm
0 0 m
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S
Q
0.6 0 0.06 0 K
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S
Q
q 1 0 0 1 1146.4789 278.0681 cm
0 0 m
45.354 0 l
S
Q
q 1 0 0 1 1191.8333 278.0681 cm
0 0 m
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S
Q
q 1 0 0 1 1237.1876 278.0681 cm
0 0 m
31.181 0 l
S
Q
q 1 0 0 1 1268.3687 278.0681 cm
0 0 m
45.354 0 l
S
Q
q 1 0 0 1 1313.723 278.0681 cm
0 0 m
40.557 0 l
S
Q
q 1 0 0 1 1103.5842 278.0681 cm
0 0 m
20.218 0 l
S
Q
BT
1 0.8 0.38 0.29 k
/GS0 gs
/TT0 1 Tf
6 0 0 6 1103.9592 404.5898 Tm
[(T)73.9 (able 4. Percentage of Participants Who Reached Plasma Epinephrine Concen\
trations )]TJ
0 -1.167 Td
(of 100 or 200 pg/mL)Tj
4.039 -5.487 Td
[(T)17.7 (ime )]TJ
-0.063 -1.167 Td
(point )Tj
2.659 0 Td
( )Tj
-2.938 -1.167 Td
(\(mins\))Tj
12.158 6.125 Td
(Part 1)Tj
17.286 0 Td
(Part 2)Tj
0 6 -6 0 1111.2938 352.0858 Tm
(Threshold )Tj
0 -1.167 Td
(\(pg/mL\))Tj
6 0 0 6 1165.3212 378.6685 Tm
(B1)Tj
-1.778 -1.167 Td
(0.3 mg IM, )Tj
5.112 0 Td
( )Tj
/C2_2 1 Tf
-3.64 -1.167 Td
<00C00055005600570003>Tj
/TT0 1 Tf
( )Tj
-2.5 -1.167 Td
(administration)Tj
0.514 -1.167 Td
(n = 55, n \(%\))Tj
9.851 4.667 Td
(B2)Tj
-1.778 -1.167 Td
(0.3 mg IM, )Tj
5.112 0 Td
( )Tj
-4.446 -1.167 Td
(second )Tj
( )Tj
-1.694 -1.167 Td
(administration)Tj
0.514 -1.167 Td
(n = 55, n \(%\))Tj
8.809 4.667 Td
(B, )Tj
( )Tj
-1.139 -1.167 Td
(pooled)Tj
-0.043 -1.167 Td
[(n = 1)55 (10 )]TJ
7.699 2.333 Td
(D)Tj
-2.835 -1.167 Td
(2 x 6.6 mg IN, )Tj
6.565 0 Td
( )Tj
-5.453 -1.167 Td
(opposite)Tj
4.166 0 Td
( )Tj
-4.028 -1.167 Td
( nostrils)Tj
-0.986 -1.167 Td
(n = 38, n \(%\))Tj
9.726 4.667 Td
(E)Tj
-0.04 Tc -2.602 -1.167 Td
[(2 x 6.6 mg IN,)-39.8 ( )]TJ
0 Tc 5.94 0 Td
( )Tj
-4.283 -1.167 Td
(same )Tj
( )Tj
-0.249 -1.167 Td
(nostril)Tj
-1.403 -1.167 Td
(n = 40, n \(%\))Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
-34.906 -3.605 Td
(100)Tj
4.168 2.188 Td
(10)Tj
4.641 0 Td
(41 \(75\))Tj
7.559 0 Td
(41 \(75\))Tj
6.378 0 Td
(82 \(75\))Tj
6.378 0 Td
(33 \(87\))Tj
7.128 0 Td
(33 \(83\))Tj
-32.084 -1.459 Td
(20)Tj
4.641 0 Td
(46 \(84\))Tj
7.559 0 Td
(45 \(82\))Tj
6.378 0 Td
(91 \(83\))Tj
6.378 0 Td
(35 \(92\))Tj
7.128 0 Td
(36 \(90\))Tj
-32.084 -1.459 Td
(30)Tj
4.641 0 Td
(50 \(91\))Tj
7.559 0 Td
(50 \(91\))Tj
6.1 0 Td
(100 \(91\))Tj
6.656 0 Td
(36 \(95\))Tj
7.128 0 Td
(38 \(95\))Tj
-32.084 -1.459 Td
(60)Tj
4.641 0 Td
(53 \(96\))Tj
7.559 0 Td
(51 \(93\))Tj
6.1 0 Td
(104 \(95\))Tj
6.656 0 Td
(36 \(95\))Tj
7.128 0 Td
(38 \(95\))Tj
-36.252 -3.647 Td
(200)Tj
4.168 2.188 Td
(10)Tj
4.641 0 Td
(26 \(47\))Tj
7.559 0 Td
(33 \(60\))Tj
6.378 0 Td
(59 \(54\))Tj
6.378 0 Td
(21 \(55\))Tj
7.128 0 Td
(30 \(75\))Tj
-32.084 -1.459 Td
(20)Tj
4.641 0 Td
(31 \(56\))Tj
7.559 0 Td
(35 \(64\))Tj
6.378 0 Td
(66 \(60\))Tj
6.378 0 Td
(27 \(71\))Tj
7.128 0 Td
(33 \(83\))Tj
-32.084 -1.459 Td
(30)Tj
4.641 0 Td
(39 \(71\))Tj
7.559 0 Td
(37 \(67\))Tj
6.378 0 Td
(76 \(69\))Tj
6.378 0 Td
(28 \(74\))Tj
7.128 0 Td
(37 \(93\))Tj
-32.084 -1.459 Td
(60)Tj
4.641 0 Td
(40 \(73\))Tj
7.559 0 Td
(39 \(71\))Tj
6.378 0 Td
(79 \(72\))Tj
6.378 0 Td
(28 \(74\))Tj
7.128 0 Td
(38 \(95\))Tj
4.75 0 0 4.75 1103.9592 270.2536 Tm
(IM, intramuscular; IN, intranasal. )Tj
ET
1 w
/GS0 gs
q 1 0 0 1 568.1763 523.1378 cm
0 0 m
250.696 0 l
S
Q
BT
1 0.8 0.38 0.29 k
/TT0 1 Tf
8 0 0 8 568.1763 763.3229 Tm
(Pharmacodynamics)Tj
0.6 0 0.06 0 k
/TT1 1 Tf
/Span<>> BDC
7 0 0 7 571.7379 753.9056 Tm
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
[(Cardiovascular ef)16.3 (fects \(heart rate and blood pressure\) were assessed at )]TJ
0 -1.143 Td
(specified times \()Tj
/TT0 1 Tf
7.225 0 Td
(Figure 1B)Tj
/TT1 1 Tf
(\))Tj
1 0.8 0.38 0.29 k
/GS0 gs
/TT0 1 Tf
8 0 0 8 568.1764 732.6536 Tm
(Post hoc analyses)Tj
0.6 0 0.06 0 k
/TT1 1 Tf
/Span<>> BDC
7 0 0 7 571.7379 723.2363 Tm
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(Post hoc analyses compared bioavailability after B \(epinephrine 0.3 mg \
IM\) in )Tj
0 -1.143 Td
(part 1 with D \(epinephrine 2 x 6.6 mg IN, opposite nostrils\) and E \(e\
pinephrine )Tj
0 -1.143 Td
(2 x 6.6 mg IN, same nostril\) in part 2)Tj
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
-0.706 -1.345 Td
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(Post hoc analyses calculated the percentage of participants with plasma \
)Tj
/C2_1 1 Tf
0 -1.143 Td
<00480053004C005100480053004B0055004C0051004800030046005200510046004800510057005500440057004C0052005100560003005200490003001400130013000300520055000300150013001300030053004A00120050002F>Tj
1 0.8 0.38 0.29 k
/GS0 gs
/TT0 1 Tf
8 0 0 8 568.1764 676.567 Tm
(Safety)Tj
0.6 0 0.06 0 k
/TT1 1 Tf
/Span<>> BDC
7 0 0 7 571.7379 667.1497 Tm
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(Adverse events \(AEs\) were monitored and characterized by the Medical )Tj
0 -1.143 Td
[(Dictionary for Regulatory )53.5 (Activities)]TJ
4.081 0 0 4.081 682.8903 661.4807 Tm
(\256)Tj
7 0 0 7 685.8972 659.1497 Tm
( \(version 22.0\))Tj
1 0.8 0.38 0.29 k
/GS0 gs
/TT0 1 Tf
8 0 0 8 568.1764 645.8977 Tm
(Statistical analysis: PK)Tj
0.6 0 0.06 0 k
/TT1 1 Tf
/Span<>> BDC
7 0 0 7 571.7379 636.4803 Tm
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(PK data were analyzed using a noncompartmental approach with Phoenix)Tj
4.081 0 0 4.081 805.8756 638.8113 Tm
(\256)Tj
7 0 0 7 808.8826 636.4803 Tm
( )Tj
-33.172 -1.143 Td
(WinNonlin)Tj
4.081 0 0 4.081 608.5802 630.8113 Tm
(\256)Tj
7 0 0 7 611.5872 628.4803 Tm
( version 7.0 and SAS)Tj
4.081 0 0 4.081 677.3489 630.8113 Tm
(\256)Tj
7 0 0 7 680.3558 628.4803 Tm
( version 9.4)Tj
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
-15.517 -1.345 Td
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(AUC)Tj
4.081 0 0 4.081 591.4596 617.663 Tm
(0\22620)Tj
-0.055 Tw 7 0 0 7 600.5382 619.063 Tm
[( )-54.8 (and )-0.6 (AUC)]TJ
0 Tw 4.081 0 0 4.081 630.5035 617.663 Tm
(0\226360)Tj
7 0 0 7 641.8518 619.063 Tm
( values were estimated by interpolation or extrapolation)Tj
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
-10.016 -1.345 Td
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(T)Tj
4.081 0 0 4.081 580.9562 608.2457 Tm
(max)Tj
7 0 0 7 588.6658 609.6457 Tm
( values were analyzed using nonparametric analysis for paired samples)Tj
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
-2.418 -1.345 Td
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/C2_1 1 Tf
1.215 0 Td
<002C0051000300530052005600570003004B005200460003004400510044004F005C00560048005600030052004900030045004C0052004800540058004C00590044004F0048005100460048000F00030057004B00480003001B00130008000300570052000300140015001800080003004F004C0050004C005700030049005200550003>Tj
/TT1 1 Tf
29.128 0 Td
( )Tj
-0.023 Tc -29.128 -1.143 Td
[(9)-23.1 (0)-23.2 (%)-23.1 ( )-22.9 (confidence interval \(CI\) was used for geometric mean ratios \(GMR\))-23 ( )]TJ
0.6 0 0.06 0 k
/GS0 gs
0 Tc /Span<>> BDC
-0.706 -1.345 Td
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(Baseline-corrected, log-transformed PK parameters were analyzed by )Tj
31.181 0 Td
( )Tj
-31.181 -1.143 Td
[(a generalized linear model and analysis of variance \(ANOV)70.1 (A\) )]TJ
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
-0.706 -1.345 Td
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(Baseline-corrected heart rate and blood pressure measurements for )Tj
0 -1.143 Td
[(maximum positive ef)16.8 (fect concentration \(E)]TJ
4.081 0 0 4.081 704.5533 555.9937 Tm
(max)Tj
7 0 0 7 712.263 557.3937 Tm
(\) were analyzed by SAS )Tj
10.95 0 Td
( )Tj
-30.319 -1.143 Td
[(version 9.4 and )54 (ANOV)73.7 (A)]TJ
1 0.8 0.38 0.29 k
/GS0 gs
/TT0 1 Tf
0.01 Tc -0.01 Tw 13 0 0 13 568.1764 529.3071 Tm
[(RESUL)73.8 (TS)10 ( )]TJ
0.6 0 0.06 0 k
/TT1 1 Tf
0 Tc 0 Tw /Span<>> BDC
7 0 0 7 571.7379 512.8032 Tm
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(Out of 95 total participants, 55 enrolled in part 1 and 40 enrolled in p\
art 2 )Tj
0 -1.143 Td
(\()Tj
/TT0 1 Tf
(Figure 1A)Tj
/TT1 1 Tf
(\))Tj
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
-0.706 -1.345 Td
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(Of those, 2 participants voluntarily withdrew from part 2)Tj
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
-0.706 -1.345 Td
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(In part 1, the average participant age was 33 \261 6 years. In part 2, t\
he average )Tj
0 -1.143 Td
(age was 31 \261 7 years \()Tj
/TT0 1 Tf
[(T)73.9 (able 1)]TJ
/TT1 1 Tf
(\))Tj
ET
q
0 0 1656 792 re
W n
4 M 1 j
/GS0 gs
q 1 0 0 1 -14.1732 429.8477 cm
0 0 m
263.622 0 l
S
Q
Q
BT
0.6 0 0.06 0 k
/GS0 gs
/TT0 1 Tf
-0.01 Tc 11.5 0 0 11.5 34.0158 383.69 Tm
[(Presented at the )36.8 (American )36.8 (Academy of)-10 ( )]TJ
0 -1.217 Td
[(Allergy)73.5 (, )36.8 (Asthma & Immunology \(AAAAI\))-10 ( )]TJ
0 -1.217 Td
[(National Conference, March 16, 2020,)-9.8 ( )]TJ
0 -1.217 Td
[(Philadelphia, P)73.7 (A, USA)]TJ
1 0.8 0.38 0.29 k
0 Tc 8 0 0 8 568.1764 360.7717 Tm
(PK )Tj
0.6 0 0.06 0 k
/TT1 1 Tf
/Span<>> BDC
7 0 0 7 571.7379 351.1043 Tm
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(Double epinephrine IN \(D, epinephrine 2 x 6.6 mg IN, opposite nostrils \
and E, )Tj
0 -1.179 Td
(epinephrine 2 x 6.6 mg IN, same nostril\) resulted in greater C)Tj
4.081 0 0 4.081 766.1588 341.4543 Tm
(max)Tj
7 0 0 7 773.8685 342.8543 Tm
( and )Tj
( )Tj
-28.17 -1.179 Td
(AUC)Tj
4.081 0 0 4.081 591.4596 333.2043 Tm
(0\22620)Tj
7 0 0 7 600.5382 334.6043 Tm
( than single epinephrine IM \(B pooled, 0.3 mg IM\) \(C)Tj
4.081 0 0 4.081 763.1754 333.2043 Tm
(max,)Tj
7 0 0 7 772.0189 334.6043 Tm
( 644 \261 853 )Tj
( )Tj
/C2_1 1 Tf
-27.906 -1.179 Td
[<0044005100470003001400150016001A00030093000300150013001C001C00030059005600030016001A001700030093000300180013001600030053004A00120050002F>35.4 <00030044005100470003>54.6 <002400380026>]TJ
/TT1 1 Tf
4.081 0 0 4.081 722.2687 324.9543 Tm
(0\22620)Tj
7 0 0 7 731.3473 326.3543 Tm
(, 6367 \261 9666 and )Tj
( )Tj
/C2_1 1 Tf
-22.095 -1.179 Td
<00140016000F0016001B001300030093000300150014000F00140016001700030059005600030016001500190016000300930003001500190016001400030050004C0051000D0053004A00120050002F000C0003000B>Tj
/TT0 1 Tf
20.333 0 Td
[(T)73.9 (able 2)]TJ
/TT1 1 Tf
(\))Tj
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
-21.039 -1.381 Td
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
-0.003 Tw 1.215 0 Td
[(Single )-0.7 (epinephrine )-1.4 (IN \(A, epinephrine )-1.5 (6.6 mg IN\) resulted in lower )-0.6 (epinephrine )]TJ
0 Tw 0 -1.179 Td
(exposure than single epinephrine IM \(B, 0.3 mg IM and C, 0.5 mg IM\) )Tj
30.959 0 Td
( )Tj
-30.959 -1.179 Td
(\()Tj
/TT0 1 Tf
[(T)73.9 (able 2)]TJ
/TT1 1 Tf
( and)Tj
/TT0 1 Tf
( Figure 2A)Tj
/TT1 1 Tf
(\) )Tj
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
-0.706 -1.381 Td
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(Double epinephrine IN \(E, epinephrine 2 x 6.6 mg IN, same nostril\) res\
ulted )Tj
33.628 0 Td
( )Tj
-33.628 -1.179 Td
[(in greater exposure than double epinephrine IM \(F)108 (, 2 x 0.3 mg IM\) \()]TJ
/TT0 1 Tf
29.682 0 Td
[(T)73.9 (able 2)]TJ
/TT1 1 Tf
( )Tj
-29.682 -1.179 Td
(and )Tj
/TT0 1 Tf
(Figure 2B)Tj
/TT1 1 Tf
(\))Tj
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
-0.706 -1.381 Td
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(In bioavailability assessments of treatments D \(epinephrine 2 x 6.6 mg \
IN, )Tj
0 -1.179 Td
(opposite nostrils\) and B \(B1 and B2 pooled, 0.3 mg IM\), the GMRs \(90\
% CI\) )Tj
0 -1.179 Td
(for C)Tj
4.081 0 0 4.081 591.8492 238.2024 Tm
(max)Tj
-0.055 Tw 7 0 0 7 599.5589 239.6024 Tm
[( )-54.8 (and )-0.6 (AUC)]TJ
0 Tw 4.081 0 0 4.081 629.5242 238.2024 Tm
(0\226360)Tj
7 0 0 7 640.8725 239.6024 Tm
[( were 145 \(1)73.1 (14\226185\) and 222 \(184\226267\), respectively )]TJ
-9.17 -1.179 Td
(\()Tj
/TT0 1 Tf
[(T)73.9 (able 3)]TJ
/TT1 1 Tf
(\))Tj
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
-0.706 -1.381 Td
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(For treatments E \(epinephrine 2 x 6.6 mg IN, same nostril\) and B \(B1 \
and B2 )Tj
-0.002 Tw 0 -1.179 Td
[(pooled, 0.3 mg IM\), )0.6 (GMRs \(90% CI\) for C)]TJ
0 Tw 4.081 0 0 4.081 705.3223 212.0351 Tm
(max)Tj
-0.057 Tw 7 0 0 7 713.032 213.4351 Tm
[( )-54.8 (and AUC)]TJ
0 Tw 4.081 0 0 4.081 742.9682 212.0351 Tm
(0\226360)Tj
-0.002 Tw 7 0 0 7 754.3165 213.4351 Tm
( were 265 \(209\226337\) )Tj
0 Tw -25.377 -1.179 Td
(and 322 \(274\226379\), respectively \()Tj
/TT0 1 Tf
14.898 0 Td
[(T)73.9 (able 3)]TJ
/TT1 1 Tf
(\))Tj
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
-15.614 -1.381 Td
( )Tj
EMC
/C2_0 1 Tf
-0.499 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
-0.01 Tc 1.215 0 Td
[(A)54.7 ( greater percentage of participants achieved epinephrine concentrations \
of)-9.9 ( )]TJ
/C2_1 1 Tf
0.01 Tw 0 -1.179 Td
[<0014001300130003004400510047000300150013001300030053004A00120050002F>36.4 <0003004400490057004800550003005700550048004400570050004800510057000300280003000B00480053004C005100480053004B0055004C00510048000300150003005B000300190011001900030050004A0003002C0031000F00030056004400500048000300510052005600570055004C004F000C>-10 <0003>]TJ
/TT1 1 Tf
0 Tw 0 -1.179 Td
[(in part 2 compared with treatment B \(B1 and B2 pooled, 0.3 mg IM\) in p\
art 1,)-9.8 ( )]TJ
/C2_1 1 Tf
0.01 Tw 0 -1.179 Td
[<0048005B004600480053005700030044005700030019001300030050004C00510058005700480056000F0003005A004B0048005100030057004B0048000300530048005500460048005100570044004A0048000300440046004B004C00480059004C0051004A000300140013001300030053004A00120050002F>36.5 <0003005A0044005600030057004B004800030056004400500048>-10.1 <0003>]TJ
/TT1 1 Tf
0 Tc 0 Tw 0 -1.179 Td
(\()Tj
/TT0 1 Tf
-0.01 Tc 0.323 0 Td
[(T)73.9 (able 4)]TJ
/TT1 1 Tf
0 Tc (\))Tj
1 0.8 0.38 0.29 k
/GS0 gs
/TT0 1 Tf
8 0 0 8 568.1764 149.2658 Tm
(Pharmacodynamics)Tj
0.6 0 0.06 0 k
/TT1 1 Tf
/Span<>> BDC
7 0 0 7 571.7379 139.5984 Tm
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
[(There were no dif)16.8 (ferences in average E)]TJ
4.081 0 0 4.081 699.1256 138.1984 Tm
(max)Tj
7 0 0 7 706.8353 139.5984 Tm
( for heart rate among groups in )Tj
14.008 0 Td
( )Tj
-32.601 -1.179 Td
(part 1 \(mean \261 SD E)Tj
4.081 0 0 4.081 640.4357 129.9484 Tm
(max)Tj
7 0 0 7 648.1453 131.3484 Tm
[(, )55 (A)54.7 ( [epinephrine 6.6 mg IN]: 24 \261 15; B1 [epinephrine )]TJ
-10.209 -1.179 Td
(0.3 mg IM]: 23 \261 12; B2 [epinephrine 0.3 mg IM]: 23 \261 14; C1 [epin\
ephrine )Tj
32.95 0 Td
( )Tj
-0.015 Tc -32.95 -1.179 Td
[(0.5 mg IM]: 25 \261 14; C2 [epinephrine 0.5 mg IM]: 25 \261 18 beats per\
minute \(bpm\))-15 ( )]TJ
0.6 0 0.06 0 k
/GS0 gs
0 Tc /Span<>> BDC
-0.726 -1.381 Td
( )Tj
EMC
/C2_0 1 Tf
-0.489 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
-0.02 Tc 1.215 0 Td
[(There were no dif)17.8 (ferences in mean heart rate among groups in part 1 \()]TJ
/TT0 1 Tf
(Figure 3A)Tj
/TT1 1 Tf
0 Tc (\))Tj
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
-0.706 -1.381 Td
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
(In part 2, mean heart rate was slightly increased after E \(epinephrine \
2 x )Tj
32.239 0 Td
( )Tj
-32.239 -1.179 Td
(6.6 mg IN, same nostril\) compared with D \(2 x 6.6 mg IN, opposite nost\
rils\) or )Tj
0 -1.179 Td
(F \(0.3 mg IM, opposite thighs\) \()Tj
/TT0 1 Tf
(Figure 3B)Tj
/TT1 1 Tf
(\))Tj
0.6 0 0.06 0 k
/GS0 gs
/Span<>> BDC
-0.731 -1.381 Td
( )Tj
EMC
/C2_0 1 Tf
-0.484 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
-0.025 Tc 1.215 0 Td
[(There were no dif)17.7 (ferences in mean systolic blood pressure in part 1 or 2 \()]TJ
/TT0 1 Tf
(Figure 4)Tj
/TT1 1 Tf
0 Tc (\))Tj
1 0.8 0.38 0.29 k
/GS0 gs
/TT0 1 Tf
8 0 0 8 568.1764 56.0945 Tm
(Safety)Tj
0.6 0 0.06 0 k
/TT1 1 Tf
/Span<>> BDC
7 0 0 7 571.7379 46.6772 Tm
( )Tj
EMC
/C2_0 1 Tf
-0.509 0 Td
<0069>Tj
0 0 0 1 k
/GS1 gs
/TT1 1 Tf
1.215 0 Td
[(The most common )54.6 (AE reported after IN epinephrine was nasal discomfort. )]TJ
0 -1.143 Td
[(The most common )54.6 (AEs after IM epinephrine were pain in extremity with B1, )]TJ
0 -1.143 Td
(B2, C1, and C2 \(epinephrine 0.3 mg and 0.5 mg IM\) and tremor with F )Tj
31.349 0 Td
( )Tj
-31.349 -1.143 Td
(\(2 x 0.3 mg IM\) \()Tj
/TT0 1 Tf
7.334 0 Td
[(T)73.9 (able 5)]TJ
/TT1 1 Tf
(\))Tj
ET
0.293 w
/GS2 gs
q 1 0 0 1 551.3412 65.024 cm
0 0 m
0 215.088 l
S
Q
0.241 w
q 1 0 0 1 300.4724 280.2323 cm
0 0 m
251.016 0 l
S
Q
q 1 0 0 1 300.4724 64.9033 cm
0 0 m
251.016 0 l
S
Q
0.346 w
q 1 0 0 1 300.6452 65.024 cm
0 0 m
0 215.088 l
S
Q
BT
1 0.8 0.38 0.29 k
/GS0 gs
/TT0 1 Tf
6 0 0 6 300.6452 284.4843 Tm
(Figure 1. Participant Disposition \(A\) and Study Design \(B\) )Tj
ET
/PlacedGraphic /MC3 BDC
EMC
0 0 0 1 k
q 1 0 0 1 367.2504 241.8714 cm
0 0 m
148.414 0 l
h
f
Q
0 0 0 1 K
0.3 w
q 1 0 0 1 367.2502 241.871 cm
0 0 m
0.5 0 l
S
Q
[1.003 1.003]0 d
q 1 0 0 1 368.7526 241.871 cm
0 0 m
145.91 0 l
S
Q
[]0 d
q 1 0 0 1 515.1638 241.871 cm
0 0 m
0.5 0 l
S
Q
q 1 0 0 1 367.2504 235.17 cm
0 0 m
148.414 0 l
h
f
Q
q 1 0 0 1 367.2502 235.1704 cm
0 0 m
0.5 0 l
S
Q
[1.003 1.003]0 d
q 1 0 0 1 368.7526 235.1704 cm
0 0 m
145.91 0 l
S
Q
[]0 d
q 1 0 0 1 515.1638 235.1704 cm
0 0 m
0.5 0 l
S
Q
q 1 0 0 1 367.2504 228.4695 cm
0 0 m
148.414 0 l
h
f
Q
q 1 0 0 1 367.2502 228.4697 cm
0 0 m
0.5 0 l
S
Q
[1.003 1.003]0 d
q 1 0 0 1 368.7526 228.4697 cm
0 0 m
145.91 0 l
S
Q
[]0 d
q 1 0 0 1 515.1638 228.4697 cm
0 0 m
0.5 0 l
S
Q
q 1 0 0 1 367.2504 221.7681 cm
0 0 m
148.414 0 l
h
f
Q
q 1 0 0 1 367.2502 221.7684 cm
0 0 m
0.5 0 l
S
Q
[1.003 1.003]0 d
q 1 0 0 1 368.7526 221.7684 cm
0 0 m
145.91 0 l
S
Q
[]0 d
q 1 0 0 1 515.1638 221.7684 cm
0 0 m
0.5 0 l
S
Q
q 1 0 0 1 367.2504 215.0676 cm
0 0 m
148.414 0 l
h
f
Q
q 1 0 0 1 367.2502 215.0678 cm
0 0 m
0.5 0 l
S
Q
[1.003 1.003]0 d
q 1 0 0 1 368.7526 215.0678 cm
0 0 m
145.91 0 l
S
Q
[]0 d
q 1 0 0 1 515.1638 215.0678 cm
0 0 m
0.5 0 l
S
Q
0.6 0 0.06 0 k
367.25 239.343 -6.227 5.056 re
f
0.5 w 2 J
q 1 0 0 1 364.1364 254.8637 cm
0 0 m
0 3.261 l
154.641 3.261 l
154.641 0 l
S
Q
0 0 0 1 k
q 1 0 0 1 365.1335 255.1552 cm
0 0 m
-0.997 -1.727 l
-1.995 0 l
h
f
Q
q 1 0 0 1 517.7808 255.1552 cm
0 0 m
0.997 -1.727 l
1.994 0 l
h
f
Q
q 1 0 0 1 402.7966 254.8637 cm
0 0 m
0 3.261 l
S
Q
q 1 0 0 1 403.7936 255.1552 cm
0 0 m
-0.997 -1.727 l
-1.994 0 l
h
f
Q
q 1 0 0 1 441.4568 267.8583 cm
0 0 m
0 3.261 l
S
Q
q 1 0 0 1 442.4538 268.1498 cm
0 0 m
-0.997 -1.727 l
-1.994 0 l
h
f
Q
q 1 0 0 1 441.4568 164.5423 cm
0 0 m
0 3.26 l
S
Q
q 1 0 0 1 442.4538 164.8342 cm
0 0 m
-0.997 -1.728 l
-1.994 0 l
h
f
Q
q 1 0 0 1 488.6178 178.3007 cm
0 0 m
-5.387 0 l
S
Q
q 1 0 0 1 488.3268 179.2977 cm
0 0 m
1.727 -0.997 l
0 -1.994 l
h
f
Q
q 1 0 0 1 441.4568 254.8637 cm
0 0 m
0 5.833 l
S
Q
q 1 0 0 1 442.4538 255.1552 cm
0 0 m
-0.997 -1.727 l
-1.994 0 l
h
f
Q
q 1 0 0 1 480.1168 254.8637 cm
0 0 m
0 3.261 l
S
Q
q 1 0 0 1 481.1148 255.1552 cm
0 0 m
-0.997 -1.727 l
-1.995 0 l
h
f
Q
BT
/T1_6 1 Tf
5 0 0 5 421.3768 272.3949 Tm
(Screened, N = 95)Tj
-23.03 0 Td
(A.)Tj
9.609 -4.985 Td
(Period )Tj
(1)Tj
/T1_7 1 Tf
-9.609 -1.326 Td
(Sequence 1, n = 11)Tj
0 -1.378 Td
(Sequence 2, n = 11)Tj
0 -1.378 Td
(Sequence 3, n = 11)Tj
7.732 -8.638 Td
(Sequence 1, n = 13)Tj
0 -1.378 Td
(Sequence 2, n = 15)Tj
2.915 0 0 2.915 388.3933 178.6503 Tm
(a)Tj
5 0 0 5 344.8854 170.0972 Tm
(Sequence 3, n = 12)Tj
-7.732 10.016 Td
(Sequence 4, n = 11)Tj
0 -1.378 Td
(Sequence 5, n = 11)Tj
/T1_8 1 Tf
4 0 0 4 377.3283 251.5029 Tm
(\0371 day)Tj
-0.327 -1 Td
(washout)Tj
9.993 1 Td
(\0371 day)Tj
-0.328 -1 Td
(washout)Tj
9.993 1 Td
(\0371 day)Tj
-0.328 -1 Td
(washout)Tj
9.993 1 Td
(\0371 day)Tj
-0.327 -1 Td
(washout)Tj
/T1_6 1 Tf
5 0 0 5 362.3298 240.0926 Tm
(A)Tj
ET
0.328 0.4 0.072 0.048 k
367.25 232.642 -6.227 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 362.3298 233.3921 Tm
(B)Tj
ET
0.328 0.4 0.072 0.048 k
367.25 225.942 -6.227 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 362.3298 226.6913 Tm
(B)Tj
ET
0 0 0 0.344 k
367.25 219.241 -6.227 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 362.3298 219.9906 Tm
(C)Tj
ET
0 0 0 0.344 k
367.25 212.54 -6.227 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 362.3298 213.2894 Tm
(C)Tj
ET
0.328 0.4 0.072 0.048 k
405.91 239.343 -6.228 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 392.9318 247.4692 Tm
(Period )Tj
(2)Tj
1.612 -1.475 Td
(B)Tj
ET
0.328 0.4 0.072 0.048 k
405.91 232.642 -6.228 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 400.9904 233.3921 Tm
(B)Tj
ET
0 0 0 0.344 k
405.91 225.942 -6.228 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 400.9904 226.6913 Tm
(C)Tj
ET
0 0 0 0.344 k
405.91 219.241 -6.228 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 400.9904 219.9906 Tm
(C)Tj
ET
0.6 0 0.06 0 k
405.91 212.54 -6.228 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 400.9904 213.2894 Tm
(A)Tj
ET
0 0 0 0.344 k
444.571 239.343 -6.227 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 431.5928 247.4692 Tm
(Period )Tj
3.39 0 Td
(3)Tj
-1.778 -1.475 Td
(C)Tj
ET
0.6 0 0.06 0 k
444.571 232.642 -6.227 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 439.6508 233.3921 Tm
(A)Tj
ET
0.328 0.4 0.072 0.048 k
444.571 225.942 -6.227 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 439.6508 226.6913 Tm
(B)Tj
ET
0.328 0.4 0.072 0.048 k
444.571 219.241 -6.227 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 439.6508 219.9906 Tm
(B)Tj
ET
0 0 0 0.344 k
444.571 212.54 -6.227 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 439.6508 213.2894 Tm
(C)Tj
ET
0.328 0.4 0.072 0.048 k
483.231 239.343 -6.227 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 470.2528 247.4692 Tm
(Period )Tj
3.39 0 Td
(4)Tj
-1.778 -1.475 Td
(B)Tj
ET
0 0 0 0.344 k
483.231 232.642 -6.227 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 478.3108 233.3921 Tm
(C)Tj
ET
0 0 0 0.344 k
483.231 225.942 -6.227 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 478.3108 226.6913 Tm
(C)Tj
ET
0.6 0 0.06 0 k
483.231 219.241 -6.227 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 478.3108 219.9906 Tm
(A)Tj
ET
0.328 0.4 0.072 0.048 k
483.231 212.54 -6.227 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 478.3108 213.2894 Tm
(B)Tj
ET
0 0 0 0.344 k
521.892 239.343 -6.228 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 508.9128 247.4692 Tm
(Period )Tj
(5)Tj
1.612 -1.475 Td
(C)Tj
ET
0 0 0 0.344 k
521.892 232.642 -6.228 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 516.9718 233.3921 Tm
(C)Tj
ET
0.6 0 0.06 0 k
521.892 225.942 -6.228 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 516.9718 226.6913 Tm
(A)Tj
ET
0.328 0.4 0.072 0.048 k
521.892 219.241 -6.228 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 516.9718 219.9906 Tm
(B)Tj
ET
0.328 0.4 0.072 0.048 k
521.892 212.54 -6.228 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 516.9718 213.2894 Tm
(B)Tj
/T1_9 1 Tf
-20.009 9.737 Td
(Entered Part 1, n = 55)Tj
ET
q 1 0 0 1 405.9099 184.9032 cm
0 0 m
71.094 0 l
h
f
Q
0.3 w 0 J
q 1 0 0 1 405.9103 184.9032 cm
0 0 m
0.501 0 l
S
Q
[0.987 0.987]0 d
q 1 0 0 1 407.3978 184.9032 cm
0 0 m
68.613 0 l
S
Q
[]0 d
q 1 0 0 1 476.5038 184.9032 cm
0 0 m
0.5 0 l
S
Q
q 1 0 0 1 405.9099 178.2018 cm
0 0 m
71.094 0 l
h
f
Q
q 1 0 0 1 405.9103 178.202 cm
0 0 m
0.501 0 l
S
Q
[0.987 0.987]0 d
q 1 0 0 1 407.3978 178.202 cm
0 0 m
68.613 0 l
S
Q
[]0 d
q 1 0 0 1 476.5038 178.202 cm
0 0 m
0.5 0 l
S
Q
q 1 0 0 1 405.9099 171.5022 cm
0 0 m
71.094 0 l
h
f
Q
q 1 0 0 1 405.9103 171.5023 cm
0 0 m
0.501 0 l
S
Q
[0.987 0.987]0 d
q 1 0 0 1 407.3978 171.5023 cm
0 0 m
68.613 0 l
S
Q
[]0 d
q 1 0 0 1 476.5038 171.5023 cm
0 0 m
0.5 0 l
S
Q
0.5 w 2 J
q 1 0 0 1 402.7961 197.0459 cm
0 0 m
0 3.261 l
77.321 3.261 l
77.321 0 l
S
Q
q 1 0 0 1 403.7932 197.3368 cm
0 0 m
-0.997 -1.727 l
-1.994 0 l
h
f
Q
q 1 0 0 1 479.1198 197.3368 cm
0 0 m
0.997 -1.727 l
1.995 0 l
h
f
Q
q 1 0 0 1 441.4568 197.0459 cm
0 0 m
0 5.832 l
S
Q
q 1 0 0 1 442.4538 197.3368 cm
0 0 m
-0.997 -1.727 l
-1.994 0 l
h
f
Q
BT
/T1_8 1 Tf
4 0 0 4 415.9888 194.1098 Tm
(\0371 day)Tj
-0.328 -1 Td
(washout)Tj
9.992 1.106 Td
(\0371 day)Tj
-0.328 -1 Td
(washout)Tj
ET
0.205 0.25 0.045 0.03 k
405.91 182.375 -6.228 5.057 re
f
BT
0 0 0 1 k
/T1_6 1 Tf
5 0 0 5 392.9318 190.5018 Tm
(Period )Tj
(1)Tj
1.612 -1.475 Td
(D)Tj
ET
0.3 0 0.03 0 k
406.008 175.772 -6.227 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 401.1286 176.4243 Tm
(E)Tj
ET
0.3 0.24 0.114 0.087 k
405.91 168.973 -6.228 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 401.2687 169.7233 Tm
(F)Tj
ET
0.3 0 0.03 0 k
444.669 182.474 -6.228 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 431.5928 190.5018 Tm
(Period )Tj
3.39 0 Td
(2)Tj
-1.75 -1.475 Td
(E)Tj
ET
0.3 0.24 0.114 0.087 k
444.571 175.674 -6.227 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 439.9288 176.4243 Tm
(F)Tj
ET
0.205 0.25 0.045 0.03 k
444.571 168.973 -6.227 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 439.6508 169.7233 Tm
(D)Tj
ET
0.3 0.24 0.114 0.087 k
483.231 182.375 -6.227 5.057 re
f
BT
0 0 0 1 k
5 0 0 5 470.2528 190.5018 Tm
(Period )Tj
3.39 0 Td
(3)Tj
-1.722 -1.475 Td
(F)Tj
ET
0.205 0.25 0.045 0.03 k
483.231 175.674 -6.227 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 478.3108 176.4243 Tm
(D)Tj
ET
0.3 0 0.03 0 k
483.329 169.072 -6.228 5.056 re
f
BT
0 0 0 1 k
5 0 0 5 478.4498 169.7233 Tm
(E)Tj
/T1_9 1 Tf
-12.305 6.886 Td
(Entered Part 2, n = 40)Tj
-0.667 -9.145 Td
(Completed Part 2, n = 38)Tj
4.5 0 0 4.5 497.3178 181.9491 Tm
(Discontinued prior to)Tj
-0.585 -1.111 Td
(dosing in periods 2 and)Tj
0.07 -1.111 Td
(3 for AEs = 2, replaced)Tj
ET
545.788 186.679 -55.667 -16.854 re
545.488 170.124 -55.067 16.255 re
f
BT
/GS1 gs
/TT1 1 Tf
2.7692 0 0 2.7692 300.6452 58.6706 Tm
(a)Tj
/C2_1 1 Tf
4.75 0 0 4.75 302.1853 57.0888 Tm
<00320051004800030053004400550057004C0046004C00530044005100570003005A004B00520003005A004400560003005500440051004700520050004C005D00480047000300570052000300570055004800440057005000480051005700030056004800540058004800510046004800030028002900270003005A0044005600030047005200560048004700030044005600030027002900280003004C0051000300480055005500520055>Tj
41.021 0 Td
<0011>Tj
/TT1 1 Tf
2.7692 0 0 2.7692 300.6452 52.4206 Tm
(b)Tj
4.75 0 0 4.75 302.1853 50.8388 Tm
[(Performed at end of part 1 and part 2 or prior to early termination from\
study)72.3 (. )]TJ
2.7692 0 0 2.7692 300.6452 46.1706 Tm
(c)Tj
-0.01 Tc -0.001 Tw 4.75 0 0 4.75 302.0021 44.5888 Tm
[(The )0.7 (clinical )0.7 (research )0.7 (unit )0.7 (followed )0.7 (up )0.7 (approximately )0.7 (7 )0.7 (days )0.7 (after )0.7 (the )0.7 (last )0.7 (study )0.7 (drug )0.7 (administration )0.7 (for )0.7 (information )0.7 (on )55.4 (AEs.)]TJ
0 Tc 0 Tw -0.286 -1.316 Td
[(A, epinephrine 6.6 mg IN; )54 (AE, adverse event; B1, epinephrine 0.3 mg IM via EpiPen)]TJ
2.7692 0 0 2.7692 476.764 39.9206 Tm
(\256)Tj
/C2_1 1 Tf
4.75 0 0 4.75 478.8044 38.3388 Tm
<000300C00055005600570003004400470050004C0051004C00560057005500440057004C00520051001E000300250015000F0003>Tj
/TT1 1 Tf
-37.507 -1.105 Td
[(epinephrine 0.3 mg IM via EpiPen second administration; BP)126.1 (, blood pressure; C1, epinephrine 0.5 mg IM via manual )]TJ
/C2_1 1 Tf
0 -1.105 Td
<0056005C0055004C0051004A0048000300C00055005600570003004400470050004C0051004C00560057005500440057004C00520051001E000300260015000F000300480053004C005100480053004B0055004C00510048000300130011001800030050004A0003002C003000030059004C0044000300500044005100580044004F00030056005C0055004C0051004A004800030056004800460052005100470003004400470050004C0051004C00560057005500440057004C00520051001E000300280037>Tj
44.298 0 Td
<000F0003004800440055004F005C00030057004800550050004C005100440057004C00520051001E0003>Tj
/TT1 1 Tf
-44.298 -1.105 Td
(HR, heart rate; PK, pharmacokinetics; S, screening.)Tj
ET
0 0 0 0 k
/GS0 gs
306.142 70.083 240.678 71.876 re
f
0.6 0 0.06 0 k
306.292 141.808 45.354 -8.821 re
351.646 141.808 8.504 -22.443 re
360.15 141.808 11.339 -8.821 re
371.489 141.808 153.071 -8.821 re
524.559 141.808 11.339 -22.443 re
535.898 141.808 10.772 -22.443 re
306.292 132.987 45.354 -13.621 re
360.15 132.987 11.339 -13.621 re
371.489 132.987 8.504 -13.621 re
379.992 132.987 8.504 -13.621 re
388.496 132.987 8.504 -13.621 re
397 132.987 8.504 -13.621 re
405.504 132.987 8.504 -13.621 re
414.008 132.987 8.504 -13.621 re
422.512 132.987 8.504 -13.621 re
431.016 132.987 8.504 -13.621 re
439.52 132.987 8.504 -13.621 re
448.024 132.987 8.504 -13.621 re
456.528 132.987 8.504 -13.621 re
465.032 132.987 8.504 -13.621 re
473.536 132.987 8.504 -13.621 re
482.04 132.987 8.504 -13.621 re
490.544 132.987 8.504 -13.621 re
499.048 132.987 8.504 -13.621 re
507.552 132.987 8.504 -13.621 re
516.055 132.987 8.504 -13.621 re
f
0.3 0 0.03 0 K
0.3 w 0 J
/GS2 gs
q 1 0 0 1 306.4417 119.366 cm
0 0 m
45.204 0 l
S
Q
q 1 0 0 1 351.6461 119.366 cm
0 0 m
8.504 0 l
S
Q
q 1 0 0 1 360.15 119.366 cm
0 0 m
11.339 0 l
S
Q
q 1 0 0 1 371.4886 119.366 cm
0 0 m
8.504 0 l
S
Q
q 1 0 0 1 379.9925 119.366 cm
0 0 m
8.504 0 l
S
Q
q 1 0 0 1 388.4965 119.366 cm
0 0 m
8.504 0 l
S
Q
q 1 0 0 1 397.0004 119.366 cm
0 0 m
8.504 0 l
S
Q
q 1 0 0 1 405.5043 119.366 cm
0 0 m
8.504 0 l
S
Q
q 1 0 0 1 414.0083 119.366 cm
0 0 m
8.504 0 l
S
Q
q 1 0 0 1 422.5122 119.366 cm
0 0 m
8.504 0 l
S
Q
q 1 0 0 1 431.0161 119.366 cm
0 0 m
8.504 0 l
S
Q
q 1 0 0 1 439.5201 119.366 cm
0 0 m
8.504 0 l
S
Q
q 1 0 0 1 448.024 119.366 cm
0 0 m
8.504 0 l
S
Q
q 1 0 0 1 456.528 119.366 cm
0 0 m
8.504 0 l
S
Q
q 1 0 0 1 465.0319 119.366 cm
0 0 m
8.504 0 l
S
Q
q 1 0 0 1 473.5358 119.366 cm
0 0 m
8.504 0 l
S
Q
q 1 0 0 1 482.0397 119.366 cm
0 0 m
8.504 0 l
S
Q
q 1 0 0 1 490.5437 119.366 cm
0 0 m
8.504 0 l
S
Q
q 1 0 0 1 499.0476 119.366 cm
0 0 m
8.504 0 l
S
Q
q 1 0 0 1 507.5516 119.366 cm
0 0 m
8.504 0 l
S
Q
q 1 0 0 1 516.0555 119.366 cm
0 0 m
8.504 0 l
S
Q
q 1 0 0 1 524.5594 119.366 cm
0 0 m
11.339 0 l
S
Q
q 1 0 0 1 535.898 119.366 cm
0 0 m
10.622 0 l
S
Q
q 1 0 0 1 306.4417 108.5793 cm
0 0 m
45.054 0 l
S
Q
q 1 0 0 1 351.7961 108.5793 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 360.3 108.5793 cm
0 0 m
11.039 0 l
S
Q
q 1 0 0 1 371.6386 108.5793 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 380.1425 108.5793 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 388.6465 108.5793 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 397.1504 108.5793 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 405.6543 108.5793 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 414.1583 108.5793 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 422.6622 108.5793 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 431.1661 108.5793 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 439.6701 108.5793 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 448.174 108.5793 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 456.6779 108.5793 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 465.1819 108.5793 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 473.6858 108.5793 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 482.1898 108.5793 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 490.6937 108.5793 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 499.1976 108.5793 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 507.7016 108.5793 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 516.2055 108.5793 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 524.7095 108.5793 cm
0 0 m
11.039 0 l
S
Q
q 1 0 0 1 536.048 108.5793 cm
0 0 m
10.472 0 l
S
Q
q 1 0 0 1 306.4417 92.9927 cm
0 0 m
45.054 0 l
S
Q
q 1 0 0 1 351.7961 92.9927 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 360.3 92.9927 cm
0 0 m
11.039 0 l
S
Q
q 1 0 0 1 371.6386 92.9927 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 380.1425 92.9927 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 388.6465 92.9927 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 397.1504 92.9927 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 405.6543 92.9927 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 414.1583 92.9927 cm
0 0 m
8.204 0 l
S
Q
q 1 0 0 1 422.6622 92.9927 cm
0 0 m
8.204 0 l
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(S)Tj
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