Trial Outcomes & Findings for Pharmacokinetics (PK) Study of Epinephrine Inhalation Aerosol in Healthy Volunteers (NCT NCT01143051)

NCT ID: NCT01143051

Last Updated: 2018-09-25

Results Overview

Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at Baseline (prior to dosing) in each treatment period following a specified washout period (3-14 days), and were analyzed using an established analysis method. Baseline concentration (C0) is the concentration of epinephrine measured in the plasma at this time point.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

24 participants

Primary outcome timeframe

0 to 30 minutes prior to dosing

Results posted on

2018-09-25

Participant Flow

Participants were recruited from a specialty clinic in Cypress, CA between 04/29/2010 and 05/27/2010

A total of 38 subjects were screened, 24 subjects passed screening, consented and were randomized for participation in the study. The IRB approval date was 04/29/2010, the last subject was screened on 05/27/2010.

Participant milestones

Participant milestones
Measure
C, T1, T2
Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 2: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 3: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min.
C, T2, T1
Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 2: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 3: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min.
T1, C, T2
Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 2: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 3: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min.
T1, T2, C
Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 2: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 3: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min.
T2, C, T1
Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 2: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 3: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min.
T2, T1, C
Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 2: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 3 Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min.
Visit 1
STARTED
4
4
4
4
4
4
Visit 1
COMPLETED
4
4
4
4
4
4
Visit 1
NOT COMPLETED
0
0
0
0
0
0
3-14 Day Washout
STARTED
4
4
3
4
4
4
3-14 Day Washout
COMPLETED
4
4
3
4
4
3
3-14 Day Washout
NOT COMPLETED
0
0
0
0
0
1
Visit 2
STARTED
4
4
3
4
4
4
Visit 2
COMPLETED
4
4
3
4
4
4
Visit 2
NOT COMPLETED
0
0
0
0
0
0
Visit 3
STARTED
4
4
3
4
4
3
Visit 3
COMPLETED
4
4
3
4
4
3
Visit 3
NOT COMPLETED
0
0
0
0
0
0

Reasons for withdrawal

Reasons for withdrawal
Measure
C, T1, T2
Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 2: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 3: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min.
C, T2, T1
Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 2: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 3: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min.
T1, C, T2
Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 2: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 3: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min.
T1, T2, C
Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 2: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 3: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min.
T2, C, T1
Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 2: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 3: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min.
T2, T1, C
Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 2: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 3 Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min.
3-14 Day Washout
Withdrawal by Subject
0
0
0
0
0
1

Baseline Characteristics

Pharmacokinetics (PK) Study of Epinephrine Inhalation Aerosol in Healthy Volunteers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
C, T1, T2
n=4 Participants
Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 2: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 3: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min.
C, T2, T1
n=4 Participants
Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 2: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 3: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min.
T1, C, T2
n=4 Participants
Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 2: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 3: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min.
T1, T2, C
n=4 Participants
Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 2: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 3: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min.
T2, C, T1
n=4 Participants
Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 2: Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min; Visit 3: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min.
T2, T1, C
n=4 Participants
Subjects received one of the three treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T2: Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine, in 5 min; Visit 2: Treatment T1: Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min; Visit 3 Treatment C: Ten (10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min.
Total
n=24 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
0 Participants
n=8 Participants
0 Participants
n=8 Participants
Age, Categorical
Between 18 and 65 years
4 Participants
n=5 Participants
4 Participants
n=7 Participants
4 Participants
n=5 Participants
4 Participants
n=4 Participants
4 Participants
n=21 Participants
4 Participants
n=8 Participants
24 Participants
n=8 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
0 Participants
n=8 Participants
0 Participants
n=8 Participants
Age, Continuous
24.0 years
STANDARD_DEVIATION 2.94 • n=5 Participants
25.3 years
STANDARD_DEVIATION 4.27 • n=7 Participants
24.0 years
STANDARD_DEVIATION 3.37 • n=5 Participants
21.8 years
STANDARD_DEVIATION 1.71 • n=4 Participants
25.3 years
STANDARD_DEVIATION 0.50 • n=21 Participants
22.0 years
STANDARD_DEVIATION 3.56 • n=8 Participants
23.7 years
STANDARD_DEVIATION 3.01 • n=8 Participants
Sex: Female, Male
Female
1 Participants
n=5 Participants
2 Participants
n=7 Participants
1 Participants
n=5 Participants
2 Participants
n=4 Participants
1 Participants
n=21 Participants
2 Participants
n=8 Participants
9 Participants
n=8 Participants
Sex: Female, Male
Male
3 Participants
n=5 Participants
2 Participants
n=7 Participants
3 Participants
n=5 Participants
2 Participants
n=4 Participants
3 Participants
n=21 Participants
2 Participants
n=8 Participants
15 Participants
n=8 Participants
Region of Enrollment
United States
4 participants
n=5 Participants
4 participants
n=7 Participants
4 participants
n=5 Participants
4 participants
n=4 Participants
4 participants
n=21 Participants
4 participants
n=8 Participants
24 participants
n=8 Participants

PRIMARY outcome

Timeframe: 0 to 30 minutes prior to dosing

Population: Patients who: 1) have taken the valid pre-dose baseline PK sample 2) have correctly taken the randomized study-drug treatment 3) have at least four of the five post-dose PK measurements between 5 and 60 min post-dose available and 4) have a minimum of eight of the ten post-dose PK measurements for the entire 6 hour post-dose PK sampling period.

Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at Baseline (prior to dosing) in each treatment period following a specified washout period (3-14 days), and were analyzed using an established analysis method. Baseline concentration (C0) is the concentration of epinephrine measured in the plasma at this time point.

Outcome measures

Outcome measures
Measure
Treatment T1
n=24 Participants
Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine
Treatment T2
n=22 Participants
Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine
Treatment C
n=22 Participants
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine
Baseline Concentration (C0) of Labeled Epinephrine Total Epinephrine
9.3 pg/mL
Standard Deviation 17.7
8.9 pg/mL
Standard Deviation 15.8
7.8 pg/mL
Standard Deviation 21.4

PRIMARY outcome

Timeframe: Pre-dose to 6 hours post-dose

Population: Patients who: 1) have taken the valid pre-dose baseline PK sample 2) have correctly taken the randomized study-drug treatment 3) have at least four of the five post-dose PK measurements between 5 and 60 min post-dose available and 4) have a minimum of eight of the ten post-dose PK measurements for the entire 6 hour post-dose PK sampling period.

Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Area under the curve from time zero to 6 hours post-dose (AUC\[0-6\]) was calculated using the trapezoidal rule.

Outcome measures

Outcome measures
Measure
Treatment T1
n=24 Participants
Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine
Treatment T2
n=22 Participants
Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine
Treatment C
n=22 Participants
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine
Area Under the Curve From Time Zero to 6 Hours Post-dose (AUC[0-6])
7938 pg*min/mL
Standard Deviation 5023
9438 pg*min/mL
Standard Deviation 4819
7218 pg*min/mL
Standard Deviation 6489

PRIMARY outcome

Timeframe: Pre-dose to 6 hours post-dose

Population: Patients who: 1) have taken the valid pre-dose baseline PK sample 2) have correctly taken the randomized study-drug treatment 3) have at least four of the five post-dose PK measurements between 5 and 60 min post-dose available and 4) have a minimum of eight of the ten post-dose PK measurements for the entire 6 hour post-dose PK sampling period.

Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Peak (maximum) concentration (Cmax) is the highest concentration of epinephrine measured in plasma during the treatment period.

Outcome measures

Outcome measures
Measure
Treatment T1
n=24 Participants
Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine
Treatment T2
n=22 Participants
Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine
Treatment C
n=22 Participants
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine
Peak Concentration (Cmax) for Total Epinephrine From Time Zero to 6 Hours Post-dose
340 pg/mL
Standard Deviation 294
444 pg/mL
Standard Deviation 328
139 pg/mL
Standard Deviation 98

PRIMARY outcome

Timeframe: Pre-dose to 6 hours post-dose

Population: Patients who : 1) have taken the valid pre-dose baseline PK sample 2) have correctly taken the randomized study-drug treatment 3) have at least four of the five post-dose PK measurements between 5 and 60 min post-dose available and 4) have a minimum of eight of the ten post-dose PK measurements for the entire 6 hour post-dose PK sampling period.

Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. tmax is the amount of time it takes for epinephrine to reach peak concentration in plasma during the treatment period.

Outcome measures

Outcome measures
Measure
Treatment T1
n=24 Participants
Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine
Treatment T2
n=22 Participants
Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine
Treatment C
n=22 Participants
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine
Time to Reach Peak Concentration (Tmax) for Total Epinephrine
34.6 min
Standard Deviation 100.2
37.0 min
Standard Deviation 104.5
38.0 min
Standard Deviation 104.3

PRIMARY outcome

Timeframe: Pre-dose to 6 hours post-dose

Population: Patients who: 1) have taken the valid pre-dose baseline PK sample 2) have correctly taken the randomized study-drug treatment 3) have at least 4 of the 5 post-dose PK measurements between 5 and 60 min post-dose available; and 4) have a min of 8 of the 10 post-dose PK measurements for the entire 6 hour post-dose PK sampling period.

Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method. Half-life (t1/2) is the amount of time it takes for epinephrine decrease to half the peak concentration in plasma during the treatment period.

Outcome measures

Outcome measures
Measure
Treatment T1
n=24 Participants
Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine
Treatment T2
n=22 Participants
Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine
Treatment C
n=22 Participants
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine
Half-life (t1/2) for Total Epinephrine
125.9 min
Full Range 183.3 • Interval 10.8 to 337.3
158.8 min
Full Range 238.0 • Interval 3.1 to 432.8
237.3 min
Full Range 175.2 • Interval 6.8 to 490.2

PRIMARY outcome

Timeframe: Pre-dose to 6 hours post-dose

Population: Patients who : 1) have taken the valid pre-dose baseline PK sample 2) have correctly taken the randomized study-drug treatment 3) have at least 4 of the 5 post-dose PK measurements between 5 and 60 minutes post-dose available and 4) have a min of 8 of the 10 post-dose PK measurements for the entire 6 hour post-dose PK sampling period.

Patient PK blood samples were taken from a vein in a hand or arm via indwelling heparin-anticoagulated IV catheters, or by venipunctures at 0 (baseline), 5, 15, 30, 45, 60, 90, 120, 180, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method.

Outcome measures

Outcome measures
Measure
Treatment T1
n=24 Participants
Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine
Treatment T2
n=22 Participants
Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine
Treatment C
n=22 Participants
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
Total Epinephrine, 0 min (Baseline)
9.3 pg/mL
Standard Deviation 17.7
8.9 pg/mL
Standard Deviation 15.8
7.8 pg/mL
Standard Deviation 21.4
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
Total Epinephrine, 5 min post-dose
339.6 pg/mL
Standard Deviation 295.1
442.4 pg/mL
Standard Deviation 330.8
130.2 pg/mL
Standard Deviation 101.8
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
Total Epinephrine, 15 min post-dose
48.9 pg/mL
Standard Deviation 33.7
62.4 pg/mL
Standard Deviation 42.5
38.5 pg/mL
Standard Deviation 21.2
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
Total Epinephrine, 30 min post-dose
12.7 pg/mL
Standard Deviation 18.8
17.4 pg/mL
Standard Deviation 18.3
16.8 pg/mL
Standard Deviation 17.6
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
Total Epinephrine, 45 min post-dose
8.6 pg/mL
Standard Deviation 14.4
13.0 pg/mL
Standard Deviation 17.2
20.9 pg/mL
Standard Deviation 18.6
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
Total Epinephrine, 60 min post-dose
7.6 pg/mL
Standard Deviation 14.7
14.5 pg/mL
Standard Deviation 17.3
18.0 pg/mL
Standard Deviation 18.6
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
Total Epinephrine, 90 min post-dose
5.7 pg/mL
Standard Deviation 11.6
13.7 pg/mL
Standard Deviation 14.8
16.7 pg/mL
Standard Deviation 16.6
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
Total Epinephrine, 120 min post-dose
8.7 pg/mL
Standard Deviation 12.8
15.5 pg/mL
Standard Deviation 19.7
13.1 pg/mL
Standard Deviation 17.6
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
Total Epinephrine, 180 min post-dose
12.0 pg/mL
Standard Deviation 20.2
10.4 pg/mL
Standard Deviation 15.2
8.4 pg/mL
Standard Deviation 15.2
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
Total Epinephrine, 240 min post-dose
12.9 pg/mL
Standard Deviation 20.4
11.5 pg/mL
Standard Deviation 14.9
9.8 pg/mL
Standard Deviation 18.1
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
Total Epinephrine, 360 min post-dose
31.1 pg/mL
Standard Deviation 24.0
29.4 pg/mL
Standard Deviation 23.0
38.3 pg/mL
Standard Deviation 40.8

SECONDARY outcome

Timeframe: Pre-dose (baseline) to 360 minutes post-dose

Population: Subjects who have taken any amount of study drug treatment.

Subject vital signs, i.e., blood pressure and heart rate, were measured prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit.

Outcome measures

Outcome measures
Measure
Treatment T1
n=24 Participants
Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine
Treatment T2
n=23 Participants
Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine
Treatment C
n=22 Participants
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine
Vital Signs: Systolic Blood Pressure (SBP)
Pre-dose (Baseline)
110 mmHg
Standard Deviation 10.0
112 mmHg
Standard Deviation 13.2
111 mmHg
Standard Deviation 9.4
Vital Signs: Systolic Blood Pressure (SBP)
10 min post-dose
123 mmHg
Standard Deviation 13.8
122 mmHg
Standard Deviation 14.1
121 mmHg
Standard Deviation 11.3
Vital Signs: Systolic Blood Pressure (SBP)
30 min post-dose
116 mmHg
Standard Deviation 12.3
117 mmHg
Standard Deviation 11.5
116 mmHg
Standard Deviation 10.6
Vital Signs: Systolic Blood Pressure (SBP)
60 min post-dose
113 mmHg
Standard Deviation 11.2
113 mmHg
Standard Deviation 9.9
115 mmHg
Standard Deviation 10.0
Vital Signs: Systolic Blood Pressure (SBP)
120 min post-dose
112 mmHg
Standard Deviation 10.4
114 mmHg
Standard Deviation 9.6
114 mmHg
Standard Deviation 10.9
Vital Signs: Systolic Blood Pressure (SBP)
180 min post-dose
114 mmHg
Standard Deviation 10.1
113 mmHg
Standard Deviation 11.4
115 mmHg
Standard Deviation 11.0
Vital Signs: Systolic Blood Pressure (SBP)
360 min post-dose
113 mmHg
Standard Deviation 9.8
113 mmHg
Standard Deviation 9.3
113 mmHg
Standard Deviation 9.5

SECONDARY outcome

Timeframe: Pre-dose (baseline) to 360 minutes post-dose

Population: Subjects who have taken any amount of study drug treatment.

Subject vital signs, i.e., blood pressure and heart rate, were measured prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit.

Outcome measures

Outcome measures
Measure
Treatment T1
n=24 Participants
Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine
Treatment T2
n=23 Participants
Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine
Treatment C
n=22 Participants
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine
Vital Signs: Diastolic Blood Pressure (DBP)
Pre-dose (Baseline)
62 mmHg
Standard Deviation 9.3
61 mmHg
Standard Deviation 11.2
61 mmHg
Standard Deviation 10.8
Vital Signs: Diastolic Blood Pressure (DBP)
10 min post-dose
63 mmHg
Standard Deviation 10.1
64 mmHg
Standard Deviation 10.0
65 mmHg
Standard Deviation 10.2
Vital Signs: Diastolic Blood Pressure (DBP)
30 min post-dose
64 mmHg
Standard Deviation 11.2
64 mmHg
Standard Deviation 9.2
65 mmHg
Standard Deviation 9.5
Vital Signs: Diastolic Blood Pressure (DBP)
60 min post-dose
63 mmHg
Standard Deviation 10.8
64 mmHg
Standard Deviation 10.4
63 mmHg
Standard Deviation 8.8
Vital Signs: Diastolic Blood Pressure (DBP)
120 min post-dose
61 mmHg
Standard Deviation 9.8
63 mmHg
Standard Deviation 11.9
62 mmHg
Standard Deviation 10.6
Vital Signs: Diastolic Blood Pressure (DBP)
180 min post-dose
62 mmHg
Standard Deviation 8.3
60 mmHg
Standard Deviation 9.5
59 mmHg
Standard Deviation 7.5
Vital Signs: Diastolic Blood Pressure (DBP)
360 min post-dose
62 mmHg
Standard Deviation 8.8
62 mmHg
Standard Deviation 10.1
62 mmHg
Standard Deviation 8.0

SECONDARY outcome

Timeframe: Pre-dose (baseline) to 360 minutes post-dose

Population: Subjects who have taken any amount of study drug treatment.

Subject vital signs, i.e., blood pressure and heart rate, were measured prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit.

Outcome measures

Outcome measures
Measure
Treatment T1
n=24 Participants
Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine
Treatment T2
n=23 Participants
Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine
Treatment C
n=22 Participants
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine
Vital Signs: Heart Rate (HR)
Pre-dose (Baseline)
60 beats per minute
Standard Deviation 10.1
62 beats per minute
Standard Deviation 12.2
58 beats per minute
Standard Deviation 11.7
Vital Signs: Heart Rate (HR)
10 min post-dose
67 beats per minute
Standard Deviation 14.0
69 beats per minute
Standard Deviation 12.2
62 beats per minute
Standard Deviation 12.7
Vital Signs: Heart Rate (HR)
30 min post-dose
63 beats per minute
Standard Deviation 14.2
64 beats per minute
Standard Deviation 9.8
61 beats per minute
Standard Deviation 13.7
Vital Signs: Heart Rate (HR)
60 min post-dose
67 beats per minute
Standard Deviation 12.9
67 beats per minute
Standard Deviation 14.4
61 beats per minute
Standard Deviation 10.8
Vital Signs: Heart Rate (HR)
120 min post-dose
60 beats per minute
Standard Deviation 10.1
60 beats per minute
Standard Deviation 7.1
58 beats per minute
Standard Deviation 9.4
Vital Signs: Heart Rate (HR)
180 min post-dose
66 beats per minute
Standard Deviation 11.1
66 beats per minute
Standard Deviation 10.5
63 beats per minute
Standard Deviation 9.9
Vital Signs: Heart Rate (HR)
360 min post-dose
64 beats per minute
Standard Deviation 8.7
64 beats per minute
Standard Deviation 10.4
61 beats per minute
Standard Deviation 8.4

SECONDARY outcome

Timeframe: Pre-dose (baseline) to 360 minutes post-dose

Population: Subjects who have taken any amount of study drug treatment.

Subject QT and QTc Intervals were recorded using a 12-Lead ECG prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit.

Outcome measures

Outcome measures
Measure
Treatment T1
n=24 Participants
Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine
Treatment T2
n=23 Participants
Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine
Treatment C
n=22 Participants
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine
ECG: QT Interval
Pre-dose (Baseline)
416 msec
Standard Deviation 33.6
407 msec
Standard Deviation 30.1
423 msec
Standard Deviation 44.1
ECG: QT Interval
30 min post-dose
404 msec
Standard Deviation 38.6
405 msec
Standard Deviation 32.8
413 msec
Standard Deviation 44.8
ECG: QT Interval
90 min post-dose
399 msec
Standard Deviation 34.3
401 msec
Standard Deviation 32.9
407 msec
Standard Deviation 41.3
ECG: QT Interval
360 min post-dose
399 msec
Standard Deviation 41.5
400 msec
Standard Deviation 33.1
400 msec
Standard Deviation 37.7

SECONDARY outcome

Timeframe: Pre-dose (baseline) to 360 minutes post-dose

Population: Subjects who have taken any amount of study drug treatment.

Subject QT and QTc Intervals were recorded using a 12-Lead ECG prior to study drug dosing (baseline) and up to 360 minutes after dosing during the study visit.

Outcome measures

Outcome measures
Measure
Treatment T1
n=24 Participants
Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine
Treatment T2
n=23 Participants
Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine
Treatment C
n=22 Participants
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine
ECG: QTc Interval
Pre-dose (Baseline)
407 msec
Standard Deviation 16.9
407 msec
Standard Deviation 20.0
403 msec
Standard Deviation 16.2
ECG: QTc Interval
30 min post-dose
408 msec
Standard Deviation 15.2
411 msec
Standard Deviation 19.4
412 msec
Standard Deviation 22.3
ECG: QTc Interval
90 min post-dose
401 msec
Standard Deviation 16.9
401 msec
Standard Deviation 18.1
403 msec
Standard Deviation 14.1
ECG: QTc Interval
360 min post-dose
403 msec
Standard Deviation 18.2
403 msec
Standard Deviation 17.9
402 msec
Standard Deviation 15.7

SECONDARY outcome

Timeframe: Pre-dose (baseline) to 360 minutes post-dose

Population: Subjects who have taken any amount of study drug treatment.

Blood samples used to measure subject serum glucose and potassium levels were collected prior to study drug dosing (baseline) and up to 360 minutes post-dose.

Outcome measures

Outcome measures
Measure
Treatment T1
n=24 Participants
Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine
Treatment T2
n=23 Participants
Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine
Treatment C
n=22 Participants
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine
Serum Glucose Levels
Pre-dose (Baseline)
83 mg/dL
Standard Deviation 6.9
83 mg/dL
Standard Deviation 9.1
84 mg/dL
Standard Deviation 6.2
Serum Glucose Levels
15 min post-dose
101 mg/dL
Standard Deviation 17.0
105 mg/dL
Standard Deviation 11.6
96 mg/dL
Standard Deviation 11.0
Serum Glucose Levels
30 min post-dose
94 mg/dL
Standard Deviation 16.4
99 mg/dL
Standard Deviation 12.1
98 mg/dL
Standard Deviation 10.7
Serum Glucose Levels
60 min post-dose
86 mg/dL
Standard Deviation 8.9
86 mg/dL
Standard Deviation 10.8
94 mg/dL
Standard Deviation 12.5
Serum Glucose Levels
120 min post-dose
81 mg/dL
Standard Deviation 6.8
82 mg/dL
Standard Deviation 6.1
83 mg/dL
Standard Deviation 5.3
Serum Glucose Levels
360 min post-dose
82 mg/dL
Standard Deviation 7.9
82 mg/dL
Standard Deviation 9.4
80 mg/dL
Standard Deviation 7.1

SECONDARY outcome

Timeframe: Pre-dose (baseline) to 360 minutes post-dose

Population: Subjects who have taken any amount of study drug treatment.

Blood samples used to measure subject serum glucose and potassium levels were collected prior to study drug dosing (baseline) and up to 360 minutes post-dose.

Outcome measures

Outcome measures
Measure
Treatment T1
n=24 Participants
Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine
Treatment T2
n=23 Participants
Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine
Treatment C
n=22 Participants
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine
Serum Potassium Levels
Pre-dose (Baseline)
4 mmol/L
Standard Deviation 0.2
4 mmol/L
Standard Deviation 0.3
4 mmol/L
Standard Deviation 0.2
Serum Potassium Levels
15 min post-dose
4 mmol/L
Standard Deviation 0.3
4 mmol/L
Standard Deviation 0.3
4 mmol/L
Standard Deviation 0.3
Serum Potassium Levels
30 min post-dose
4 mmol/L
Standard Deviation 0.5
4 mmol/L
Standard Deviation 0.3
4 mmol/L
Standard Deviation 0.3
Serum Potassium Levels
60 min post-dose
4 mmol/L
Standard Deviation 0.2
4 mmol/L
Standard Deviation 0.3
4 mmol/L
Standard Deviation 0.2
Serum Potassium Levels
120 min post-dose
4 mmol/L
Standard Deviation 0.3
4 mmol/L
Standard Deviation 0.3
4 mmol/L
Standard Deviation 0.3
Serum Potassium Levels
360 min post-dose
4 mmol/L
Standard Deviation 0.3
4 mmol/L
Standard Deviation 0.3
4 mmol/L
Standard Deviation 0.2

SECONDARY outcome

Timeframe: Pre-dose (baseline) to 360 minutes post-dose

Population: Subjects who have taken any amount of study drug treatment.

Subjects evaluated hand tremor experiences using a scale from 0 to 3 (0: No tremor; 1: Mild, perceivable; 2: Moderate, observable; and 3: Severe, interfering with hand activities). Hand tremors were evaluated prior to study drug dosing (baseline) and up to 360 minutes post-dose.

Outcome measures

Outcome measures
Measure
Treatment T1
n=24 Participants
Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine
Treatment T2
n=23 Participants
Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine
Treatment C
n=22 Participants
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine
Hand Tremor Scores
60 min post-dose
0.0 score on a scale
Standard Deviation 0.0
0.0 score on a scale
Standard Deviation 0.0
0.0 score on a scale
Standard Deviation 0.2
Hand Tremor Scores
Pre-dose (Baseline)
0.0 score on a scale
Standard Deviation 0.0
0.0 score on a scale
Standard Deviation 0.0
0.0 score on a scale
Standard Deviation 0.0
Hand Tremor Scores
10 min post-dose
0.1 score on a scale
Standard Deviation 0.3
0.2 score on a scale
Standard Deviation 0.4
0.1 score on a scale
Standard Deviation 0.4
Hand Tremor Scores
360 min post-dose
0.0 score on a scale
Standard Deviation 0.0
0.0 score on a scale
Standard Deviation 0.0
0.0 score on a scale
Standard Deviation 0.2

SECONDARY outcome

Timeframe: Approximately 6 weeks

Population: Subjects who have taken any amount of study drug treatment. The Arm/Group is presented as one group because subjects would have received all 3 different study drug treatments prior to EOS due to the crossover study design.

Physical examinations were performed as a part of Screening and End-of-Study (EOS) procedures. This outcome is a count of the number of subjects that showed a clinically significant change in the EOS physical examination compared to the Screening Visit.

Outcome measures

Outcome measures
Measure
Treatment T1
n=24 Participants
Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine
Treatment T2
Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine
Treatment C
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine
Number of Subjects With Significant Changes in Physical Examination
0 Participants

SECONDARY outcome

Timeframe: Approximately 6 weeks

Population: Subjects who have taken any amount of study drug treatment. The Arm/Group is presented as one group because subjects would have received all 3 different study drug treatments prior to EOS due to the crossover study design.

Laboratory tests (CBC, serum comprehensive metabolic panel, urinalysis, and urinary pregnancy test for women of childbearing potential) were performed as a part of Screening and End-of-Study (EOS) procedures. This outcome is a count of the number of subjects that showed a clinically significant change in the EOS laboratory tests compared to the Screening Visit.

Outcome measures

Outcome measures
Measure
Treatment T1
n=24 Participants
Ten (10) inhalations of the low dose E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine
Treatment T2
Ten (10) inhalations of the high dose E004 (160 mcg/inhalation), totaling 1.60 mg of epinephrine
Treatment C
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine
Number of Subjects With Significant Changes in Laboratory Tests
0 Participants

Adverse Events

Treatment T1

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Treatment T2

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Treatment C

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Treatment T1
n=24 participants at risk
T1 is HFA propelled epinephrine inhalation aerosol 125 mcg/inhalation epinephrine inhalation aerosol : HFA propelled epinephrine inhalation aerosol, 125 mcg/inhalation, 10 inhalations
Treatment T2
n=23 participants at risk
HFA propelled epinephrine inhalation aerosol, 160 mcg/inhalation epinephrine inhalation aerosol : HFA propelled epinephrine inhalation aerosol, 160 mcg/inhalation, 10 inhalations
Treatment C
n=22 participants at risk
Active comparator arm utilizing marketed Primatene Mist with CFC propellant at the labeled dose. epinephrine inhalation aerosol : Single dose 220 mcg/inhalation, 10 inhalations
Gastrointestinal disorders
Nausea
4.2%
1/24 • Number of events 1 • All patients were closely monitored for any incidence of adverse events by the investigators during the entire study period.
0.00%
0/23 • All patients were closely monitored for any incidence of adverse events by the investigators during the entire study period.
4.5%
1/22 • Number of events 1 • All patients were closely monitored for any incidence of adverse events by the investigators during the entire study period.
Gastrointestinal disorders
Vomiting
4.2%
1/24 • Number of events 1 • All patients were closely monitored for any incidence of adverse events by the investigators during the entire study period.
0.00%
0/23 • All patients were closely monitored for any incidence of adverse events by the investigators during the entire study period.
0.00%
0/22 • All patients were closely monitored for any incidence of adverse events by the investigators during the entire study period.
Gastrointestinal disorders
Upset stomach
0.00%
0/24 • All patients were closely monitored for any incidence of adverse events by the investigators during the entire study period.
4.3%
1/23 • Number of events 1 • All patients were closely monitored for any incidence of adverse events by the investigators during the entire study period.
0.00%
0/22 • All patients were closely monitored for any incidence of adverse events by the investigators during the entire study period.
Gastrointestinal disorders
Sore throat
0.00%
0/24 • All patients were closely monitored for any incidence of adverse events by the investigators during the entire study period.
0.00%
0/23 • All patients were closely monitored for any incidence of adverse events by the investigators during the entire study period.
4.5%
1/22 • Number of events 1 • All patients were closely monitored for any incidence of adverse events by the investigators during the entire study period.
Nervous system disorders
Lightheadedness
0.00%
0/24 • All patients were closely monitored for any incidence of adverse events by the investigators during the entire study period.
0.00%
0/23 • All patients were closely monitored for any incidence of adverse events by the investigators during the entire study period.
4.5%
1/22 • Number of events 1 • All patients were closely monitored for any incidence of adverse events by the investigators during the entire study period.

Additional Information

Stephen A. Campbell, Esq.

Amphastar Pharmaceuticals, Inc.

Phone: (909) 980-9484

Results disclosure agreements

  • Principal investigator is a sponsor employee The PI is to maintain all information, data, inventions and discoveries disclosed by the Sponsor in confidence unless that information was in public domain at time of disclosure or becomes part of the public domain or is published through no fault of the PI or Institution, or was in the possession of the PI or Institution at time of disclosure and was not acquired from Sponsor under any obligation of confidentiality or is produced pursuant to a validly issued subpoena.
  • Publication restrictions are in place

Restriction type: OTHER