Trial Outcomes & Findings for Epinephrine Inhalation Aerosol USP, a HFA-MDI Study for Assessment of Pharmacokinetics (NCT NCT01188577)
NCT ID: NCT01188577
Last Updated: 2017-07-25
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.
COMPLETED
PHASE1/PHASE2
23 participants
0 to 30 minutes prior to dosing
2017-07-25
Participant Flow
Participants were recruited from a specialty clinic in Cypress, CA between 08/19/2010 and 09/09/2010.
A total of 35 subjects were screened, 23 subjects passed screening, consented and were randomized for participation in the study.
Participant milestones
| Measure |
C, T
Subjects received one of the two 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 T: Ten (10) inhalations of E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min.
|
T, C
Subjects received one of the two treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T: Ten (10) inhalations of 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 1
STARTED
|
11
|
12
|
|
Visit 1
COMPLETED
|
11
|
12
|
|
Visit 1
NOT COMPLETED
|
0
|
0
|
|
3-14 Day Washout
STARTED
|
11
|
12
|
|
3-14 Day Washout
COMPLETED
|
11
|
12
|
|
3-14 Day Washout
NOT COMPLETED
|
0
|
0
|
|
Visit 2
STARTED
|
11
|
12
|
|
Visit 2
COMPLETED
|
11
|
12
|
|
Visit 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Epinephrine Inhalation Aerosol USP, a HFA-MDI Study for Assessment of Pharmacokinetics
Baseline characteristics by cohort
| Measure |
C, T
n=11 Participants
Subjects received one of the two 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 T: Ten (10) inhalations of E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min.
|
T, C
n=12 Participants
Subjects received one of the two treatments during each study visit, separated by a washout period of 3-14 days. Visit 1: Treatment T: Ten (10) inhalations of 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.
|
Total
n=23 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
22.8 Years
STANDARD_DEVIATION 2.99 • n=99 Participants
|
24.8 Years
STANDARD_DEVIATION 2.93 • n=107 Participants
|
23.8 Years
STANDARD_DEVIATION 3.05 • n=206 Participants
|
|
Age, Categorical
<=18 years
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
10 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
22 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
11 participants
n=99 Participants
|
12 participants
n=107 Participants
|
23 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 0 to 30 minutes prior to dosingPopulation: 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 three of the four post-dose PK measurement btwn 2 and 10 min post-dose available and 4) have a minimum of twelve of the fifteen 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
| Measure |
Treatment T
n=23 Participants
Ten (10) inhalations of E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min
|
Treatment C
n=23 Participants
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min
|
|---|---|---|
|
Baseline Concentration (C0) of Total Epinephrine
|
2.6 pg/mL
Standard Deviation 8.7
|
4.3 pg/mL
Standard Deviation 16.7
|
PRIMARY outcome
Timeframe: Pre-dose to 6 hours post-dosePopulation: 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 three of the four post-dose PK measurements btw 2 and 10 min post-dose available and 4) have a minimum of twelve of the fifteen 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), 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 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
| Measure |
Treatment T
n=23 Participants
Ten (10) inhalations of E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min
|
Treatment C
n=23 Participants
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min
|
|---|---|---|
|
Peak Concentration (Cmax) of Total Epinephrine From Time Zero to 6 Hours Post-dose
|
862 pg/mL
Standard Deviation 527
|
190 pg/mL
Standard Deviation 119
|
PRIMARY outcome
Timeframe: Pre-dose to 6 hours post-dosePopulation: 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 three of the four post-dose PK measurements btw 2 and 10 min post-dose available and 4) have a minimum of twelve of the fifteen 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), 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 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
| Measure |
Treatment T
n=23 Participants
Ten (10) inhalations of E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min
|
Treatment C
n=23 Participants
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min
|
|---|---|---|
|
Area Under the Curve From Time Zero to 6 Hours Post-dose (AUC[0-6]) for Total Epinephrine
|
8498 pg*min/mL
Standard Deviation 5213
|
6191 pg*min/mL
Standard Deviation 4108
|
PRIMARY outcome
Timeframe: Pre-dose to 6 hours post-dosePopulation: 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 three of the four post-dose PK measurements btw 2 and 10 min post-dose available and 4) have a minimum of twelve of the fifteen 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), 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 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
| Measure |
Treatment T
n=23 Participants
Ten (10) inhalations of E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min
|
Treatment C
n=23 Participants
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min
|
|---|---|---|
|
Time to Reach Peak Concentration (Tmax) for Total Epinephrine
|
2.3 min
Standard Deviation 1.7
|
3.4 min
Standard Deviation 4.3
|
PRIMARY outcome
Timeframe: Pre-dose to 6 hours post-dosePopulation: 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 three of the four post-dose PK measurements btw 2 and 10 min post-dose available and 4) have a minimum of twelve of the fifteen 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), 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 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 to decrease to half the peak concentration in plasma during the treatment period.
Outcome measures
| Measure |
Treatment T
n=23 Participants
Ten (10) inhalations of E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min
|
Treatment C
n=23 Participants
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min
|
|---|---|---|
|
Half-life (t1/2) of Total Epinephrine
|
145.9 min
Interval 1.7 to 864.0
|
289.8 min
Interval 1.8 to 1996.3
|
PRIMARY outcome
Timeframe: Pre-dose to 6 hours post-dosePopulation: 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 three of the four post-dose PK measurements btw 2 and 10 min post-dose available and 4) have a minimum of twelve of the fifteen 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), 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240, and 360 minutes post-dose in each treatment period and were analyzed using an established analysis method.
Outcome measures
| Measure |
Treatment T
n=23 Participants
Ten (10) inhalations of E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min
|
Treatment C
n=23 Participants
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min
|
|---|---|---|
|
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
0 min (Baseline)
|
2.6 pg/mL
Standard Deviation 8.7
|
4.3 pg/mL
Standard Deviation 16.7
|
|
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
2 min post-dose
|
861.5 pg/mL
Standard Deviation 528.2
|
189.0 pg/mL
Standard Deviation 123.3
|
|
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
5 min post-dose
|
379.4 pg/mL
Standard Deviation 203.0
|
99.1 pg/mL
Standard Deviation 67.0
|
|
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
7.5 min post-dose
|
186.6 pg/mL
Standard Deviation 97.7
|
48.8 pg/mL
Standard Deviation 30.0
|
|
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
10 min post-dose
|
118.3 pg/mL
Standard Deviation 65.8
|
39.7 pg/mL
Standard Deviation 22.9
|
|
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
12.5 min post-dose
|
75.6 pg/mL
Standard Deviation 42.2
|
33.9 pg/mL
Standard Deviation 21.4
|
|
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
15 min post-dose
|
46.8 pg/mL
Standard Deviation 41.7
|
32.0 pg/mL
Standard Deviation 23.3
|
|
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
20 min post-dose
|
22.9 pg/mL
Standard Deviation 21.3
|
30.1 pg/mL
Standard Deviation 19.8
|
|
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
25 min post-dose
|
10.9 pg/mL
Standard Deviation 19.9
|
20.3 pg/mL
Standard Deviation 17.9
|
|
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
30 min post-dose
|
10.5 pg/mL
Standard Deviation 16.1
|
17.7 pg/mL
Standard Deviation 19.4
|
|
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
45 min post-dose
|
10.5 pg/mL
Standard Deviation 22.5
|
19.8 pg/mL
Standard Deviation 21.2
|
|
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
60 min post-dose
|
8.7 pg/mL
Standard Deviation 13.9
|
13.2 pg/mL
Standard Deviation 14.5
|
|
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
90 min post-dose
|
3.5 pg/mL
Standard Deviation 9.4
|
11.2 pg/mL
Standard Deviation 18.2
|
|
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
120 min post-dose
|
6.5 pg/mL
Standard Deviation 13.2
|
6.9 pg/mL
Standard Deviation 12.0
|
|
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
240 min post-dose
|
16.1 pg/mL
Standard Deviation 23.8
|
17.7 pg/mL
Standard Deviation 17.6
|
|
Concentration vs. Time for Total Epinephrine From Time Zero to 6 Hours Post-dose
360 min post-dose
|
17.1 pg/mL
Standard Deviation 23.9
|
17.2 pg/mL
Standard Deviation 20.4
|
Adverse Events
Treatment T
Treatment C
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment T
n=23 participants at risk
Ten (10) inhalations of E004 (125 mcg/inhalation), totaling 1.25 mg of epinephrine, in 5 min
|
Treatment C
n=23 participants at risk
Ten(10) inhalations of Epinephrine CFC-MDI (220 mcg/inhalation), totaling 2.20 mg of epinephrine, in 5 min
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
4.3%
1/23 • Number of events 1 • Throughout entire study period
|
0.00%
0/23 • Throughout entire study period
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/23 • Throughout entire study period
|
4.3%
1/23 • Number of events 1 • Throughout entire study period
|
|
Respiratory, thoracic and mediastinal disorders
Viral Upper Respiratory Tract Infection
|
0.00%
0/23 • Throughout entire study period
|
4.3%
1/23 • Number of events 1 • Throughout entire study period
|
Additional Information
Stephen A. Campbell, Esq.
Amphastar Pharmaceuticals, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER