Trial Outcomes & Findings for Study of Drug Exposure in Systemic Circulation of Primatene Mist by Oral Inhalation, Versus Epinephrine Injection by Intramuscular Injection and ProAir by Oral Inhalation in Healthy Individuals (NCT NCT04207840)
NCT ID: NCT04207840
Last Updated: 2021-03-30
Results Overview
Pharmacokinetic (PK) blood samples will be collected starting 30 minutes before dose and until 24 hours after dose. Plasma will be isolated for analyzing the concentrations of Albuterol and Epinephrine. C\[max\] will be obtained directly from the plot of PK curve.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
28 participants
Primary outcome timeframe
Samples were drawn at 30 minutes pre-dose and at 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 25, 30, 40, 50, 60, 70, 80, 90, 120 minutes, 4, 6, 8, 12, 18, and 24 hours post-dose.
Results posted on
2021-03-30
Participant Flow
Participants were randomized to receive all 3 treatments over 3 treatment periods in a crossover design.
Participant milestones
| Measure |
A-B-C
Subjects received one of the three treatments during each study visit. Visit 1: Treatment A: Two (2) inhalations of Primatene Mist (0.125 mg of epinephrine per inhalation), for a total dosage of 0.25 mg; Visit 2: Treatment B: Intramuscular injection of Epinephrine via Auto-Injector (0.30 mg of epinephrine solution in 0.30 mL), for a total dosage of 0.30 mg; Visit 3: Treatment C: Two (2) inhalations of Albuterol HFA (0.09 mg of albuterol sulfate per inhalation), for a total dosage of 0.18 mg.
|
B-C-A
Subjects received one of the three treatments during each study visit. Visit 1: Treatment B: Intramuscular injection of Epinephrine via Auto-Injector (0.30 mg of epinephrine solution in 0.30 mL), for a total dosage of 0.30 mg; Visit 2: Treatment C: Two (2) inhalations of Albuterol HFA (0.09 mg of albuterol sulfate per inhalation), for a total dosage of 0.18 mg; Visit 3: Treatment A: Two (2) inhalations of Primatene Mist (0.125 mg of epinephrine per inhalation), for a total dosage of 0.25 mg.
|
C-A-B
Subjects received one of the three treatments during each study visit. Visit 1: Treatment C: Two (2) inhalations of Albuterol HFA (0.09 mg of albuterol sulfate per inhalation), for a total dosage of 0.18 mg; Visit 2: Treatment A: Two (2) inhalations of Primatene Mist (0.125 mg of epinephrine per inhalation), for a total dosage of 0.25 mg; Visit 3: Treatment B: Intramuscular injection of Epinephrine via Auto-Injector (0.30 mg of epinephrine solution in 0.30 mL), for a total dosage of 0.30 mg.
|
|---|---|---|---|
|
Treatment Period 1
STARTED
|
9
|
10
|
9
|
|
Treatment Period 1
COMPLETED
|
9
|
10
|
9
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
0
|
0
|
|
Washout Period 1 (2-7 Days)
STARTED
|
9
|
10
|
9
|
|
Washout Period 1 (2-7 Days)
COMPLETED
|
9
|
10
|
8
|
|
Washout Period 1 (2-7 Days)
NOT COMPLETED
|
0
|
0
|
1
|
|
Treatment Period 2
STARTED
|
9
|
10
|
8
|
|
Treatment Period 2
COMPLETED
|
9
|
10
|
8
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
0
|
0
|
|
Washout Period 2 (2-7 Days)
STARTED
|
9
|
10
|
8
|
|
Washout Period 2 (2-7 Days)
COMPLETED
|
9
|
10
|
7
|
|
Washout Period 2 (2-7 Days)
NOT COMPLETED
|
0
|
0
|
1
|
|
Treatment Period 3
STARTED
|
9
|
10
|
7
|
|
Treatment Period 3
COMPLETED
|
9
|
10
|
7
|
|
Treatment Period 3
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
A-B-C
Subjects received one of the three treatments during each study visit. Visit 1: Treatment A: Two (2) inhalations of Primatene Mist (0.125 mg of epinephrine per inhalation), for a total dosage of 0.25 mg; Visit 2: Treatment B: Intramuscular injection of Epinephrine via Auto-Injector (0.30 mg of epinephrine solution in 0.30 mL), for a total dosage of 0.30 mg; Visit 3: Treatment C: Two (2) inhalations of Albuterol HFA (0.09 mg of albuterol sulfate per inhalation), for a total dosage of 0.18 mg.
|
B-C-A
Subjects received one of the three treatments during each study visit. Visit 1: Treatment B: Intramuscular injection of Epinephrine via Auto-Injector (0.30 mg of epinephrine solution in 0.30 mL), for a total dosage of 0.30 mg; Visit 2: Treatment C: Two (2) inhalations of Albuterol HFA (0.09 mg of albuterol sulfate per inhalation), for a total dosage of 0.18 mg; Visit 3: Treatment A: Two (2) inhalations of Primatene Mist (0.125 mg of epinephrine per inhalation), for a total dosage of 0.25 mg.
|
C-A-B
Subjects received one of the three treatments during each study visit. Visit 1: Treatment C: Two (2) inhalations of Albuterol HFA (0.09 mg of albuterol sulfate per inhalation), for a total dosage of 0.18 mg; Visit 2: Treatment A: Two (2) inhalations of Primatene Mist (0.125 mg of epinephrine per inhalation), for a total dosage of 0.25 mg; Visit 3: Treatment B: Intramuscular injection of Epinephrine via Auto-Injector (0.30 mg of epinephrine solution in 0.30 mL), for a total dosage of 0.30 mg.
|
|---|---|---|---|
|
Washout Period 1 (2-7 Days)
Withdrawal by Subject
|
0
|
0
|
1
|
|
Washout Period 2 (2-7 Days)
Withdrawal by Subject
|
0
|
0
|
1
|
Baseline Characteristics
Study of Drug Exposure in Systemic Circulation of Primatene Mist by Oral Inhalation, Versus Epinephrine Injection by Intramuscular Injection and ProAir by Oral Inhalation in Healthy Individuals
Baseline characteristics by cohort
| Measure |
All Study Participants
n=28 Participants
All participants who have been randomized.
|
|---|---|
|
Age, Continuous
|
37.1 years
STANDARD_DEVIATION 7.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
13 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African-American
|
10 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Samples were drawn at 30 minutes pre-dose and at 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 25, 30, 40, 50, 60, 70, 80, 90, 120 minutes, 4, 6, 8, 12, 18, and 24 hours post-dose.Population: Per Protocol Population, defined as all subjects who have received all study medications and are evaluable for all treatments.
Pharmacokinetic (PK) blood samples will be collected starting 30 minutes before dose and until 24 hours after dose. Plasma will be isolated for analyzing the concentrations of Albuterol and Epinephrine. C\[max\] will be obtained directly from the plot of PK curve.
Outcome measures
| Measure |
Primatene Mist, E004
n=24 Participants
Participants who dosed with Primatene Mist.
Epinephrine (0.125 mg/inhalation): Participants will self-administer 2 inhalations of Epinephrine (0.125 mg/inhalation) for a total dosage of 0.25 mg.
|
Epinephrine Injection Auto-Injector (Generic of EpiPen)
n=24 Participants
Participants who were dosed with an Epinephrine Injection Auto-Injector.
Epinephrine Injection Auto-Injector (0.3mg/0.3mL): Participants will receive an intramuscular injection of Epinephrine via Auto-Injector (0.30 mg of epinephrine solution in 0.30 mL). The 0.30 mL dose will be given perpendicularly as a single deep intramuscular injection into the anterolateral aspect of the thigh.
|
Albuterol HFA
n=24 Participants
Participants who dosed with Albuterol HFA.
Albuterol Sulfate (0.09 mg/inhalation): Participants will self-administer 2 inhalations of Albuterol Sulfate (0.09 mg/inhalation) for a total dosage of 0.18 mg.
|
|---|---|---|---|
|
C[Max], Maximum Plasma Concentration of Albuterol or Epinephrine
|
240.8 pg/mL
Standard Deviation 2.4
|
704.8 pg/mL
Standard Deviation 1.8
|
599.8 pg/mL
Standard Deviation 1.7
|
PRIMARY outcome
Timeframe: Samples were drawn at 30 minutes pre-dose and at 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 25, 30, 40, 50, 60, 70, 80, 90, 120 minutes, 4, 6, 8, 12, 18, and 24 hours post-dose.Population: Per Protocol Population, defined as all subjects who have received all study medications and are evaluable for all treatments.
Pharmacokinetic (PK) blood samples will be collected starting 30 minutes before dose and until 24 hours after dose. Plasma will be isolated for analyzing the concentrations of Albuterol and Epinephrine. AUC(0-tm)\_TOT will be calculated with the trapezoid method. Time tm is defined as the time after C\[max\] is reached where API concentration is reduced to the levels of the same day baseline.
Outcome measures
| Measure |
Primatene Mist, E004
n=24 Participants
Participants who dosed with Primatene Mist.
Epinephrine (0.125 mg/inhalation): Participants will self-administer 2 inhalations of Epinephrine (0.125 mg/inhalation) for a total dosage of 0.25 mg.
|
Epinephrine Injection Auto-Injector (Generic of EpiPen)
n=24 Participants
Participants who were dosed with an Epinephrine Injection Auto-Injector.
Epinephrine Injection Auto-Injector (0.3mg/0.3mL): Participants will receive an intramuscular injection of Epinephrine via Auto-Injector (0.30 mg of epinephrine solution in 0.30 mL). The 0.30 mL dose will be given perpendicularly as a single deep intramuscular injection into the anterolateral aspect of the thigh.
|
Albuterol HFA
n=24 Participants
Participants who dosed with Albuterol HFA.
Albuterol Sulfate (0.09 mg/inhalation): Participants will self-administer 2 inhalations of Albuterol Sulfate (0.09 mg/inhalation) for a total dosage of 0.18 mg.
|
|---|---|---|---|
|
AUC(0-tm)_TOT, Area Under the Curve (AUC) of Total (Exogenous and Endogenous, if Available) Active Product Ingredient (API) From Time 0 to Time (tm)
|
26.8 pg/mL x hr
Standard Deviation 3.1
|
509.9 pg/mL x hr
Standard Deviation 1.5
|
3332.3 pg/mL x hr
Standard Deviation 1.3
|
PRIMARY outcome
Timeframe: Samples were drawn at 30 minutes pre-dose and at 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 25, 30, 40, 50, 60, 70, 80, 90, 120 minutes, 4, 6, 8, 12, 18, and 24 hours post-dose.Population: Per Protocol Population, defined as all subjects who have received all study medications and are evaluable for all treatments.
Pharmacokinetic (PK) blood samples will be collected starting 30 minutes before dose and until 24 hours after dose. Plasma will be isolated for analyzing the concentrations of Albuterol and Epinephrine. AUC(0-tm)\_DE will be calculated with the trapezoid method. Time tm is defined as the time after C\[max\] is reached where API concentration is reduced to the levels of the same day baseline.
Outcome measures
| Measure |
Primatene Mist, E004
n=24 Participants
Participants who dosed with Primatene Mist.
Epinephrine (0.125 mg/inhalation): Participants will self-administer 2 inhalations of Epinephrine (0.125 mg/inhalation) for a total dosage of 0.25 mg.
|
Epinephrine Injection Auto-Injector (Generic of EpiPen)
n=24 Participants
Participants who were dosed with an Epinephrine Injection Auto-Injector.
Epinephrine Injection Auto-Injector (0.3mg/0.3mL): Participants will receive an intramuscular injection of Epinephrine via Auto-Injector (0.30 mg of epinephrine solution in 0.30 mL). The 0.30 mL dose will be given perpendicularly as a single deep intramuscular injection into the anterolateral aspect of the thigh.
|
Albuterol HFA
n=24 Participants
Participants who dosed with Albuterol HFA.
Albuterol Sulfate (0.09 mg/inhalation): Participants will self-administer 2 inhalations of Albuterol Sulfate (0.09 mg/inhalation) for a total dosage of 0.18 mg.
|
|---|---|---|---|
|
AUC(0-tm)_DE, Area Under the Curve (AUC) of Exogenous Active Product Ingredient (API) From Time 0 to Time (tm)
|
18.4 pg/mL x hr
Standard Deviation 3.6
|
396.3 pg/mL x hr
Standard Deviation 1.6
|
3332.3 pg/mL x hr
Standard Deviation 1.3
|
PRIMARY outcome
Timeframe: Samples were drawn at 30 minutes pre-dose and at 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 25, 30, 40, 50, 60, 70, 80, 90, 120 minutes, 4, 6, 8, 12, 18, and 24 hours post-dose.Population: Per Protocol Population, defined as all subjects who have received all study medications and are evaluable for all treatments.
Pharmacokinetic (PK) blood samples will be collected starting 30 minutes before dose and until 24 hours after dose. Plasma will be isolated for analyzing the concentrations of Albuterol and Epinephrine. AUC(0-inf) will be calculated with the extrapolation method.
Outcome measures
| Measure |
Primatene Mist, E004
n=24 Participants
Participants who dosed with Primatene Mist.
Epinephrine (0.125 mg/inhalation): Participants will self-administer 2 inhalations of Epinephrine (0.125 mg/inhalation) for a total dosage of 0.25 mg.
|
Epinephrine Injection Auto-Injector (Generic of EpiPen)
n=24 Participants
Participants who were dosed with an Epinephrine Injection Auto-Injector.
Epinephrine Injection Auto-Injector (0.3mg/0.3mL): Participants will receive an intramuscular injection of Epinephrine via Auto-Injector (0.30 mg of epinephrine solution in 0.30 mL). The 0.30 mL dose will be given perpendicularly as a single deep intramuscular injection into the anterolateral aspect of the thigh.
|
Albuterol HFA
n=24 Participants
Participants who dosed with Albuterol HFA.
Albuterol Sulfate (0.09 mg/inhalation): Participants will self-administer 2 inhalations of Albuterol Sulfate (0.09 mg/inhalation) for a total dosage of 0.18 mg.
|
|---|---|---|---|
|
AUC(0-inf), Area Under the Curve (AUC) of Albuterol or Epinephrine From Time 0 to Infinity
|
18.4 pg/mL x hr
Standard Deviation 3.6
|
411.4 pg/mL x hr
Standard Deviation 1.7
|
3650.4 pg/mL x hr
Standard Deviation 1.3
|
SECONDARY outcome
Timeframe: Samples were drawn at 30 minutes pre-dose and at 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 25, 30, 40, 50, 60, 70, 80, 90, 120 minutes, 4, 6, 8, 12, 18, and 24 hours post-dose.Population: Per Protocol Population, defined as all subjects who have received all study medications and are evaluable for all treatments.
Pharmacokinetic (PK) blood samples will be collected starting 30 minutes before dose and until 24 hours after dose. Plasma will be isolated for analyzing the concentrations of Albuterol and Epinephrine. t\[max\] will be obtained directly from the plot of PK curve when the maximum concentration is observed.
Outcome measures
| Measure |
Primatene Mist, E004
n=24 Participants
Participants who dosed with Primatene Mist.
Epinephrine (0.125 mg/inhalation): Participants will self-administer 2 inhalations of Epinephrine (0.125 mg/inhalation) for a total dosage of 0.25 mg.
|
Epinephrine Injection Auto-Injector (Generic of EpiPen)
n=24 Participants
Participants who were dosed with an Epinephrine Injection Auto-Injector.
Epinephrine Injection Auto-Injector (0.3mg/0.3mL): Participants will receive an intramuscular injection of Epinephrine via Auto-Injector (0.30 mg of epinephrine solution in 0.30 mL). The 0.30 mL dose will be given perpendicularly as a single deep intramuscular injection into the anterolateral aspect of the thigh.
|
Albuterol HFA
n=24 Participants
Participants who dosed with Albuterol HFA.
Albuterol Sulfate (0.09 mg/inhalation): Participants will self-administer 2 inhalations of Albuterol Sulfate (0.09 mg/inhalation) for a total dosage of 0.18 mg.
|
|---|---|---|---|
|
t[Max], Time at Which Maximum Plasma Concentration of Albuterol or Epinephrine is Observed
|
2.6 min
Standard Deviation 3.0
|
8.3 min
Standard Deviation 2.7
|
21.8 min
Standard Deviation 3.1
|
SECONDARY outcome
Timeframe: Samples were drawn at 30 minutes pre-dose and at 1, 2, 3, 5, 7, 9, 12, 15, 18, 21, 25, 30, 40, 50, 60, 70, 80, 90, 120 minutes, 4, 6, 8, 12, 18, and 24 hours post-dose.Population: Per Protocol Population, defined as all subjects who have received all study medications and are evaluable for all treatments.
Pharmacokinetic (PK) blood samples will be collected starting 30 minutes before dose and until 24 hours after dose. Plasma will be isolated for analyzing the concentrations of Albuterol and Epinephrine.
Outcome measures
| Measure |
Primatene Mist, E004
n=24 Participants
Participants who dosed with Primatene Mist.
Epinephrine (0.125 mg/inhalation): Participants will self-administer 2 inhalations of Epinephrine (0.125 mg/inhalation) for a total dosage of 0.25 mg.
|
Epinephrine Injection Auto-Injector (Generic of EpiPen)
n=24 Participants
Participants who were dosed with an Epinephrine Injection Auto-Injector.
Epinephrine Injection Auto-Injector (0.3mg/0.3mL): Participants will receive an intramuscular injection of Epinephrine via Auto-Injector (0.30 mg of epinephrine solution in 0.30 mL). The 0.30 mL dose will be given perpendicularly as a single deep intramuscular injection into the anterolateral aspect of the thigh.
|
Albuterol HFA
n=24 Participants
Participants who dosed with Albuterol HFA.
Albuterol Sulfate (0.09 mg/inhalation): Participants will self-administer 2 inhalations of Albuterol Sulfate (0.09 mg/inhalation) for a total dosage of 0.18 mg.
|
|---|---|---|---|
|
t[1/2], Terminal Elimination Half-life of Albuterol or Epinephrine
|
7.1 min
Standard Deviation 5.2
|
138.8 min
Standard Deviation 4.0
|
420.7 min
Standard Deviation 1.2
|
Adverse Events
Primatene Mist, E004
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Epinephrine Injection Auto-Injector (Generic of EpiPen)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Albuterol HFA
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Primatene Mist, E004
n=27 participants at risk
Participants who dosed with Primatene Mist.
Epinephrine (0.125 mg/inhalation): Participants will self-administer 2 inhalations of Epinephrine (0.125 mg/inhalation) for a total dosage of 0.25 mg.
|
Epinephrine Injection Auto-Injector (Generic of EpiPen)
n=26 participants at risk
Participants who were dosed with an Epinephrine Injection Auto-Injector.
Epinephrine Injection Auto-Injector (0.3mg/0.3mL): Participants will receive an intramuscular injection of Epinephrine via Auto-Injector (0.30 mg of epinephrine solution in 0.30 mL). The 0.30 mL dose will be given perpendicularly as a single deep intramuscular injection into the anterolateral aspect of the thigh.
|
Albuterol HFA
n=28 participants at risk
Participants who dosed with Albuterol HFA.
Albuterol Sulfate (0.09 mg/inhalation): Participants will self-administer 2 inhalations of Albuterol Sulfate (0.09 mg/inhalation) for a total dosage of 0.18 mg.
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/27 • From signing of consent until follow-up (approximately 4 weeks)
|
0.00%
0/26 • From signing of consent until follow-up (approximately 4 weeks)
|
3.6%
1/28 • Number of events 1 • From signing of consent until follow-up (approximately 4 weeks)
|
|
General disorders
Injection Site Pain
|
0.00%
0/27 • From signing of consent until follow-up (approximately 4 weeks)
|
3.8%
1/26 • Number of events 1 • From signing of consent until follow-up (approximately 4 weeks)
|
0.00%
0/28 • From signing of consent until follow-up (approximately 4 weeks)
|
|
Nervous system disorders
Headache
|
11.1%
3/27 • Number of events 3 • From signing of consent until follow-up (approximately 4 weeks)
|
0.00%
0/26 • From signing of consent until follow-up (approximately 4 weeks)
|
3.6%
1/28 • Number of events 1 • From signing of consent until follow-up (approximately 4 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis
|
3.7%
1/27 • Number of events 1 • From signing of consent until follow-up (approximately 4 weeks)
|
0.00%
0/26 • From signing of consent until follow-up (approximately 4 weeks)
|
0.00%
0/28 • From signing of consent until follow-up (approximately 4 weeks)
|
Additional Information
Amphastar Pharmaceuticals, Inc.
Amphastar Pharmaceuticals, Inc.
Phone: (909) 980-9484
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place