search
Back to results

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

Primary Purpose

Pharmacokinetics, Epinephrine, Albuterol

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Epinephrine (0.125 mg/inhalation)
Epinephrine Injection Auto-Injector (0.3mg/0.3mL)
Albuterol Sulfate (0.09 mg/inhalation)
Sponsored by
Amphastar Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pharmacokinetics

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Agree to participate; understand and sign informed consent;
  • Male and female adults, aged 18 to 50 years, inclusive at Screening;
  • Generally healthy and medically stable, with no clinically significant abnormalities based on physical examination and laboratory tests as determined by the Investigators;
  • Have good venous access;
  • Have normal resting blood pressure and normal heart rate (HR) without history of syncope; a subject with out of range blood pressure may be enrolled in the study at the discretion of the Principal Investigator;
  • Have a body mass index (BMI) of 18.0 - 30.0 kg/m^2;
  • Female candidates must be >1 year post-menopausal or practicing a clinically acceptable form of birth control and confirmed by negative urine or serum pregnancy test at Screening;
  • Negative HIV-Ab, HBs-Ag and HCV-Ab;
  • Negative alcohol test (urine or breathalyzer);
  • Negative drug screening results;
  • Currently non-smoker; have not used any tobacco products for at least three (3) months prior to Screening; and
  • Demonstrate proficiency in the use of MDI and a consistent inhalation time >2.0 seconds after training, for at least three (3) times, with a maximum of 5 attempts.

Exclusion Criteria:

  • Concurrent clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine, psychiatric, or malignant diseases.
  • Known intolerance or hypersensitivity to any component of the study drugs (i.e., Epinephrine, Albuterol Sulfate or any sympathomimetic drugs, HFA-134a, thymol, ethanol, ascorbic acid, nitric acid, and hydrochloric acid).
  • Upper or lower respiratory tract infection, or other systemic infection within 6 weeks prior to Screening;
  • Clinically significant abnormalities in the screening/baseline ECG; prolonged corrected QT interval (QTcF) on ECG: men >450ms, women: >470ms; single or multiple premature ventricular contractions (PVC);
  • Abnormal thyroid function test (if TSH is out of range, refer to T3/T4 for thyroid function assessment);
  • Subject has been on other investigational drug/device studies within 30 days of Screening Visit or planned participation in another investigational drug trial at any time during this trial;
  • Women who are pregnant or lactating or planning a pregnancy during the study period;
  • Subject has donated or lost > 500 mL of blood within 3 months of Screening;
  • Evidence of alcohol or drug abuse or dependency within 6 months prior to screening; or
  • Use of any of the prohibited drugs without appropriate washout.

Sites / Locations

  • Amphastar Study Site 0035

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

Primatene Mist, E004

Epinephrine Injection Auto-Injector (Generic of EpiPen)

Albuterol HFA

Arm Description

Participants who dosed with Primatene Mist.

Participants who were dosed with an Epinephrine Injection Auto-Injector.

Participants who dosed with Albuterol HFA.

Outcomes

Primary Outcome Measures

C[Max], Maximum Plasma Concentration of Albuterol or Epinephrine
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.
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)
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.
AUC(0-tm)_DE, Area Under the Curve (AUC) of Exogenous Active Product Ingredient (API) From Time 0 to Time (tm)
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.
AUC(0-inf), Area Under the Curve (AUC) of Albuterol or Epinephrine From Time 0 to Infinity
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.

Secondary Outcome Measures

t[Max], Time at Which Maximum Plasma Concentration of Albuterol or Epinephrine is Observed
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.
t[1/2], Terminal Elimination Half-life of Albuterol or Epinephrine
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.

Full Information

First Posted
December 19, 2019
Last Updated
March 4, 2021
Sponsor
Amphastar Pharmaceuticals, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT04207840
Brief Title
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
Official Title
Study of Drug Exposure in Systemic Circulation of Primatene Mist (0.25mg) by Oral Inhalation, Versus Epinephrine Injection (0.30mg) by Intramuscular Injection and ProAir (0.18mg) by Oral Inhalation in Healthy Individuals: A Randomized, Safety Evaluator-blind, Three-Treatment, Crossover, Fasting Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
December 9, 2019 (Actual)
Primary Completion Date
December 20, 2019 (Actual)
Study Completion Date
December 23, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amphastar Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
To assess the drug exposure profile in systemic circulation of Primatene Mist by inhalation, versus Epinephrine by intramuscular injection, and ProAir HFA by inhalation in healthy adults.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pharmacokinetics, Epinephrine, Albuterol, Asthma, Anaphylaxis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Primatene Mist, E004
Arm Type
Experimental
Arm Description
Participants who dosed with Primatene Mist.
Arm Title
Epinephrine Injection Auto-Injector (Generic of EpiPen)
Arm Type
Active Comparator
Arm Description
Participants who were dosed with an Epinephrine Injection Auto-Injector.
Arm Title
Albuterol HFA
Arm Type
Active Comparator
Arm Description
Participants who dosed with Albuterol HFA.
Intervention Type
Combination Product
Intervention Name(s)
Epinephrine (0.125 mg/inhalation)
Other Intervention Name(s)
Primatene Mist
Intervention Description
Participants will self-administer 2 inhalations of Epinephrine (0.125 mg/inhalation) for a total dosage of 0.25 mg.
Intervention Type
Combination Product
Intervention Name(s)
Epinephrine Injection Auto-Injector (0.3mg/0.3mL)
Other Intervention Name(s)
Generic of EpiPen
Intervention Description
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.
Intervention Type
Combination Product
Intervention Name(s)
Albuterol Sulfate (0.09 mg/inhalation)
Other Intervention Name(s)
Albuterol HFA
Intervention Description
Participants will self-administer 2 inhalations of Albuterol Sulfate (0.09 mg/inhalation) for a total dosage of 0.18 mg.
Primary Outcome Measure Information:
Title
C[Max], Maximum Plasma Concentration of Albuterol or Epinephrine
Description
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.
Time Frame
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.
Title
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)
Description
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.
Time Frame
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.
Title
AUC(0-tm)_DE, Area Under the Curve (AUC) of Exogenous Active Product Ingredient (API) From Time 0 to Time (tm)
Description
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.
Time Frame
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.
Title
AUC(0-inf), Area Under the Curve (AUC) of Albuterol or Epinephrine From Time 0 to Infinity
Description
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.
Time Frame
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.
Secondary Outcome Measure Information:
Title
t[Max], Time at Which Maximum Plasma Concentration of Albuterol or Epinephrine is Observed
Description
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.
Time Frame
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.
Title
t[1/2], Terminal Elimination Half-life of Albuterol or Epinephrine
Description
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.
Time Frame
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Agree to participate; understand and sign informed consent; Male and female adults, aged 18 to 50 years, inclusive at Screening; Generally healthy and medically stable, with no clinically significant abnormalities based on physical examination and laboratory tests as determined by the Investigators; Have good venous access; Have normal resting blood pressure and normal heart rate (HR) without history of syncope; a subject with out of range blood pressure may be enrolled in the study at the discretion of the Principal Investigator; Have a body mass index (BMI) of 18.0 - 30.0 kg/m^2; Female candidates must be >1 year post-menopausal or practicing a clinically acceptable form of birth control and confirmed by negative urine or serum pregnancy test at Screening; Negative HIV-Ab, HBs-Ag and HCV-Ab; Negative alcohol test (urine or breathalyzer); Negative drug screening results; Currently non-smoker; have not used any tobacco products for at least three (3) months prior to Screening; and Demonstrate proficiency in the use of MDI and a consistent inhalation time >2.0 seconds after training, for at least three (3) times, with a maximum of 5 attempts. Exclusion Criteria: Concurrent clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine, psychiatric, or malignant diseases. Known intolerance or hypersensitivity to any component of the study drugs (i.e., Epinephrine, Albuterol Sulfate or any sympathomimetic drugs, HFA-134a, thymol, ethanol, ascorbic acid, nitric acid, and hydrochloric acid). Upper or lower respiratory tract infection, or other systemic infection within 6 weeks prior to Screening; Clinically significant abnormalities in the screening/baseline ECG; prolonged corrected QT interval (QTcF) on ECG: men >450ms, women: >470ms; single or multiple premature ventricular contractions (PVC); Abnormal thyroid function test (if TSH is out of range, refer to T3/T4 for thyroid function assessment); Subject has been on other investigational drug/device studies within 30 days of Screening Visit or planned participation in another investigational drug trial at any time during this trial; Women who are pregnant or lactating or planning a pregnancy during the study period; Subject has donated or lost > 500 mL of blood within 3 months of Screening; Evidence of alcohol or drug abuse or dependency within 6 months prior to screening; or Use of any of the prohibited drugs without appropriate washout.
Facility Information:
Facility Name
Amphastar Study Site 0035
City
Cypress
State/Province
California
ZIP/Postal Code
90630
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
Access to patient level data and supporting clinical documents may be requested by qualified researchers. Requests will be reviewed on the basis of scientific merit. Patient data will be de-identified to protect the privacy of trial patients in line with applicable laws and regulations.

Learn more about this trial

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

We'll reach out to this number within 24 hrs