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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04207840
Recruitment Status : Completed
First Posted : December 23, 2019
Last Update Posted : July 8, 2020
Sponsor:
Information provided by (Responsible Party):
Amphastar Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE December 19, 2019
First Posted Date  ICMJE December 23, 2019
Last Update Posted Date July 8, 2020
Actual Study Start Date  ICMJE December 9, 2019
Actual Primary Completion Date December 20, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 19, 2019)
  • Area Under the Curve (AUC) of Epinephrine Plasma Concentration from time 0 to 6 hours post-dose, AUC[0-6h] [ Time Frame: From 30 minutes before dose until 24 hours after dose ]
    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[0-6h] will be calculated with the trapezoid method.
  • Area Under the Curve (AUC) of Albuterol Plasma Concentration from time 0 to 24 hours post-dose, AUC[0-24h] [ Time Frame: From 30 minutes before dose until 24 hours after dose ]
    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[0-24h] will be calculated with the trapezoid method.
  • Area Under the Curve (AUC) of Albuterol or Epinephrine Plasma Concentration from time 0 to infinity, AUC[0-inf] [ Time Frame: From 30 minutes before dose until 24 hours after dose ]
    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.
  • Maximum Plasma Concentration of Albuterol or Epinephrine, C[max] [ Time Frame: From 30 minutes before dose until 24 hours after dose ]
    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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2019)
  • Time at which Maximum Plasma Concentration of Albuterol or Epinephrine is observed, t[max] [ Time Frame: From 30 minutes before dose until 24 hours after dose ]
    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.
  • Terminal Elimination Half-life of Albuterol or Epinephrine, T[1/2] [ Time Frame: From 30 minutes before dose until 24 hours after dose ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Pharmacokinetics
  • Epinephrine
  • Albuterol
  • Asthma
  • Anaphylaxis
Intervention  ICMJE
  • Combination Product: 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.
    Other Name: Primatene Mist
  • Combination Product: 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.
    Other Name: Generic of EpiPen
  • Combination Product: 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.
    Other Name: Albuterol HFA
Study Arms  ICMJE
  • Experimental: Primatene Mist, E004
    Participants who dosed with Primatene Mist.
    Intervention: Combination Product: Epinephrine (0.125 mg/inhalation)
  • Active Comparator: Epinephrine Injection Auto-Injector (Generic of EpiPen)
    Participants who were dosed with an Epinephrine Injection Auto-Injector.
    Intervention: Combination Product: Epinephrine Injection Auto-Injector (0.3mg/0.3mL)
  • Active Comparator: Albuterol HFA
    Participants who dosed with Albuterol HFA.
    Intervention: Combination Product: Albuterol Sulfate (0.09 mg/inhalation)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 19, 2019)
28
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 23, 2019
Actual Primary Completion Date December 20, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04207840
Other Study ID Numbers  ICMJE API-E004-CL-I
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
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.
Responsible Party Amphastar Pharmaceuticals, Inc.
Study Sponsor  ICMJE Amphastar Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Amphastar Pharmaceuticals, Inc.
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP