Epinephrine Inhalation Aerosol USP, a HFA-MDI Study for Assessment of Pharmacokinetics

NCT ID: NCT01188577

Last Updated: 2017-07-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2011-01-31

Brief Summary

This study examines the pharmacokinetic profile of Armstrong's proposed Epinephrine Inhalation Aerosol USP, an HFA-MDI (E004), using a stable isotope deuterium-labeled epinephrine (epinephrine-d3) to differentiate the administered drug from the endogenous epinephrine, in healthy male and female adult volunteers. The current study is designed for a more thorough evaluation of the E004 Pharmacokinetics. Safety of E004 will also be evaluated, under augmented dose conditions.

Detailed Description

E004 is formulated with epinephrine free base as the active ingredient, and hydrofluoroalkane (HFA-134a) as the propellant.

In order to differentiate the inhaled epinephrine from the fluctuating background of endogenous epinephrine 1, a stable-isotope deuterium (2H) labeled epinephrine (epinephrine-d3) preparation will be used to formulate E004 inhalers, denoted as E004-d3. PK of E004 at 125 mcg of epinephrine-d3 per inhalation, will be compared to that of the currently marketed, non-labeled, Epinephrine-CFC MDI as the Reference Control (220 mcg per inhalation).

This study is a randomized, evaluator-blind, single dose, two-arm, crossover, PK study, to be conducted in ~18 healthy, male and female, adult volunteers. PK will be studied using E004-d3 at 125 mcg per inhalation (Arm T). A currently marketed, non-labeled, Epinephrine CFC-MDI will be used as a Reference Control (Arm C).

Conditions

Asthma; Bronchospasm; Wheezing; Shortness of Breath

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Epinephrine Inhalation Aerosol, HFA

Experimental treatment of 10 inhalations of 125 mcg epinephrine base propelled by HFA 134a

Group Type: EXPERIMENTAL

Epinephrine Inhalation Aerosol, HFA

Intervention Type: DRUG

10 inhalations of epinephrine inhalation aerosol, 125 mcg/inhalation

Epinephrine Inhalation Aerosol, CFC

Epinephrine Inhalation Aerosol, CFC propelled, 220 mcg/inhalation , 10 inhalations

Group Type: ACTIVE_COMPARATOR

Epinephrine Inhalation Aerosol

Intervention Type: DRUG

Epinephrine Inhalation Aerosol, 220 mcg/ inhalation, 10 inhalations

Interventions

Epinephrine Inhalation Aerosol, HFA

10 inhalations of epinephrine inhalation aerosol, 125 mcg/inhalation

Intervention Type: DRUG

Epinephrine Inhalation Aerosol

Epinephrine Inhalation Aerosol, 220 mcg/ inhalation, 10 inhalations

Intervention Type: DRUG

Other Intervention Names

HFA epinephrine inhalation aerosol, 125 mcg/inhalation; Primatene Mist; Epinephrine Inhalation Aerosol, USP

Eligibility Criteria

Inclusion Criteria

• Generally healthy at screening;
• No clinically significant respiratory, cardiovascular and other systemic or organic illnesses;
• Body weight ≥ 50 kg for men and ≥ 45 kg for women,
• Sitting blood pressure ≤ 135/90 mm Hg;
• Demonstrating negative HIV, HBsAg and HCV-Ab screen tests;
• Women of child-bearing potential must be non-pregnant, non-lactating, and practicing a clinically acceptable form of birth control;
• Properly consented
• Other criteria apply

Exclusion Criteria

• A smoking history of ≥10 pack-years, or having smoked within 6 months;
• Upper respiratory tract infections within 2 wk, or lower respiratory tract infection within 4 wk, prior to Screening;
• Any current or recent respiratory conditions that might significantly affect pharmacodynamic response to the study drugs;
• Known intolerance or hypersensitivity to the study MDI ingredients;
• Having been on other investigational studies, or donated blood, in the last 30 days;
• Other Criteria Apply

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Amphastar Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Amphastar Pharmaceuticals, Inc.

Locations

Amphastar Site 0035

Cypress, California, United States

Countries

United States

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Kerwin EM, Marrs T, Luo MZ, Zhang JY. Pharmacokinetic Study of Epinephrine Hydrofluoroalkane (Primatene MIST) Metered-Dose Inhaler. J Aerosol Med Pulm Drug Deliv. 2020 Oct;33(5):282-287. doi: 10.1089/jamp.2019.1577. Epub 2020 May 18.

Reference Type: DERIVED

PMID: 32423275 (View on PubMed)

Other Identifiers

API-E004-CL-B2

Identifier Type: -

Identifier Source: org_study_id