Epinephrine Inhalation Aerosol USP, CLINICAL STUDY-B3 FOR ASSESSMENT OF PHARMACOKINETICS

This study has been completed.
Sponsor:
Information provided by:
Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01255709
First received: December 3, 2010
Last updated: January 27, 2011
Last verified: January 2011
  Purpose

This study examines the pharmacokinetic profile of Armstrong's proposed Epinephrine Inhalation Aerosol USP, an HFA134a propelled Metered Dose Inhaler (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.


Condition Intervention Phase
Asthma
Drug: Treatment arm T1
Drug: Treatment arm T2
Drug: Treatment arm C
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: CLINICAL STUDY-B3 FOR ASSESSMENT OF PHARMACOKINETICS, A Randomized, Evaluator-Blind, Single-Dose, Three Arm, Crossover,PK Study in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by Amphastar Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Pharmacokinetics including maximum concentration and area under the curve [ Time Frame: -30, 2, 5, 7.5, 10, 12.5, 15, 20, 25, 30, 45, 60, 90, 120, 240 and 360 min postdose. ] [ Designated as safety issue: No ]

    Samples will be analyzed with an established LC/MS/MS method, with a quantitative detection limit of 0.02 ng/mL, for both epinephrine-d3 and epinephrine-h3.

    • Mean Maximum concentration of epinephrine (Cmax for epinephrine)
    • Mean Area Under the Curve (AUC) for epinephrine
    • Time to maximum concentration (tmax) and Half life of the drug (t1/2)
    • Epinephrine concentrations versus time


Secondary Outcome Measures:
  • Vital Signs [ Time Frame: within 30 min predose, at 30, 60 and 360 min postdose ] [ Designated as safety issue: Yes ]
    Systolic and Diastolic Blood pressure and heart rate

  • 12-lead Electrocardiogram (ECG) [ Time Frame: within 30 min pre-dose, and at 15 and 120 min post-dose ] [ Designated as safety issue: Yes ]
    12 lead ECG (Routine and QT/QTc intervals)

  • Telemetry ECG [ Time Frame: within 30 min pre-dose, and during the initial 5 min post-dose ] [ Designated as safety issue: Yes ]
    Telemetry recording of heart rate


Enrollment: 24
Study Start Date: December 2010
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment arm T1
epinephrine inhalation aerosol, 90 mcg/inhalation, 12 inhalations over 6 minutes
Drug: Treatment arm T1
epinephrine inhalation aerosol, 90 mcg/inhalation, 12 inhalations over 6 minutes
Other Name: Primatene Mist HFA
Active Comparator: Treatment arm C
epinephrine inhalation aerosol, 220 mcg/inhalation, 12 inhalations over 6 minutes
Drug: Treatment arm C
epinephrine inhalation aerosol, 220 mcg/inhalation, 12 inhalations over 6 minutes
Other Name: Primatene Mist (epinephrine inhalation aerosol, USP)
Experimental: Treatment arm T2
epinephrine inhalation aerosol, 100 mcg/inhalation, 12 inhalations over 6 minutes
Drug: Treatment arm T2
epinephrine inhalation aerosol, 100 mcg/inhalation, 12 inhalations over 6 minutes
Other Name: Primatene Mist HFA

Detailed Description:

The current study is designed to complement and expand the previous PK studies, API-E004-CL-B and API-E004-CL-B2, with emphasis on lower E004 dose strengths (at 90 and 100 mcg per inhalation), for a more thorough evaluation of the E004 PK profiles. Safety of E004 will also be evaluated, under augmented dose conditions.

  Eligibility

Ages Eligible for Study:   18 Years to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Generally healthy at screening;
  • Body weight ≥ 50 kg for men and ≥ 45 kg for women;
  • Sitting blood pressure ≤ 135/90 mmHg;
  • Demonstrating negative hIV, HBsAG and DCV-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 prior to Screening;
  • 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 drug/device studies, or donated blood, in the last 30 days prior to Screening;
  • Other criteria apply
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01255709

Locations
United States, California
Amphastar Study Site 1
Cypress, California, United States, 90630
Sponsors and Collaborators
Amphastar Pharmaceuticals, Inc.
Investigators
Study Director: Medical Director Amphastar Pharmaceuticals, Inc.
  More Information

Publications:
Responsible Party: Medical Director, Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01255709     History of Changes
Other Study ID Numbers: API-E004-CL-B3
Study First Received: December 3, 2010
Last Updated: January 27, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Amphastar Pharmaceuticals, Inc.:
Asthma
shortness of breath
wheezing

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Epinephrine
Epinephryl borate
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Mydriatics
Adrenergic alpha-Agonists
Sympathomimetics
Vasoconstrictor Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on April 17, 2014