Randomized, Placebo/Active Crossover Dose-ranging Study for Safety and Efficacy in Asthma Patients.

May 14, 2018 updated by: Amphastar Pharmaceuticals, Inc.

A Randomized, Double-blinded or Evaluator-blinded, Placebo and Active Controlled, Six-arm, Crossover, Single Dose, Dose-ranging Study, for Initial Evaluation of Safety and Efficacy in Asthma Patients

The main objective of this study is to evaluate the efficacy and safety of the Armstrong's Epinephrine HFA-MDI (E004) formulation, in comparison to the Placebo (Placebo-HFA) and an Active Control (Epinephrine CFC-MDI), and to identify the optimum E004 dose strength(s) for the ensuing pivotal clinical trials. The study will be conducted in adult patients who have intermittent, or mild-to-moderate persistent, asthma, but are otherwise healthy.

The bronchodilatory efficacy of E004, is evaluated in terms of post-dose area under the curves (AUC) of FEV1 changes (% and volumes), from the pre-dose baseline values, in comparison to the Placebo Control and the Active Control.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Jose, California, United States, 95117
        • Amphastar Site 0001
      • Stockton, California, United States, 95207
        • Amphastar Site 0003

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Generally healthy, male and female adults aged 18 to 55 years at Screening.
  2. Clinical diagnosis of intermittent, or mild-to-moderate persistent, asthma for at least 6 months before Screening, and having used inhaled epinephrine or β-agonist(s) for asthma control;
  3. Demonstrating a baseline forced expiratory volume in 1 second (FEV1) at 50-90 percent of predicted normal at Screening;
  4. Demonstrating a 12.0 percent or greater airway reversibility in FEV1 within 30 min after inhaling 2 actuations of Epinephrine CFC-MDI (440 mcg Epinephrine base) at Screening;
  5. Females of child-bearing potential must be non-pregnant, non-lactating, and practicing a clinically acceptable form of birth control;
  6. Demonstration of proficiency in the use of a MDI inhaler after training;
  7. Having properly consented to participate in the trial.

Exclusion Criteria:

  1. A smoking history of 10 or more pack-years, or having smoked within 6 months prior to Screening;
  2. Upper respiratory tract infections within 2 wk, or lower respiratory tract infection within 4 wk, prior to Screening;
  3. Asthma exacerbations that required emergency care or hospitalized treatment, within 4 wk prior to Screening;
  4. Any current or recent respiratory conditions that, per investigator discretion, might significantly affect pharmacodynamic response to the study drugs, including cystic fibrosis, bronchiectasis, tuberculosis, emphysema, and other significant respiratory diseases besides asthma;
  5. Concurrent clinically significant cardiovascular, hematological, renal, neurologic, hepatic, endocrine (including diabetes), psychiatric, neoplastic or other illnesses that in the opinion of the investigator could impact on the conduct, safety and evaluation of the study;
  6. Known intolerance or hypersensitivity to any of the study MDI ingredients (i.e., Epinephrine, HFA-134a, CFC-12, CFC-114, polysorbate-80, ethanol, thymol, nitric acid and ascorbic acid);
  7. Use of prohibited drugs or failure to observe the drug washout restrictions;
  8. Having been on other investigational drug/device studies in the last 30 days prior to Screening.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: T1 - E004 90 mcg/actuation
T1 - E004 (epinephrine inhalation aerosol) 90 mcg/actuation - treatment by 2 actuations of E004 at 90 mcg/actuation
Drug: E004 (epinephrine inhalation aerosol), 90 mcg/actuation
E004 (epinephrine inhalation aerosol), 90 mcg/actuation, 2 actuations, single dose crossover, 1 -14 day washout period
Other Names:
  • Primatene Mist HFA
EXPERIMENTAL: T2 - E004 125 mcg/actuation
E004 (epinephrine inhalation aerosol), 125 mcg, 2 actuations
Drug: E004 (epinephrine inhalation aerosol), 125 mcg
E004 (epinephrine inhalation aerosol), 125 mcg/actuation, 2 actuations, single dose crossover, 1 - 14 day washout period
Other Names:
  • Primatene Mist HFA
EXPERIMENTAL: T3 - 160 mcg/actuation
E004 (epinephrine inhalation aerosol), 160 mcg - E004 (epinephrine inhalation aerosol), 160 mcg/ actuation, 2 actuations
Drug: E004 (epinephrine inhalation aerosol), 160 mcg
E004 (epinephrine inhalation aerosol), 160 mcg/actuation, 2 actuations, single dose crossover, 1 - 14 days washout period
Other Names:
  • Primatene Mist HFA
EXPERIMENTAL: T4 - 220 mcg/actuation
E004 (epinephrine inhalation aerosol), 220 mcg - 220 mcg/actuation, 2 actuations
Drug: E004 (epinephrine inhalation aerosol), 220 mcg
E004 (epinephrine inhalation aerosol), 220 mcg - 220 mcg/actuation, 2 actuations, single dose crossover, 1 - 14 days washout period
Other Names:
  • Primatene Mist HFA
ACTIVE_COMPARATOR: A - Active control
epinephrine inhalation aerosol, CFC propelled 220 mcg Epinephrine Inhalation Aerosol, CFC-MDI, 2 actuations
Drug: epinephrine inhalation aerosol, CFC propelled
epinephrine inhalation aerosol, 220 mcg/actuation, 2 actuations, single dose crossover, 1 - 14 day washout period
Other Names:
  • Primatene Mist
PLACEBO_COMPARATOR: P, Placebo HFA
E004 placebo single treatment with 2 inhalations
Drug: E004 Placebo
E004 Placebo, 0 mcg epinephrine inhalation aerosol, 2 actuations, 1 -14 day washout period

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The AUC of post-dose FEV1 percentage changes (Δ%) from the Pre-dose baseline. The primary analysis of the primary endpoint is the difference of Δ% FEV1, compared between the E004 treatment arms (T1, T2, T3 and T4) and the Placebo control (Arm P).
Time Frame: 360 minutes post-dose
360 minutes post-dose

Secondary Outcome Measures

Outcome Measure
Time Frame
Dose response relationship of Epinephrine HFA-MDI, analyzed using efficacy data from all E004 doses.
Time Frame: 360 minutes post dose
360 minutes post dose
AUC of FEV1 volume post-dose changes (Δ Volume) from the Pre-dose baseline.
Time Frame: 360 minutes post dose
360 minutes post dose
Time to onset of bronchodilator effect, determined by linear interpolation as the point where FEV1 first reaches 12.0 percent from the Pre-dose Baseline.
Time Frame: 30 (±5) min post-dose
30 (±5) min post-dose
The peak bronchodilator response (Fmax), defined as the maximum post-dose FEV1 percent change.
Time Frame: 360 minutes post dose
360 minutes post dose
The time to peak FEV1 effect (Tmax), defined as the time of Fmax.
Time Frame: 360 minutes post dose
360 minutes post dose
Duration of effect, calculated as the total duration of bronchodilator effects when post-dose FEV1 reaches and stays 12.0 percent above the Pre-dose Baseline.
Time Frame: 360 minutes post dose
360 minutes post dose
Response Rate of responders who demonstrate 12.0 percent or greater FEV1 changes from the Pre-dose baseline.
Time Frame: 360 minutes post dose
360 minutes post dose
Vital signs, i.e., blood pressure and heart rate,at Screening baseline and 15(±5) min post dosing for reversibility
Time Frame: screening and 15 minutes post dose
screening and 15 minutes post dose
Vital signs, i.e., blood pressure (SBP/DBP) and heart rate (HR), at: Pre-dose baseline, and 15(±5) min and 360(±15) post-dose, at each Study Visit.
Time Frame: 360 minutes post dose
360 minutes post dose
Post-dose 20(±5) min ECG recordings (Routine and QT, QTc analysis) at each Study Visit, compared to the Screening baseline recording.
Time Frame: 20 minutes post dose
20 minutes post dose
Data for physical examinations, CBC, serum comprehensive metabolic panel, and urinalysis for all subjects, and urinary pregnancy test for women of child-bearing potential
Time Frame: Screening and end of study
Screening and end of study
Monitoring of adverse drug events (ADE)
Time Frame: Ongoing through End of Study
Ongoing through End of Study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amphastar Pharmaceuticals, Inc.

Investigators

  • Study Chair: Jim Shi, M.D., Ph.D., Amphastar Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2009

Primary Completion (ACTUAL)

December 1, 2009

Study Completion (ACTUAL)

December 1, 2009

Study Registration Dates

First Submitted

December 1, 2009

First Submitted That Met QC Criteria

December 1, 2009

First Posted (ESTIMATE)

December 3, 2009

Study Record Updates

Last Update Posted (ACTUAL)

May 16, 2018

Last Update Submitted That Met QC Criteria

May 14, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • API-E004-CL-A

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Asthma

Clinical Trials on E004 (epinephrine inhalation aerosol), 90 mcg/actuation

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Finland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe