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

This study has been terminated.
(Optimization of protocol)
Sponsor:
Information provided by (Responsible Party):
Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01025648
First received: December 1, 2009
Last updated: July 11, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: E004 (epinephrine inhalation aerosol), 90 mcg/actuation
Drug: E004 Placebo
Drug: E004 (epinephrine inhalation aerosol), 125 mcg
Drug: E004 (epinephrine inhalation aerosol), 220 mcg
Drug: epinephrine inhalation aerosol, CFC propelled
Drug: E004 (epinephrine inhalation aerosol), 160 mcg
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 1/2 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 of E004 in Asthma Patients

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Dose response relationship of Epinephrine HFA-MDI, analyzed using efficacy data from all E004 doses. [ Time Frame: 360 minutes post dose ] [ Designated as safety issue: No ]
  • AUC of FEV1 volume post-dose changes (Δ Volume) from the Pre-dose baseline. [ Time Frame: 306 minutes post dose ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • The peak bronchodilator response (Fmax), defined as the maximum post-dose FEV1 percent change. [ Time Frame: 360 minutes post dose ] [ Designated as safety issue: No ]
  • The time to peak FEV1 effect (Tmax), defined as the time of Fmax. [ Time Frame: 360 minutes post dose ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Response Rate of responders who demonstrate 12.0 percent or greater FEV1 changes from the Pre-dose baseline. [ Time Frame: 360 minutes post dose ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Monitoring of adverse drug events (ADE) [ Time Frame: Ongoing through End of Study ] [ Designated as safety issue: Yes ]

Enrollment: 9
Study Start Date: December 2009
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Primatene Mist HFA
Experimental: T2 - E004 125 mcg/actuation
125 mcg E004 (epinephrine inhalation aerosol), 2 actuations, single dose crossover, 1 - 14 day washout period
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 Name: 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 Name: 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 Name: 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 Name: 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

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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;
  2. Demonstrating a baseline forced expiratory volume in 1 second (FEV1) at 50-90 percent of predicted normal at Screening;
  3. 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;
  4. Females of child-bearing potential must be non-pregnant, non-lactating, and practicing a clinically acceptable form of birth control;
  5. Demonstration of proficiency in the use of a MDI inhaler after training;
  6. 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01025648

Sponsors and Collaborators
Amphastar Pharmaceuticals, Inc.
Investigators
Study Chair: Jim Shi, M.D., Ph.D. Amphastar Pharmaceuticals, Inc.
  More Information

Publications:
Dauphinee B, Tashkin DP, et al: Placebo-controlled evaluation of the speed of onset of epinephrine metered-dose aerosol (Primatene Mist) in mild to moderate asthmatics. Am J Respir Crit Care Med, 149:A204, 1994
Westfall TC, Westfall DP: Adrenergic agonists and antagonists, in Brunton LL, Lazo JS, Parker KL (eds): Goodman & Gilman's Ther Pharmacological Basis of Therapeitucs, 11th Ed. P237-296, 1986

Responsible Party: Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01025648     History of Changes
Other Study ID Numbers: API-E004-CL-A
Study First Received: December 1, 2009
Last Updated: July 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Amphastar Pharmaceuticals, Inc.:
Mild to Moderate Asthma
Dyspnea
Wheezing
Status Asthmaticus

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 22, 2014