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

Information source: Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Asthma

Intervention: 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 (Drug)

Phase: Phase 1/Phase 2

Status: Terminated

Sponsored by: Amphastar Pharmaceuticals, Inc.

Official(s) and/or principal investigator(s):
Jim Shi, M.D., Ph.D., Study Chair, Affiliation: Amphastar Pharmaceuticals, Inc.

Summary

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.

Clinical Details

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: 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).

Secondary outcome:

Dose response relationship of Epinephrine HFA-MDI, analyzed using efficacy data from all E004 doses.

AUC of FEV1 volume post-dose changes (Δ Volume) from the Pre-dose baseline.

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.

The peak bronchodilator response (Fmax), defined as the maximum post-dose FEV1 percent change.

The time to peak FEV1 effect (Tmax), defined as the time of Fmax.

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.

Response Rate of responders who demonstrate 12.0 percent or greater FEV1 changes from the Pre-dose baseline.

Vital signs, i.e., blood pressure and heart rate,at Screening baseline and 15(±5) min post dosing for reversibility

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.

Post-dose 20(±5) min ECG recordings (Routine and QT, QTc analysis) at each Study Visit, compared to the Screening baseline recording.

Data for physical examinations, CBC, serum comprehensive metabolic panel, and urinalysis for all subjects, and urinary pregnancy test for women of child-bearing potential

Monitoring of adverse drug events (ADE)

Eligibility

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

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.

Locations and Contacts

Additional Information

Related publications:

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Dickinson BD, Altman RD, Deitchman SD, Champion HC. Safety of over-the-counter inhalers for asthma: report of the council on scientific affairs. Chest. 2000 Aug;118(2):522-6.

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Armstrong Pharmaceuticals: Package Insert of Epinephrine Inhalation Aerosol USP, a CFC-MDI, current as of 2008

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NHLBI/NAEPP (National Heart, Lund and Blood Institute; Natuinak /asthma Education and Prevention Program) Expert Panel Report 3 (2007): Guidelines for the diagnosis and management of asthma, Section 3, Component 1, Figure 3-4C:

Wyeth Consumer Healthcare: 2005N-0374, Use of ozone-depleting substances: Essential-use determination of over-the-counter (OTC) epinephrine metered dose inhalers. Submitted to teh Nonprescription Drugs and Pulmonary-Allergy Drugs Advisory Committees. Dec 2005.

Global Initiative for Asthma (GINA): Pocket guide for asthma management and prevention,

Starting date: December 2009
Last updated: July 11, 2013

Page last updated: August 20, 2015

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