Clinical Trial: Single-Dose Cross-Over Study of the Effects of Albuterol-HFA in Exercise Induced Bronchoconstriction

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Randomized, Double-Blind, Controlled, Single-Dose, Three-Treatment, Cross-Over Study of The Protective Effects Of Albuterol-HFA In Preventing Exercise-Induced Bronchoconstriction In Adolescent And Adu

Brief Summary: This clinical study will evaluate and establish the protective effects of Amphastar's Albuterol Sulfate HFA Inhalation Aerosol (Albuterol-HFA), in preventing exercise-induced bronchoconstriction (EIB) in adolescent and adult asthmatic patients, in comparison with (1) Proventil®-HFA (Reference drug and Active Control ), and (2) Placebo-HFA control (HFA propellant only). Safety of the test drug, Albuterol-HFA, will also be evaluated in comparison to the Active and Placebo Controls. Analyses will be performed to determine if the Armstrong's Albuterol-HFA has resulted in a significant bronchoprotective effect, with attenuated Max % Fall in FEV1, in comparison to the Placebo-HFA control.

Detailed Summary:

The prevalence of exercise-induced bronchoconstriction (EIB) has been reported to be around 70% to 75% among patients with clinically established asthma. Airway cooling and drying are thought to cause the release of inflammatory mediators, such as histamine and leukotrienes, which then mediate clinical EIB symptoms. Pretreatment with a variety of medications will ameliorate EIB. Albuterol has been found to be more effective in minimizing EIB than theophylline, ipratropiom, cromoglycate, etc. Tested using a treadmill exercise challenge, the newer formulations of albuterol MDI with HFA as propellant have been demonstrated to be as effective as those with CFC as propellant in protecting asthma patients from EIB in children and adults.

As a part of the Amphastar Pharmaceuticals' clinical development plan, the current study examines the clinical efficacy of A004, Armstrong Pharmaceuticals' Albuterol HFA oral inhalation MDI, in preventing EIB in adolescent and adult asthmatic patients.

This is a randomized, double-blind, active and placebo-controlled, three-treatment, cross-over study, to be conducted in adolescent and adult patients with mild to moderate asthma and demonstrable EIB.

All subjects will be screened against the inclusion/exclusion criteria for enrollment. A computer-generated randomization code will be created by the Amphastar Pharmaceuticals' IT Department, so that each enrolled subject will receive all three double-blinded treatments in randomized sequence. Each treatment is followed by a standardized exercise challenge and a series of FEV1 measurements during the 90 min post-exercise period. The three crossover Treatment Arms are:

  • Treatment T (Armstrong's Test Drug: Albuterol-HFA);<
    Sponsor: Amphastar Pharmaceuticals, Inc.

    Current Primary Outcome: The maximum percentage fall in FEV1, from the Pre-Exercise FEV1, between Albuterol-HFA and Placebo-HFA. [ Time Frame: 90 minutes post exercise ]

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Evaluation of relative broncho-protective efficacy of Albuterol-HFA, in comparison to the active comparator, Proventil®-HFA, using the Max % fall in Post-Exercise FEV1, from the Pre-exercise FEV1 [ Time Frame: 90 minutes post exercise ]
    • Pre-exercise FEV1 values (volume in Liters, recorded ), indicative of bronchodilator responsiveness. [ Time Frame: 20-30 min post dose ]
    • Number and percentage of subjects who demonstrate a <20.0% fall in FEV1, from the Pre-exercise FEV1. [ Time Frame: 90 min post-exercise ]
    • Area Under-the-Curve of percentage fall in FEV1, from the Pre-exercise FEV1. [ Time Frame: 90 min post-exercise ]
    • Time to recovery, as the time point where FEV1 recovers from maximum percent fall in FEV1 to be within 5.0% of the Pre-Exercise FEV1 values. [ Time Frame: concurrent with study visit ]
    • Number of subjects who cannot complete the exercise at specified intensity and length, due to asthma symptoms. [ Time Frame: concurrent with study visit ]
    • Number of subjects requiring B2-agonist rescue inhalations during exercise, and during the 90 min post-exercise period. [ Time Frame: 90 minutes post exercise ]
    • The following baseline and post-dose safety parameters before and after each exercise-challenge tests will be assessed: Vital signs: blood pressure (SBP/DBP) and heart rate (HR). [ Time Frame: concurrent with study visit ]
    • 12-lead ECG: HR, QT and QTc intervals, before and after treatment with Albuterol-HFA, versus the active control, and placebo control. [ Time Frame: concurrent with study visit ]
    • Pre-study (Screening) and End-of-Study laboratory tests for CBC, blood chemistry panel, urinalysis and urine pregnancy test. [ Time Frame: Throughout study ]
    • Adverse events and side effects will be documented when observed by investigators or reported by subjects. [ Time Frame: throughout study ]


    Original Secondary Outcome: Same as current

    Information By: Amphastar Pharmaceuticals, Inc.

    Dates:
    Date Received: March 7, 2008
    Date Started: February 2008
    Date Completion:
    Last Updated: July 11, 2013
    Last Verified: July 2013