Official Title: “A Dose Response Study of Levalbuterol and Racemic Albuterol HFA MDI in Pediatric Subjects With Asthma”

The purpose of this study is to investigate, using an exercise challenge approach, the dose response of levalbuterol HFA MDI in pediatric subjects with asthma

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: June 2003

A randomized, double-blind, active controlled, multicenter, parallel treatment, 3x3 dose level crossover study evaluating the dose response of levalbuterol in pediatric subjects between the ages of 6 and 11, inclusive with exercise induced bronchoconstriction.

Intervention(s) in this Clinical Trial

• Drug: Levalbuterol HFA MDI
  • levalbuterol 45 µg (1 actuation of 45 µg); (b) levalbuterol 90 µg (2 actuation of 45 µg) and (c) levalbuterol 180 µg (4 actuations of 45 µg each). Arm #A Xopenex HFA MDI
• Drug: Racemic Albuterol
  • racemic albuterol 90 µg (1 actuation of 90 µg); (b) racemic albuterol 180 µg (2 actuations of 90 µg) and (c) racemic albuterol 360 µg (4 actuations of 90 µg). Arm #B Proventil HFA MDI

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • Subjects randomized to the levalbuterol arm will complete 1 of 6 possible randomization sequences containing (a) levalbuterol 45 µg (1 actuation of 45 µg); (b) levalbuterol 90 µg (2 actuation of 45 µg) and (c) levalbuterol 180 µg (4 actuations of 45 µg each). Subjects will receive treatment, according to the randomization sequence, followed by a 5±2 day washout.
• Active Comparator: B
  • Subjects randomized to racemic albuterol will complete 1 of 6 possible randomization sequences containing (a) racemic albuterol 90 µg (1 actuation of 90 µg); (b) racemic albuterol 180 µg (2 actuations of 90 µg) and (c) racemic albuterol 360 µg (4 actuations of 90 µg). Subjects will receive treatment, according to the randomization sequence, followed by a 5±2 day washout.

Primary Measures

• Maximum percent decrease in FEV1 from visit post-dose/pre-challenge FEV1
  • Time Frame: Days -7, 0, 5, 10, 15
    Safety Issue?: No

Secondary Measures

• Area under the percent decrease from visit post-dose/pre-challenge FEV1 curve
  • Time Frame: Days -7, 0, 5, 10, 15
    Safety Issue?: No
• Area under the percent decrease from visit pre-dose FEV1 curve.
  • Time Frame: Days -7, 0, 5, 10, 15
    Safety Issue?: No
• Minimum percent change in FEV1 from visit pre-dose FEV1.
  • Time Frame: Days -7, 0, 5, 10, 15
    Safety Issue?: No
• Minimum percent change in FEV1 from visit post dose/pre-challenge FEV1
  • Time Frame: Days -7, 0, 5, 10, 15
    Safety Issue?: No
• percent change in FEV1 from visit predose to the post-dose/pre-challenge FEV1
  • Time Frame: Days -7, 0, 5, 10, 15
    Safety Issue?: No
• Time to recovery (min), Protected/Unprotected Subjects Counts
  • Time Frame: Days -7, 0, 5, 10, 15
    Safety Issue?: No
• Area under the percent decrease from visit post-dose/pre-challenge FVC,
  • Time Frame: Days -7, 0, 5, 10, 15
    Safety Issue?: No
• Maximum percent decrease in FVC from visit post-dose/pre-challenge FVC
  • Time Frame: Days -7, 0, 5, 10, 15
    Safety Issue?: No
• Minimum percent change in FVC from pre-dose FVC
  • Time Frame: Days -7, 0, 5, 10, 15
    Safety Issue?: No
• Area under the percent decrease from visit post-dose/pre-challenge FEF25%-75% curve
  • Time Frame: Days -7, 0, 5, 10, 15
    Safety Issue?: No
• Maximum percent decrease in FEF25-75% from visit post-dose/pre-challenge FEF25-75%
  • Time Frame: Days -7, 0, 5, 10, 15
    Safety Issue?: No
• Minimum percent change in FEF25%-75% from visit pre-dose FEF25-75%.
  • Time Frame: Days -7, 0, 5, 10, 15
    Safety Issue?: No

Inclusion Criteria:

• Subject, male or female, must be between the ages of 6 to 11 years, inclusive, at the time of consent.
• Female subjects who are 8 years of age or older must have a negative serum pregnancy test.
• Subject must have a documented diagnosis of asthma for a minimum of 6 months prior to study start
• Subject must be in good health with the exception of their reversible airways disease and not suffering from any chronic condition that might affect their respiratory function.
• Subject must have a chest X-ray for the study or within 12 months prior to randomization.
• Subject's parent/legal guardian must be able to complete the diary cards and medical event calendars reliably on a daily basis and understand dosing instructions. Any minor subject who is not able to do this must have a parent/legal guardian who can assist them during the study with these activities.

Exclusion Criteria:

• Female subject who is pregnant or lactating.
• Subject who has participated in an investigational drug study within 30 days of study start, or who is currently participating in another clinical trial.
• Subject whose schedule prevents him or her from starting study visits before 2:30-4:00
• PM.
• Subject who is unwilling or physically unable to perform the exercise challenges as described in the protocol.
• Subject who has travel commitments during the study that would interfere with trial measurements or compliance or both.
• Subject who has a history of hospitalization for asthma within 4 weeks prior to study start, or who is scheduled for in-patient hospitalization, including elective surgery during the course of the trial.
• Subject with a known sensitivity to levalbuterol or racemic albuterol, or any of the excipients contained in any of these formulations.
• Subject using any prescription drug with which albuterol sulfate administration is contraindicated.
• Subject with currently diagnosed life-threatening asthma defined as a history of asthma episodes requiring intubation, associated with hypercapnia, respiratory arrest, or hypoxic seizures within 3 months prior to study start.
• Subject with a history of cancer (exception: basal cell carcinoma in remission).
• Subject with hyperthyroidism, diabetes, hypertension, cardiac diseases or seizure disorders.
• Subject with a history of substance abuse or drug abuse within 12 months preceding study start.
• Subject with a history of cigarette smoking or use of any tobacco products.
• Subject with a documented history of bronchopulmonary aspergillosis or any form of allergic alveolitis.
• Subject who has suffered from a clinically significant upper or lower respiratory tract infection in the 3 weeks prior to study start.
• Subjects with unstable asthma; or who have had a change in asthma therapy; or a visit to the Emergency Department or hospital for worsening asthma within 4 weeks.
• Subject who is a staff member or relative of a staff member.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 6 Years

Maximum Age for this Clinical Trial: 11 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Sepracor, Inc.

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00685347

Study ID Number: 051-312

ClinicalTrials.gov Identifier: NCT00685347

Health Authority: United States: Food and Drug Administration