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

The purpose of this study is to compare the safety and tolerability of levalbuterol HFA metered dose inhaler (MDI) versus racemic albuterol HFA MDI in pediatric subjects 4-11 years of age with asthma

Study Type: Interventional

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

Study Primary Completion Date: July 2003

A randomized, double-blind, active-controlled multicenter, two-way crossover study of HFA levalbuterol (with and without a spacer) in subjects 4-11 years of age with asthma

Intervention(s) in this Clinical Trial

• Drug: Levalbuterol HFA MDI followed by Racemic albuterol HFA MDI
  • (a) Subjects will receive both treatments: (a) levalbuterol HFA MDI; 45 micrograms (16 cumulative doses); followed by (b) racemic albuterol HFA MDI; 90 micrograms (16 cumulative doses)
• Drug: Racemic Albuterol followed by levalbuterol HFA MDI
  • (a) Subjects will receive both treatments: (a) racemic albuterol HFA MDI; 90 micrograms (16 cumulative doses) followed by (b) levalbuterol HFA MDI; 45 micrograms (16 cumulative doses)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • Subjects will receive both treatments: (a) levalbuterol HFA MDI; 45 micrograms (8 cumulative doses); followed by (b) racemic albuterol HFA MDI; 90 micrograms (8 cumulative doses). The first treatment will be administered, followed by a 7 ±2 days washout period, after which the second of the two treatments will be administered. Cumulative dosing will occur according to the following schedule: 1 puff at 0 and 30 minutes, 2 puffs at 60 minutes, 4 puffs at 90 minutes and 8 puffs at 120 minutes. Treatment will be administered with an AeroChamber Plus ™ spacer for the first cohort (spacer cohort) of subjects and without the AeroChamber Plus ™ spacer (non-spacer cohort) for the second cohort of subjects.
• Active Comparator: B
  • Subjects will receive both treatments: (a) racemic albuterol HFA MDI; 90 micrograms (16 cumulative doses) followed by (b) levalbuterol HFA MDI; 45 micrograms (16 cumulative doses) The first treatment will be administered, followed by a 7 ±2 days washout period, after which the second of the two treatments will be administered. Cumulative dosing will occur according to the following schedule: 1 puff at 0 and 30 minutes, 2 puffs at 60 minutes, 4 puffs at 90 minutes and 8 puffs at 120 minutes. Treatment will be administered with an AeroChamber Plus ™ spacer for the first cohort (spacer cohort) of subjects and without the AeroChamber Plus ™ spacer (non-spacer cohort) for the second cohort of subjects.

Primary Measures

• Increases from visit pre-dose to each post-dose dose measurement in heart rate, blood pressure (systolic and diastolic), potassium and glucose
  • Time Frame: 0, 7, 10 days
    Safety Issue?: Yes

Secondary Measures

• Percent change in FEV1 (from visit pre-dose to each post dose measure)
  • Time Frame: Days 0, 7, 10
    Safety Issue?: No
• Percent change in FVC (from visit pre-dose to each post dose measure)
  • Time Frame: Days 0, 7, 10
    Safety Issue?: No
• Percent change in FEF25-75% (from visit pre-dose to each post dose measure)
  • Time Frame: Days 0, 7, 10
    Safety Issue?: No
• Number of cumulative actuations received
  • Time Frame: Days 0, 7, 10
    Safety Issue?: No

Inclusion Criteria:

• Subject, male or female, must be between the ages of 4 to 11 years, inclusive, at the time of consent.
• Female subjects who are 8 years of age or older will have a negative serum pregnancy test at study start.
• 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 or have one taken within 12 months prior to randomization may be used.
• 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 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 prior to study start, or who is currently participating in another clinical trial.
• Subject whose schedule prevents him or her from taking the first daily dose of study medication and/or starting study visits before 9 AM.
• 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.
• 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 2 weeks prior to study start.
• Subject 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: 4 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 September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00684866

Study ID Number: 051-311

ClinicalTrials.gov Identifier: NCT00684866

Health Authority: United States: Food and Drug Administration