Safety and Tolerability Study of Levalbuterol HFA and Racemic Albuterol HFA in Pediatrics Subjects With Asthma

• Percent change in FEV1 (from visit pre-dose to each post dose measure) [ Time Frame: Days 0, 7, 10 ] [ Designated as safety issue: No ]
• Percent change in FVC (from visit pre-dose to each post dose measure) [ Time Frame: Days 0, 7, 10 ] [ Designated as safety issue: No ]
• Percent change in FEF25-75% (from visit pre-dose to each post dose measure) [ Time Frame: Days 0, 7, 10 ] [ Designated as safety issue: No ]
• Number of cumulative actuations received [ Time Frame: Days 0, 7, 10 ] [ Designated as safety issue: No ]

• 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)
  Other Names:

  • Xopenex HFA MDI
  • albuterol HFA MDI
• 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)
  Other Names:

  • albuterol HFA MDI
  • Xopenex HFA MDI

• 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.

  Intervention: Drug: Levalbuterol HFA MDI followed by Racemic albuterol HFA MDI
• 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.
  Intervention: Drug: Racemic Albuterol followed by levalbuterol HFA MDI

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.