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Albuterol HFA MDI in Pediatric Participants With Asthma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier:
NCT00577655
First received: December 18, 2007
Last updated: September 2, 2016
Last verified: September 2016
  Purpose
The primary objective of this study is to evaluate the chronic-dose and efficacy of Albuterol-HFA-MDI relative to placebo in pediatric asthmatics.

Condition Intervention Phase
Asthma
Drug: Albuterol
Drug: Placebo
Drug: Proventil® HFA
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 3 Study to Evaluate the Chronic-dose Safety and Efficacy of Albuterol-HFA-MDI Relative to Placebo in Pediatric Asthmatics

Resource links provided by NLM:


Further study details as provided by Teva Pharmaceutical Industries:

Primary Outcome Measures:
  • Maximum Percent Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Observed up to Two Hours Post Dose (FEV1max%0-2) on Day 22 [ Time Frame: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing on Day 22 or last observation ] [ Designated as safety issue: No ]

    The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. A standardized spirometer was used with the subject in the sitting or standing position (orientation had to be consistent for each subject during study visits) and wearing a nose clip. Whenever possible, evaluations were performed by the same respiratory therapist on the same calibrated spirometer at approximately the same time (±2 hrs).

    The maximum percent change from baseline in FEV1 observed up to 2 hours following completion of dosing using Day 22 baseline. The baseline FEV1 was defined as the average of the two test-day pre-dose baseline FEV1 values.

    The reason for the two primary endpoints was that FEV1 is difficult to obtain in children below 7 years of age.


  • Maximum Percent Change From Baseline in Peak Expiratory Flow (PEF) Observed up to Two Hours Post Dose (PEFmax%0-2) on Day 22 [ Time Frame: 30±5 and 5±2 minutes prior to dosing, and at 7.5±2, 20±5, 35±5, 50±5, 65±10, 125±10 post dosing on Day 22 or last observation ] [ Designated as safety issue: No ]

    The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. A standardized spirometer was used with the subject in the sitting or standing position (orientation had to be consistent for each subject during study visits) and wearing a nose clip. Whenever possible, evaluations were performed by the same respiratory therapist on the same calibrated spirometer at approximately the same time (±2 hrs).

    The maximum percent change from baseline in the PEF observed up to 2 hours following completion of dosing using Day 22 baseline. The baseline PEF was defined as the average of the test-day pre-dose baseline PEF values.

    The reason for the two primary endpoints was that FEV1 is difficult to obtain in children below 7 years of age.



Secondary Outcome Measures:
  • Maximum Percent Change From Baseline in Forced Expiratory Volume in One Second (FEV1) up to Two Hours Post-Dose (FEV1max%0-2, %) on Study Days 1 and 22 Using Observed Cases [ Time Frame: Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing ] [ Designated as safety issue: No ]

    The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. A standardized spirometer was used with the subject in the sitting or standing position (orientation had to be consistent for each subject during study visits) and wearing a nose clip. Whenever possible, evaluations were performed by the same respiratory therapist on the same calibrated spirometer at approximately the same time (±2 hrs).

    The maximum percent change from baseline in FEV1 observed up to 2 hours following completion of dosing using test day baseline. The baseline FEV1 was defined as the average of the two test-day pre-dose baseline FEV1 values.


  • Maximum Percent Change From Baseline in Peak Expiratory Flow (PEF) up to Two Hours Post-Dose (PEFmax%0-2) on Study Days 1 and 22 Using Observed Cases [ Time Frame: Days 1 and 22: 30±5 and 5±2 minutes prior to dosing, and 7.5±2, 20±5, 35±5, 50±5, 65±10, 125±10 post dosing ] [ Designated as safety issue: No ]

    The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. A standardized spirometer was used with the subject in the sitting or standing position (orientation had to be consistent for each subject during study visits) and wearing a nose clip. Whenever possible, evaluations were performed by the same respiratory therapist on the same calibrated spirometer at approximately the same time (±2 hrs).

    The maximum percent change from baseline in the PEF observed up to 2 hours following completion of dosing on study days 1 and 22. The baseline PEF was defined as the average of the test-day pre-dose baseline PEF values.

    The reason for the two primary endpoints was that FEV1 is difficult to obtain in children below 7 years of age.


  • Baseline Adjusted Area-under-the-Effect Curve for Percent of Predicted Forced Expiratory Volume in One Second (FEV1) Over 6 Hours Post-dose on Day 22 Using Both Day 1 and Day 22 Baselines [ Time Frame: Baseline (Day 1 or Day 22: 35±5 and 10±2 minutes prior to dosing), Day 22 (5±2, 15±5, 30±5, 45±5, 60±10, 120±10, 240±10, and 360±10 minutes post-dosing or last observation) ] [ Designated as safety issue: No ]

    The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. Values are then expressed as the percentage of FE1 values predicted for a 'normal' population. Predicted FEV1 values were computed and adjusted for age, height and gender according to Eigen et al. for subjects 4-5 years of age and to Quanjer et al. for subjects aged 6-11 years using American Thoracic Society (ATS) criteria.

    The area under-the-effect curves for percent-predicted FEV1 were calculated according to the trapezoidal rule and were based on actual (not scheduled) measurement times.


  • Baseline-Adjusted Area-under-the Effect Curve for Peak Expiratory Flow (PEF) Over 6 Hours Post-dose on Day 22 Using Both Day 1 and Day 22 Baselines [ Time Frame: Baseline (Day 1 or Day 22: 30±5 and 5±2 minutes prior to dosing Day 22: 7.5±2, 20±5, 35±5, 50±5, 65±10, 125±10 post dosing or last observation ] [ Designated as safety issue: No ]

    The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown.

    The area under-the-effect curves for PEF were calculated according to the trapezoidal rule and were based on actual (not scheduled) measurement times.


  • Maximum Percent-Predicted FEV1 (Max PPFEV1, %) Observed up to Two Hours Following Completion of Dosing on Study Days 1 and 22 (Observed Case) [ Time Frame: Days 1 and 22: 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing ] [ Designated as safety issue: No ]
    The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. Values are then expressed as the percentage of FE1 values predicted for a 'normal' population. Predicted FEV1 values were computed and adjusted for age, height and gender according to Eigen et al. for subjects 4-5 years of age and to Quanjer et al. for subjects aged 6-11 years using American Thoracic Society (ATS) criteria.

  • Time To Maximum Forced Expiratory Volume in One Second (FEV1) Over Six Hours Post-Dose On Days 1 and 22 [ Time Frame: Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5, 45±5, 60±10, 120 ±10 post dosing ] [ Designated as safety issue: No ]

    The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters.

    Time to maximum FEV1 is defined as the number of minutes required for the baseline FEV1 to increase to the highest FEV1 post dose during the 6 hour observation period.

    Median time and confidence intervals obtained via separate Kaplan-Meier estimates for each study day.


  • Time To Maximum Peak Expiratory Flow (PEF) Over Six Hours Post-Dose On Days 1 and 22 [ Time Frame: Days 1 and 22: 30±5 and 5±2 minutes prior to dosing, and 7.5±2, 20±5, 35±5, 50±5, 65±10, 125±10 post dosing ] [ Designated as safety issue: No ]

    The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown.

    Time to maximum PEF is defined as the number of minutes required for the baseline PEF to increase to the highest PEF post-dose for the 6 hour observation period. Median time and confidence intervals obtained via separate Kaplan-Meier estimates for each study day.


  • Participant Responses: Percentage of Participants With a >=15% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22 [ Time Frame: Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing ] [ Designated as safety issue: No ]

    The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. This outcome counts participants who responded to therapy by obtaining a >+15% increase in FEV1 within 30 minutes of dose.

    The baseline FEV1 was defined as the average of the two test-day pre-dose baseline FEV1 values.


  • Participant Responses: Percentage of Participants With a >=12% Increase in Baseline FEV1 Within 30 Minutes Post-Dose on Days 1 and 22 [ Time Frame: Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing ] [ Designated as safety issue: No ]

    The FEV1 test is conducted by having a person empty their lungs of air into a mouthpiece attached to a sensor that measures the amount of air blown measured in liters. This outcome counts participants who responded to therapy by obtaining a >+12% increase in FEV1 within 30 minutes of dose.

    The baseline FEV1 was defined as the average of the two test-day pre-dose baseline FEV1 values.


  • Participant Responses: Percentage of Participants With a >=15% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22 [ Time Frame: Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing ] [ Designated as safety issue: No ]

    The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. This outcome counts participants who responded to therapy by obtaining a >+15% increase in PEF within 30 minutes of dose.

    The baseline PEF was defined as the average of the two test-day pre-dose baseline PEF values.


  • Participant Responses: Percentage of Participants With a >=12% Increase in Baseline PEF Within 30 Minutes Post-Dose on Days 1 and 22 [ Time Frame: Days 1 and 22: 35±5 and 10±2 min prior to dosing, and at 5±2, 15±5, 30±5 post dosing ] [ Designated as safety issue: No ]

    The PEF test is conducted by having a person blow as hard as they can into a mouthpiece attached to a sensor that measures the rate of air blown. This outcome counts participants who responded to therapy by obtaining a >+12% increase in PEF within 30 minutes of dose.

    The baseline PEF was defined as the average of the two test-day pre-dose baseline PEF values.


  • Weekly Average Highest (Worst) Daily Asthma Symptom Scores for Weeks 1, 2 and 3 [ Time Frame: Weeks 1, 2, 3 ] [ Designated as safety issue: No ]

    Highest daily asthma symptom scores by study week. For this assessment, patients self-evaluate and record on the diary card the following asthma symptoms experienced during the day (i.e. last 12-14 hours): wheeze, shortness of breath, cough, tightness of chest. The worst of these symptoms were scored daily on a four-point scale:

    • 0 = No symptoms occurred
    • 1 = Symptom occurred but did not interfere with daily activity
    • 2 = Symptom occurred but was sometimes annoying or interfered with daily activity
    • 3 = Symptom present even at rest and was annoying or interfered with daily activity

  • The Number of Asthma-Related Nocturnal Awakenings Per Week Requiring the Use of Rescue Medication [ Time Frame: Run-in (Days -21 to -1), Weeks 1, 2, 3 ] [ Designated as safety issue: No ]
    Participants recorded every morning on awakening the number of asthma-related nocturnal awakenings requiring use of rescue medication that occurred during the previous night.

  • Weekly Average Peak Expiratory Flow (PEF) Obtained Pre-Dose Each Morning [ Time Frame: Weeks 1, 2, 3 ] [ Designated as safety issue: No ]
    Participants measured their PEF as trained by taking as deep a breath as possible, placing their mouth firmly around the mouthpiece of the flow meter to form a tight seal, and exhaling as hard and as fast as possible. Subjects repeated the process twice at intervals of approximately 30 seconds, and then recorded the highest of the three PEF values on the diary card.

  • Weekly Average Number of Puffs of Rescue Medication Taken Each Day for Study Weeks 1, 2 and 3 [ Time Frame: Weeks 1, 2, 3 ] [ Designated as safety issue: No ]
    Participants recorded every morning on awakening the number of asthma-related nocturnal awakenings requiring use of rescue medication that occurred during the previous night and the number of puffs of rescue albuterol used during the night after going to bed. At the end of each day, the number of puffs of albuterol rescue medication used during the day were recorded.


Enrollment: 103
Study Start Date: August 2007
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Albuterol
Albuterol-HFA-MDI 180 mcg, four times a day (total daily albuterol dose of 720 mcg) for 21 days. HFA-MDI refers to a metered-dose inhaler (MDI) utilizing a hydrofluoroalkane (HFA) propellant.
Drug: Albuterol
Albuterol HFA MDI 180 mcg four times a day (q.i.d) for a total daily albuterol dose of 720 mcg for 21 days.
Other Names:
  • ProAir® HFA
  • Albuterol Sulfate
Drug: Proventil® HFA
Proventil® HFA (albuterol sulfate) Inhalation Aerosol (Key Pharmaceuticals) was used as rescue medication in this study. The rescue medication was over-labeled with instructions for emergency use in which subjects were instructed to self-administer up to two puffs every 20 minutes to a maximum of six puffs for any given episode while attempting to seek medical assistance.
Other Name: albuterol sulfate
Placebo Comparator: Placebo
A placebo of a metered-dose inhaler (MDI) utilizing a hydrofluoroalkane (HFA) propellant. (Hereafter noted as "Placebo-HFA-MDI.")
Drug: Placebo
Placebo HFA MDI four times a day (q.i.d) for 21 days.
Drug: Proventil® HFA
Proventil® HFA (albuterol sulfate) Inhalation Aerosol (Key Pharmaceuticals) was used as rescue medication in this study. The rescue medication was over-labeled with instructions for emergency use in which subjects were instructed to self-administer up to two puffs every 20 minutes to a maximum of six puffs for any given episode while attempting to seek medical assistance.
Other Name: albuterol sulfate

  Eligibility

Ages Eligible for Study:   4 Years to 11 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female child aged 4-11 years, inclusive Asthma of a minimum of six months duration that has been stable for at least four weeks prior to screening.

Exclusion Criteria:

  • Hospitalization for acute asthma exacerbation greater than two years in 12 months prior to screening and/or received ER treatment or hospitalization for asthma exacerbation.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00577655

Locations
United States, California
Pediatric Care Medical Group, Inc.
Huntington Beach, California, United States, 92647
California Allergy & Asthma Medical Group
Palmdale, California, United States, 93551
Center for Clinical Trials, LLC
Paramount, California, United States, 90723
Integrated Research Group, Inc
Riverside, California, United States, 92506
Center for Clinical Trials of Sacramento
Sacramento, California, United States, 95823
United States, Florida
Carlos Piniella, MD
Miami, Florida, United States, 33157
United States, Illinois
Sneeze, Wheeze & Itch Associates, Inc.
Normal, Illinois, United States, 61761
United States, New York
Asthma & Allergy Associates, PC
Elmira, New York, United States, 14901
ENT & Allergy Associates
Newburgh, New York, United States, 12550
St. Elizabeth's Children Health Center
Utica, New York, United States, 13502
United States, North Carolina
Regional Allergy & Asthma Consultants
Asheville, North Carolina, United States, 28801
United States, Oregon
Clinical Research Institute of Southern Oregan, PC
Medford, Oregon, United States, 97504
United States, Virginia
Virginia Adult & Pediatric Allergy & Asthma
Richmond, Virginia, United States, 23229
Sponsors and Collaborators
Teva Branded Pharmaceutical Products, R&D Inc.
Investigators
Study Director: Teva Study Physician MD TEVA
  More Information

Responsible Party: Teva Branded Pharmaceutical Products, R&D Inc.
ClinicalTrials.gov Identifier: NCT00577655     History of Changes
Other Study ID Numbers: IXR-302-25-105 
Study First Received: December 18, 2007
Results First Received: July 21, 2009
Last Updated: September 2, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Teva Pharmaceutical Industries:
Pediatric, asthma, albuterol-HFA and Placebo

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Albuterol
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 02, 2016