4-Week Study of Efficacy, Safety and PK of Albuterol-HFA Versus Proventil-HFA in Pediatric Asthma - Full Text View

Sponsored by:	Amphastar Pharmaceuitcals, Inc.
Information provided by:	Amphastar Pharmaceuitcals, Inc.
ClinicalTrials.gov Identifier:	NCT00634517

Purpose

This 4-week clinical study evaluates the efficacy and safety of Albuterol Sulfate HFA Inhalation Aerosol in comparison with the Active Control, Proventil-HFA (3M Pharmaceuticals, Inc) in pediatric patients (4-11 years old) with mild-to-moderate asthma. In addition, pharmacokinetic profile in this population will be evaluated using a population PK approach with sparse blood samples.

Condition	Intervention	Phase
Asthma	Drug: Armstrong Albuterol Sulfate Inhalation Aerosol Drug: Albuterol Sulfate Inhalation Aerosol	Phase III

MedlinePlus related topics: Asthma

Drug Information available for: Albuterol Levalbuterol hydrochloride Albuterol sulfate Levalbuterol tartrate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Multi-Center, Randomized, Double-Blind, Active-Controlled, Parallel Group, 4-Week Study to Evaluate the Efficacy, Safety and PK of Albuterol-HFA Versus Proventil-HFA in Pediatric Patients With Asthma in Pediatric Patients With Asthma

Further study details as provided by Amphastar Pharmaceuitcals, Inc.:

Primary Outcome Measures:

The primary endpoint for efficacy evaluation is to obtain the ratio of the geometric mean of area under the curve of change in FEV1%versus time for pediatric patients using the study drug to the active reference drug. [ Time Frame: visits 1 and 3 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

AUC of serial FEV1 volume changes from the Same Day Baseline versus time, during the 6-hr post-dose. [ Time Frame: each visit ] [ Designated as safety issue: No ]
Time to onset of bronchodilator effect, determined by linear interpolation as the time point when FEV1 first exceeded 12.0% over the respective Same Day Baseline. [ Time Frame: each visist ] [ Designated as safety issue: No ]
The peak bronchodilator response, Fmax, defined as the maximum FEV1 (% change from the Same Day Baseline). [ Time Frame: each visit ] [ Designated as safety issue: No ]
The time to peak bronchodilator response (FEV1), with Fmax defined as the maximum FEV1 (% change from the Same Day Baseline). [ Time Frame: each visit ] [ Designated as safety issue: No ]
Duration of bronchodilator effect, defined as the total duration when FEV1 is maintained greater than or equal to 12.0% above the respective Same Day Baseline values. [ Time Frame: each visit ] [ Designated as safety issue: No ]
(6) Percentage of positive responders including those whose FEV1 exceed the Same-Day Baseline by greater than or equal to 12.0% at or before 30 min post-dose (quick responders), and at any time during the entire 6 hr post-dose (overall responders). [ Time Frame: each visit ] [ Designated as safety issue: No ]
Pharmacokinetic parameters including Cmax, AUC, and t1/2, based on a population pharmacokinetic (PPK) approach with sparse blood samples, conducted at Clinical Visit 3. [ Time Frame: visit 3 ] [ Designated as safety issue: No ]
Requirements for rescue/concomitant medications, for each treatment group [ Time Frame: end of study ] [ Designated as safety issue: No ]
Mean Overall Asthma Control Scores evaluated by investigators [ Time Frame: end of study ] [ Designated as safety issue: No ]
Total daytime asthma symptom scores [ Time Frame: end of study ] [ Designated as safety issue: No ]
Nighttime sleep disturbance scores [ Time Frame: end of study ] [ Designated as safety issue: No ]
Morning and evening pre-dose Peak Expiratory Flow Rate (PEF). [ Time Frame: end of study ] [ Designated as safety issue: No ]
Number of asthma exacerbations during the entire study period [ Time Frame: end of study ] [ Designated as safety issue: No ]
Vital signs (SBP/DBP, and heart rate) will be monitored at: 1. baseline (prior to dosing), and; 2. 60 minutes post-dose, but before the 60 min FEV1 tests. 3. 360 minutes post-dose, but before the 360 min FEV1 tests. [ Time Frame: Screening, visits 1 and 3 ] [ Designated as safety issue: Yes ]
A 12-lead ECG (HR, QT and QTc intervals) recorded at: 1. pre-dose, and; 2. 60 minutes post-dose, but before the 60 min FEV1 tests. [ Time Frame: Screening and visits 1 and 3 ] [ Designated as safety issue: Yes ]
lab tests for CBC, blood metabolic panel, and urinalysis. [ Time Frame: Pre-study and end of study ] [ Designated as safety issue: Yes ]
Physical examinations [ Time Frame: Screening and end of study ] [ Designated as safety issue: Yes ]
Blood potassium levels [ Time Frame: Screening and EOS for all subjects; and at 120+15 min post dose (Visit 3) for population PK subjects only ] [ Designated as safety issue: Yes ]
Study compliance and safety will be reviewed. Concomitant medications will be reviewed and recorded [ Time Frame: All Study Visits ] [ Designated as safety issue: Yes ]
Adverse events, whether observed by investigators or reported by subjects, will be documented and followed up if deemed necessary. [ Time Frame: At All Study Visits ] [ Designated as safety issue: Yes ]

Enrollment:	48
Study Start Date:	March 2008
Study Completion Date:	November 2008
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
T: Experimental Armstrong Albuterol Sulfate Inhalation Aerosol, 216 mcg albuterol sulfate (108 mcg/actuation) is equivalent to 180 mcg albuterol base (90 mcg/actuation).	Drug: Armstrong Albuterol Sulfate Inhalation Aerosol Albuterol Sulfate Inhalation Aerosol, 216 mcg albuterol sulfate (108 mcg/actuation) is equivalent to 180 mcg albuterol base (90 mcg/actuation).
R: Active Comparator Proventil-HFA, Albuterol Sulfate Inhalation Aerosol, 216 mcg albuterol sulfate (108 mcg/actuation) is equivalent to 180 mcg albuterol base (90 mcg/actuation).	Drug: Albuterol Sulfate Inhalation Aerosol Albuterol Sulfate Inhalation Aerosol, 216 mcg albuterol sulfate (108 mcg/actuation) is equivalent to 180 mcg albuterol base (90 mcg/actuation).

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Eligibility

Ages Eligible for Study:	4 Years to 11 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Generally healthy.
Male and female mild-to-moderate asthma patients.
Aged 4 - 11 yr (upon screening).
Female patients must be premenarchal upon Visit-1, and those who become menarchal during the study must use an accepted method of contraception including abstinence.
A documented history of asthma, for at-least 6-months prior to Screening, requiring inhaled B-adrenergic agonists, with or without inhaled corticosteroids for asthma symptom control.
Satisfying asthma stability criterion, defined as no changes in asthma therapy and no asthma-related hospitalization or emergency room visits, over the 4 weeks prior to Screening.
Being able to withhold treatment with inhaled bronchodilators and/or restricted medications for the minimum washout periods indicated in Appendix II, for the purpose of conducting clinical visits.
Having a baseline forced expiratory volume in 1 second (FEV1), that is 50.0-100.0% of predicted values at the screening (Screening Baseline FEV1).
Demonstrating a greater than or equal to 12.0% reversibility in the Reversibility Test, at 30 min after inhaling 2-4 puffs (180-360 mcg) of Ventolin-HFA.
Demonstrating correct use of metered-dose inhaler (MDIs), and acceptable performance in the FEV1 measurements.
Has properly consented, with a parent or a legal guardian, to participate in this study.

Exclusion Criteria:

Any current or past significant medical conditions that, according to the investigator, might affect pharmacodynamic response to the study drugs, such as significant systemic or respiratory diseases (e.g., cystic fibrosis, bronchiectasis, emphysema, nonreversible pulmonary diseases), other than asthma.
Concurrent clinically significant cardiovascular, hematological, renal, neurological, hepatic, and endocrine disorders, or psychiatric diseases.
Known intolerance or hypersensitivity to any component of the MDI formulation (e.g., albuterol, HFA-134a, oleic acid, ethanol).
Recent upper (within 2 weeks) or lower (within 4 weeks) respiratory tract infection before screening.
Recent (within 4 weeks) use of systemic (or oral) corticosteroids and B-adrenergic bronchodilators; or recent (within 2 weeks) use of monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), or B-blockers; before the Screening.
Having been on other investigational drug/device studies in the last 30 days prior to screening.
Known or reasonably suspected alcohol/drug abuses.
Having smoked within the last 12 months.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00634517

Locations

United States, California
West Coast Clinical Trials Phase 2-4, LLC
Long Beach, California, United States, 90806
Bensch Research Associates
Stockton, California, United States, 95207
Allergy Associates Medical Group, Inc.
San Diego, California, United States, 92120
United States, Oregon
Clinical Research Institute of Southern Oregon
Medford, Oregon, United States, 97504
Integrated Medical Research
Ashland, Oregon, United States, 97520
Allergy and Asthma Research Group
Eugene, Oregon, United States, 97401
Allergy Associates Research Center
Portland, Oregon, United States, 97213
United States, Texas
Pharmaceutical Research & Consulting, Inc.
Dallas, Texas, United States, 75231

Sponsors and Collaborators

Amphastar Pharmaceuitcals, Inc.

More Information

No publications provided

Responsible Party:	Amphastar Pharmaceuticals, Inc. ( Jim Shi, MD, PhD, Medical Director )
Study ID Numbers:	API-A004-CLN-E
Study First Received:	March 7, 2008
Last Updated:	December 17, 2008
ClinicalTrials.gov Identifier:	NCT00634517 History of Changes
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Neurotransmitter Agents
Adrenergic beta-Agonists
Bronchial Diseases
Adrenergic Agents
Albuterol
Asthma
Anti-Asthmatic Agents
Adrenergic Agonists

Lung Diseases, Obstructive
Hypersensitivity
Respiratory Tract Diseases
Lung Diseases
Hypersensitivity, Immediate
Peripheral Nervous System Agents
Bronchodilator Agents
Respiratory Hypersensitivity

Additional relevant MeSH terms:

Respiratory System Agents
Neurotransmitter Agents
Bronchial Diseases
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Albuterol
Physiological Effects of Drugs
Reproductive Control Agents
Adrenergic Agonists
Hypersensitivity
Lung Diseases, Obstructive
Respiratory Tract Diseases
Tocolytic Agents

Therapeutic Uses
Immune System Diseases
Adrenergic beta-Agonists
Asthma
Anti-Asthmatic Agents
Pharmacologic Actions
Autonomic Agents
Lung Diseases
Hypersensitivity, Immediate
Peripheral Nervous System Agents
Bronchodilator Agents
Respiratory Hypersensitivity

ClinicalTrials.gov processed this record on May 07, 2009