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

Sponsor:	Amphastar Pharmaceuticals, Inc.
Information provided by (Responsible Party):	Amphastar Pharmaceuticals, 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

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:	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

Resource links provided by NLM:

MedlinePlus related topics: Asthma Potassium

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

U.S. FDA Resources

Further study details as provided by Amphastar Pharmaceuticals, 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
Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: T 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). Other Name: Albuterol HFA
Active Comparator: R 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). Other Name: Proventil-HFA

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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
Allergy Associates Medical Group, Inc.
San Diego, California, United States, 92120
Bensch Research Associates
Stockton, California, United States, 95207
United States, Oregon
Integrated Medical Research
Ashland, Oregon, United States, 97520
Allergy and Asthma Research Group
Eugene, Oregon, United States, 97401
Clinical Research Institute of Southern Oregon
Medford, Oregon, United States, 97504
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 Pharmaceuticals, Inc.

More Information

No publications provided

Responsible Party:	Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00634517 History of Changes
Other Study ID Numbers:	API-A004-CLN-E
Study First Received:	March 7, 2008
Last Updated:	January 23, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Albuterol
Tocolytic Agents
Reproductive Control Agents
Physiological Effects of Drugs

Pharmacologic Actions
Therapeutic Uses
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on February 12, 2012