Clinical trial NCT00635505: Controlled, 12-Week Study of Albuterol HFA Versus the Active Control, Proventil(R)-HFA in Asthmatic Patients
Official title: Randomized, Placebo-Controlled, Parallel, Multi-Center, 12-Week Study to Evaluate the Efficacy and Safety of Albuterol HFA Versus the Active Control, Proventil(R)-HFA in Adult and Adolescent Asthmatic Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Asthma
Keywords: Asthma
albuterol
HFA
Lead sponsor: Amphastar Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2008-03-13
Enrollment: 300
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This 12-week clinical study evaluates the safety and efficacy of Albuterol Sulfate HFA Inhalation Aerosol (Albuterol-HFA, or: A004), Armstrong's proposed HFA formulation of metered dose inhaler (MDI) of Albuterol (Treatment T), in comparison with:

1. Placebo control: (HFA propellant only, Treatment P); and
2. Active control: 3M/Key's Proventil-HFA (Treatment R).

The treatments will be given as self-administered oral inhalations in adult and adolescent patients with mild-to-moderate asthma, for 12-weeks. Dosing regimen throughout the 12-week study is two actuations four times daily (QID).

Detailed description: This is a randomized, parallel, multicenter, 12-week study in adolescent and adult patients with mild-to-moderate asthma, to evaluate the efficacy and safety of Armstrong's Albuterol-HFA MDI, in comparison to a Placebo Control and an Active Control of Proventil-HFA. While Albuterol-HFA (Treatment T) and Placebo (Treatment P) will be double-blinded to both the subjects and investigational staff, the active comparator drug, Proventil-HFA (Treatment R), can only be evaluator-blinded, due to: (1) its physical appearance differing from that of the T and P devices; and (2) unavailability of a Proventil-HFA placebo which would otherwise be used for a double-dummy design. All study medications will have the canisters and all product-identifying text or graphics (e.g., molded text on actuator) masked so that the treatments cannot be identified. No subject in any study arm will be given any information that could reveal the nature of the treatment given. All study subjects will be instructed not to reveal or discuss the study medications to the study staff or other subjects. The designated study evaluator(s), who conduct the clinical visits and safety and efficacy evaluations and perform the data recording and transcription, will be blinded to the study medications.

All subjects will be screened for enrollment, and will be randomized into the following three treatment groups in a double-blinded (for Treatments T and P) or evaluator-blinded (for Treatment R) manner:

Treatment T (Albuterol-HFA, N=200): 216 mcg albuterol sulfate (equivalent to 180 mcg albuterol base), QID; Treatment R (Proventil-HFA, N=50): 216 mcg albuterol sulfate (equivalent to 180 mcg albuterol base), QID; Treatment P (Placebo-HFA, N=50): two actuations of placebo, QID.

Randomization is achieved with blocks of six (6), with four (4) patients receiving Albuterol-HFA for every one (1) patient receiving Proventil-HFA and every one (1) receiving the Placebo-HFA. At each Clinical Visit that takes place every 3 weeks, the double-blinded (T, P) or evaluator-blinded (R) study drugs will be distributed in resealable masking pouches to the subjects of each arm.

An additional aim of the study is to evaluate the effect of weekly cleaning on the Albuterol-HFA MDI device clinical performance throughout the four, 3-week life-of-device treatment cycles, in conformance with the FDA's specific requirements.

Arms:

All subjects will be screened for enrollment, and will be randomized into the following three treatment groups in a double-blinded (for Treatments T and P) or evaluator-blinded (for Treatment R) manner:

Treatment T (Albuterol-HFA, N=200): 216 mcg albuterol sulfate (equivalent to 180 mcg albuterol base), QID; Treatment R (Proventil-HFA, N=50): 216 mcg albuterol sulfate (equivalent to 180 mcg albuterol base), QID; Treatment P (Placebo-HFA, N=50): two actuations of placebo, QID.

Eligibility criteria: Inclusion Criteria:

* Male and female asthma patients aged 12 - 75 years, in general good health.
* A documented history of mild to moderate asthma, for at-least 6-months prior to Screening, requiring inhaled B2-adrenergic agonists, with or without orally inhaled corticosteroids, for asthma treatment.
* Satisfying criteria of asthma stability, defined as no asthma-related hospitalization or emergency visits, and no significant changes in asthma therapy, over 4 weeks prior to Screening (with exception for switching from long- to short-acting B2-agonists).
* Can tolerate withholding treatment with inhaled bronchodilators and other allowed medications for the minimum washout periods indicated in Appendix II prior to the Screening Baseline FEV1 testing.
* Having a Screening Baseline FEV1 test that falls within 50-90% of the predicted values.
* Airway Reversibility PFT at screening should demonstrate a greater than 12% increase in FEV1 at 30 minutes of inhaling 2 actuations of Ventolin-HFA (180 mcg albuterol base).
* Demonstrating satisfactory techniques in the use of metered-dose inhaler (MDIs) and a hand held peak flow meter.
* Female patients of child-bearing potential being non-pregnant and non-lactating at Screening and throughout the study, and using an acceptable method of contraception during the study.
* Has properly consented to participate in this study.

Exclusion Criteria:

* Male and female asthma patients aged 12 - 75 years, in general good health.
* A documented history of mild to moderate asthma, for at-least 6-months prior to Screening, requiring inhaled B2-adrenergic agonists, with or without orally inhaled corticosteroids, for asthma treatment.
* Satisfying criteria of asthma stability, defined as no asthma-related hospitalization or emergency visits, and no significant changes in asthma therapy, over 4 weeks prior to Screening (with exception for switching from long- to short-acting B2-agonists).
* Can tolerate withholding treatment with inhaled bronchodilators and other allowed medications for the minimum washout periods indicated in Appendix II prior to the Screening Baseline FEV1 testing.
* Having a Screening Baseline FEV1 test that falls within 50-90% of the predicted values.
* Airway Reversibility PFT at screening should demonstrate a greater than12% increase in FEV1 at 30 minutes of inhaling 2 actuations of Ventolin-HFA (180 mcg albuterol base).
* Demonstrating satisfactory techniques in the use of metered-dose inhaler (MDIs) and a hand held peak flow meter.
* Female patients of child-bearing potential being non-pregnant and non-lactating at Screening and throughout the study, and using an acceptable method of contraception during the study.
* Has properly consented to participate in this study.

Primary outcomes:
measure: The primary endpoint is the bronchodilator effect expressed as the mean area under the curve (AUC) of FEV1 (% change from Same-Day Baseline FEV1) versus time.
timeFrame: Concurent with each visit
Secondary outcomes:
measure: The comparative analysis of AUC of FEV1 (% change from the Same-Day Baseline) versus time, for bronchodilator effect (between Albuterol-HFA and Proventil-HFA).
timeFrame: End of Study
measure: AUC of FEV1-time curve (changes of actual volumes from the Same-Day Baseline).
timeFrame: End of Study
measure: Time to onset of bronchodilator effect, determined by linear interpolation as the time point where FEV1 first reaches 12% over Same-Day Baseline.
timeFrame: End of Study
measure: The peak bronchodilator response, defined as the maximum FEV1 (% change from Same-Day Baseline) post-dose.
timeFrame: end of study
measure: The time to peak FEV1 effect, measured as the time point of peak response, as defined (4) above.
timeFrame: End of Study
measure: Duration of bronchodilator effect, defined as the total length of time when FEV1 is maintained 12% above the respective Same-Day Baseline values (time points calculated with linear interpolation).
timeFrame: Concurrent with each visit
measure: Percentage of positive responders including those whose FEV1 exceed the Same-Day Baseline by 12% within 30 minutes post-dose (quick responders), and during the entire 6 hr post-dose (overall responders).
timeFrame: Concurrent with visit
measure: Number of inhalations of the rescue inhalers taken.
timeFrame: Concurrent with each visit
measure: Global assessment of Overall Asthma Control Scores by investigators.
timeFrame: End of Study
measure: Total daytime asthma symptom scores.
timeFrame: End of Study
measure: Nighttime sleep disturbance scores.
timeFrame: End of Study
measure: Morning pre-dose Peak Expiratory Flow Rate (PEF).
timeFrame: Concurrent with each visit
measure: The clinical performances of the Albuterol-HFA MDI at the representative first, middle and last one third of the usable life stage, are compared with each other, and are also compared to those of the active control, Proventil-HFA.
timeFrame: End of Study
measure: The in vitro performance of the Albuterol-HFA MDI will be evaluated.
timeFrame: Concurrent with each visit
measure: Vital signs (SBP/DBP, and heart rate) will be monitored at Clinical Visit 1, 3 and 5, at baseline (within 30 minutes prior to dosing), and 90+/-15 min, and 360+/-30 min, post-dose.
timeFrame: concurrent with study visits as noted
measure: A 12-lead ECG (for HR, QT and QTc intervals) will be recorded at Screening Visit, and at baseline (within 30 min) pre-dose and at 90+/-15 min post-dose (predicted time of peak effect).
timeFrame: Clinical Visits 1 and 5
measure: Data for CBC, blood chemistry panel (8-hr fasted), and urinalysis.
timeFrame: Screening and end-of-study
measure: Study compliance and diaries will be reviewed
timeFrame: at all cliniical visits
measure: Concomitant medications will be reviewed and recorded
timeFrame: each study visit
measure: Adverse events/side effects whether observed by investigators or reported by subjects, will be documented, evaluated, followed up, and treated if deemed necessary.
timeFrame: concurrent with each study visit
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Pulmonary Associates of Mobile, PC
state: Alabama
city: Huntington Beach
country: United States
facility: Allergy & Asthma Specialists Medical Group
state: California
city: Long Beach
country: United States
facility: Allergy Asthma & Respiratory Care Medical Center
state: California
city: Long Beach
country: United States
facility: Allergy & Asthma Care Center
state: California
city: Mission Viejo
country: United States
facility: Southern California Research
state: California
city: Orange
country: United States
facility: CHOC PSF, AMC, Divison AA and I
state: California
city: Orange
country: United States
facility: Clinical Trials of Orange County
state: California
city: Rolling Hills Estates
country: United States
facility: Peninsula Research Associates
state: California
city: San Diego
country: United States
facility: Allergy Associates Medical Group
state: California
city: San Jose
country: United States
facility: Allergy & Asthma Associates of Santa Clara Valley Research Centere
state: California
city: Stockton
country: United States
facility: Bensch Research Associates
state: California
city: Denver
country: United States
facility: Colorado Allergy and Asthma Centers
state: Colorado
city: Lakewood
country: United States
facility: Colorado Allergy and Asthma Centers
state: Colorado
city: Wheatridge
country: United States
facility: Rocky Mountain center for Clinical Research
state: Colorado
city: Waterbury
country: United States
facility: Waterbury Pulmonary Research
state: Connecticut
city: Ocala
country: United States
facility: Allergy and Asthma Care of Florida
state: Florida
city: Valrico
country: United States
facility: Brandon-Valrico Center for Allergy and Astham Research,LLC
state: Florida
city: Woodstock
country: United States
facility: Atlanta Allergy and Asthma Clinic
state: Georgia
city: Louisville
country: United States
facility: Family Allergy and Asthma Research Institute
state: Kentucky
city: N. Dartmouth
country: United States
facility: Northeast Medical Research Group
state: Massachusetts
city: Minneapolis
country: United States
facility: Park Nicollet Institute
state: Minnesota
city: St. Louis
country: United States
facility: MEDEX Healthcare Research, Inc.
state: Missouri
city: St. Louis
country: United States
facility: The Clinical Research Center, LLC
state: Missouri
city: Bozeman
country: United States
facility: Clinical Research Group of Montana
state: Montana
city: Missoula
country: United States
facility: Montant Medical Research
state: Montana
city: Papillion
country: United States
facility: Asthma and Allergy Center, PC
state: Nebraska
city: Cincinnati
country: United States
facility: New Horizons Clinical Research
state: Ohio
city: Sylvania
country: United States
facility: Toledo Center for Clinical Research
state: Ohio
city: Ashland
country: United States
facility: Integrated Medical Research
state: Oregon
city: Eugene
country: United States
facility: Allergy & Asthma Research Group
state: Oregon
city: Lake Oswego
country: United States
facility: Allergy Asthma and Dermatology Research
state: Oregon
city: Medford
country: United States
facility: Clinical Research Institute of Southern Oregon
state: Oregon
city: Portland
country: United States
facility: Allergy Associates Research Center
state: Oregon
city: Pittsburgh
country: United States
facility: Allergy and Clinical Immunology Associates
state: Pennsylvania
city: Dallas
country: United States
facility: Pharmaceutical Research & Consulting, Inc.
state: Texas
city: Houston
country: United States
facility: Allergy and Asthma Associates of Houston
state: Texas
city: Houston
country: United States
facility: Clinical Trials of North Houston
state: Texas
city: Kerrville
country: United States
facility: Kerrville Allergy and Asthma Associates
state: Texas
city: San Antonio
country: United States
facility: Biogenics Research Institute
state: Texas
city: San Antonio
country: United States
facility: Sylvania Research Associates
state: Texas
city: Richmond
country: United States
facility: Virginia Adult and Pediatric Allergy and Asthma, PC
state: Virginia
city: Seattle
country: United States
facility: Asthma, Inc.
state: Washington
Study officials:
References: