Controlled, 12-Week Study of Albuterol HFA Versus the Active Control, Proventil(R)-HFA in Asthmatic Patients
Information source: Amphastar Pharmaceuticals, Inc.
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Asthma
Intervention: albuterol HFA (Armstrong's) (Drug); albuterol HFA (Proventil HFA) (Drug); HFA placebo (Drug)
Phase: Phase 3
Status: Terminated
Sponsored by: Amphastar Pharmaceuticals, Inc.
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).
Clinical Details
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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: 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.
Secondary outcome: The comparative analysis of AUC of FEV1 (% change from the Same-Day Baseline) versus time, for bronchodilator effect (between Albuterol-HFA and Proventil-HFA).AUC of FEV1-time curve (changes of actual volumes from the Same-Day Baseline). Time to onset of bronchodilator effect, determined by linear interpolation as the time point where FEV1 first reaches 12% over Same-Day Baseline. The peak bronchodilator response, defined as the maximum FEV1 (% change from Same-Day Baseline) post-dose. The time to peak FEV1 effect, measured as the time point of peak response, as defined (4) above. 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). 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). Number of inhalations of the rescue inhalers taken. Global assessment of Overall Asthma Control Scores by investigators. Total daytime asthma symptom scores. Nighttime sleep disturbance scores. Morning pre-dose Peak Expiratory Flow Rate (PEF). 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. The in vitro performance of the Albuterol-HFA MDI will be evaluated. 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. 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). Data for CBC, blood chemistry panel (8-hr fasted), and urinalysis. Study compliance and diaries will be reviewed Concomitant medications will be reviewed and recorded Adverse events/side effects whether observed by investigators or reported by subjects, will be documented, evaluated, followed up, and treated if deemed necessary.
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
Minimum age: 12 Years.
Maximum age: 75 Years.
Gender(s): Both.
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.
Locations and Contacts
Pulmonary Associates of Mobile, PC, Mobile, Alabama 36608, United States
Allergy & Asthma Specialists Medical Group, Huntington Beach, California 92647, United States
Allergy & Asthma Care Center, Long Beach, California 90808, United States
Allergy Asthma & Respiratory Care Medical Center, Long Beach, California 90806, United States
Southern California Research, Mission Viejo, California 92691, United States
CHOC PSF, AMC, Divison AA and I, Orange, California 92868, United States
Clinical Trials of Orange County, Orange, California 92868, United States
Peninsula Research Associates, Rolling Hills Estates, California 90274, United States
Allergy Associates Medical Group, San Diego, California 92120, United States
Allergy & Asthma Associates of Santa Clara Valley Research Centere, San Jose, California 95117, United States
Bensch Research Associates, Stockton, California 95207, United States
Colorado Allergy and Asthma Centers, Denver, Colorado 80230, United States
Colorado Allergy and Asthma Centers, Lakewood, Colorado 80401, United States
Rocky Mountain center for Clinical Research, Wheatridge, Colorado 80033, United States
Waterbury Pulmonary Research, Waterbury, Connecticut 06708, United States
Allergy and Asthma Care of Florida, Ocala, Florida 34471, United States
Brandon-Valrico Center for Allergy and Astham Research,LLC, Valrico, Florida 33594, United States
Atlanta Allergy and Asthma Clinic, Woodstock, Georgia 30188, United States
Family Allergy and Asthma Research Institute, Louisville, Kentucky 40215, United States
Northeast Medical Research Group, N. Dartmouth, Massachusetts 02747, United States
Park Nicollet Institute, Minneapolis, Minnesota 55416, United States
MEDEX Healthcare Research, Inc., St. Louis, Missouri 63117, United States
The Clinical Research Center, LLC, St. Louis, Missouri 63141, United States
Clinical Research Group of Montana, Bozeman, Montana 59718, United States
Montant Medical Research, Missoula, Montana 59808, United States
Asthma and Allergy Center, PC, Papillion, Nebraska 68046, United States
New Horizons Clinical Research, Cincinnati, Ohio 45242, United States
Toledo Center for Clinical Research, Sylvania, Ohio 43560, United States
Integrated Medical Research, Ashland, Oregon 97520, United States
Allergy & Asthma Research Group, Eugene, Oregon 97504, United States
Allergy Asthma and Dermatology Research, Lake Oswego, Oregon 97035, United States
Clinical Research Institute of Southern Oregon, Medford, Oregon 97504, United States
Allergy Associates Research Center, Portland, Oregon 97213, United States
Allergy and Clinical Immunology Associates, Pittsburgh, Pennsylvania 15241, United States
Pharmaceutical Research & Consulting, Inc., Dallas, Texas 25231, United States
Allergy and Asthma Associates of Houston, Houston, Texas 77054, United States
Clinical Trials of North Houston, Houston, Texas 77070, United States
Kerrville Allergy and Asthma Associates, Kerrville, Texas 78028, United States
Biogenics Research Institute, San Antonio, Texas 78229, United States
Sylvania Research Associates, San Antonio, Texas 78229, United States
Virginia Adult and Pediatric Allergy and Asthma, PC, Richmond, Virginia 23229, United States
Asthma, Inc., Seattle, Washington 98105, United States
Additional Information
Starting date: September 2007
Last updated: July 11, 2013
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