Controlled, 12-Week Study of Albuterol HFA Versus the Active Control, Proventil(R)-HFA in Asthmatic Patients

Asthma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00635505
• Other study ID #: API-A004-CLN-C
• Status: Terminated
• Phase: Phase 3
• First received: March 7, 2008
• Last updated: July 11, 2013
• Start date: September 2007
• Est. completion date: August 2008

Study information

• Verified date: July 2012
• Source: Amphastar Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 300
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• albuterol HFA (Armstrong's)
180 mcg QID 12 weeks
• albuterol HFA (Proventil HFA)
180 mcg QID 12 weeks
• HFA placebo
2 actuations QID 12 weeks or until use of rescue drug

Locations

Country	Name	City	State
United States	Integrated Medical Research	Ashland	Oregon
United States	Clinical Research Group of Montana	Bozeman	Montana
United States	New Horizons Clinical Research	Cincinnati	Ohio
United States	Pharmaceutical Research & Consulting, Inc.	Dallas	Texas
United States	Colorado Allergy and Asthma Centers	Denver	Colorado
United States	Allergy & Asthma Research Group	Eugene	Oregon
United States	Allergy and Asthma Associates of Houston	Houston	Texas
United States	Clinical Trials of North Houston	Houston	Texas
United States	Allergy & Asthma Specialists Medical Group	Huntington Beach	California
United States	Kerrville Allergy and Asthma Associates	Kerrville	Texas
United States	Allergy Asthma and Dermatology Research	Lake Oswego	Oregon
United States	Colorado Allergy and Asthma Centers	Lakewood	Colorado
United States	Allergy & Asthma Care Center	Long Beach	California
United States	Allergy Asthma & Respiratory Care Medical Center	Long Beach	California
United States	Family Allergy and Asthma Research Institute	Louisville	Kentucky
United States	Clinical Research Institute of Southern Oregon	Medford	Oregon
United States	Park Nicollet Institute	Minneapolis	Minnesota
United States	Southern California Research	Mission Viejo	California
United States	Montant Medical Research	Missoula	Montana
United States	Pulmonary Associates of Mobile, PC	Mobile	Alabama
United States	Northeast Medical Research Group	N. Dartmouth	Massachusetts
United States	Allergy and Asthma Care of Florida	Ocala	Florida
United States	CHOC PSF, AMC, Divison AA and I	Orange	California
United States	Clinical Trials of Orange County	Orange	California
United States	Asthma and Allergy Center, PC	Papillion	Nebraska
United States	Allergy and Clinical Immunology Associates	Pittsburgh	Pennsylvania
United States	Allergy Associates Research Center	Portland	Oregon
United States	Virginia Adult and Pediatric Allergy and Asthma, PC	Richmond	Virginia
United States	Peninsula Research Associates	Rolling Hills Estates	California
United States	Biogenics Research Institute	San Antonio	Texas
United States	Sylvania Research Associates	San Antonio	Texas
United States	Allergy Associates Medical Group	San Diego	California
United States	Allergy & Asthma Associates of Santa Clara Valley Research Centere	San Jose	California
United States	Asthma, Inc.	Seattle	Washington
United States	MEDEX Healthcare Research, Inc.	St. Louis	Missouri
United States	The Clinical Research Center, LLC	St. Louis	Missouri
United States	Bensch Research Associates	Stockton	California
United States	Toledo Center for Clinical Research	Sylvania	Ohio
United States	Brandon-Valrico Center for Allergy and Astham Research,LLC	Valrico	Florida
United States	Waterbury Pulmonary Research	Waterbury	Connecticut
United States	Rocky Mountain center for Clinical Research	Wheatridge	Colorado
United States	Atlanta Allergy and Asthma Clinic	Woodstock	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Amphastar Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		Concurent with each visit	No
Secondary	The comparative analysis of AUC of FEV1 (% change from the Same-Day Baseline) versus time, for bronchodilator effect (between Albuterol-HFA and Proventil-HFA).		End of Study	No
Secondary	AUC of FEV1-time curve (changes of actual volumes from the Same-Day Baseline).		End of Study	No
Secondary	Time to onset of bronchodilator effect, determined by linear interpolation as the time point where FEV1 first reaches 12% over Same-Day Baseline.		End of Study	No
Secondary	The peak bronchodilator response, defined as the maximum FEV1 (% change from Same-Day Baseline) post-dose.		end of study	No
Secondary	The time to peak FEV1 effect, measured as the time point of peak response, as defined (4) above.		End of Study	No
Secondary	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).		Concurrent with each visit	No
Secondary	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).		Concurrent with visit	No
Secondary	Number of inhalations of the rescue inhalers taken.		Concurrent with each visit	No
Secondary	Global assessment of Overall Asthma Control Scores by investigators.		End of Study	No
Secondary	Total daytime asthma symptom scores.		End of Study	No
Secondary	Nighttime sleep disturbance scores.		End of Study	No
Secondary	Morning pre-dose Peak Expiratory Flow Rate (PEF).		Concurrent with each visit	No
Secondary	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.		End of Study	No
Secondary	The in vitro performance of the Albuterol-HFA MDI will be evaluated.		Concurrent with each visit	No
Secondary	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.		concurrent with study visits as noted	Yes
Secondary	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).		Clinical Visits 1 and 5	Yes
Secondary	Data for CBC, blood chemistry panel (8-hr fasted), and urinalysis.		Screening and end-of-study	Yes
Secondary	Study compliance and diaries will be reviewed		at all cliniical visits	Yes
Secondary	Concomitant medications will be reviewed and recorded		each study visit	Yes
Secondary	Adverse events/side effects whether observed by investigators or reported by subjects, will be documented, evaluated, followed up, and treated if deemed necessary.		concurrent with each study visit	Yes