Randomized, Placebo-controlled Study Comparing Efficacy of Fluticasone/Salmeterol Combination to Advair in Asthmatics

Study Overview
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Brief Summary
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This is a pivotal trial that will examine therapeutic equivalence (BE) of a new generic fixed-dose combination product containing fluticasone propionate 100 mcg / salmeterol 50 mcg (as xinafoate salt) and reference listed drug (RLD) Advair® Diskus 100/50 in adult patients with chronic but stable asthma as defined in the National Asthma Education and Prevention Program Expert Panel Report 3 (NAEPP 3) guidelines

Detailed Description
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This pivotal trial will examine therapeutic equivalence of a new generic fixed-dose combination product containing fluticasone propionate 100 mcg / salmeterol 50 mcg (as xinafoate salt) and reference listed drug (RLD) Advair® Diskus 100/50 in adult patients with chronic but stable asthma as defined in National Asthma Education and Prevention Program Expert Panel Report 3 (NAEPP 3) guidelines [2]. To ensure adequate study sensitivity the test and reference products should both be statistically superior to placebo (p<0.05) with regard to the BE study primary endpoints. A secondary study objective is the safety and tolerability of the test compound.

Official Title
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Randomized, Parallel, Placebo-controlled, Multiple Dose, Multicenter Study to Compare the Efficacy of Fluticasone/Salmeterol (Test) to Advair® Diskus (GSK) in Adult Asthma Patients

Conditions
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Asthma

Intervention / Treatment
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* Drug: Fluticasone propionate 100 mcg / salmeterol 50 mcg
* Drug: Generic fluticasone propionate 100 mcg / salmeterol 50 mcg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male or female subjects of non-childbearing or of childbearing potential committed to consistent and correct use of an acceptable method of birth control Diagnosed with asthma, as defined by the National Asthma Education and Prevention Program (NAEPP),5 at least 6 months prior to screening Moderate-to-severe asthma with a pre-bronchodilator FEV1 of >45% and <85% of predicted normal, measured at least 6 hours after short-acting β agonist (SABA)and at least 24 hours after the last dose of long-acting β agonist (LABA), at the screening visit and on the day of treatment >15% and >0.20 L reversibility of FEV1 within 30 minutes following 360 mcg of albuterol inhalation (pMDI) Patients should be stable on their chronic asthma treatment regimen for at least 4 weeks prior to enrollment Currently non-smoking; having not used tobacco products (i.e., cigarettes, cigars, pipe tobacco) within the past year, and having < 10 pack-years of historical use Able to replace current regularly scheduled short-acting β agonists (SABAs) with salbutamol/albuterol inhaler for use only on an as-needed basis for the duration of the study (subjects should be able to withhold all inhaled SABAs for at least 6 hours prior to lung function assessments on study visits) Willing to discontinue their asthma medications (inhaled corticosteroids and long-acting β agonists) during the run-in period and for the remainder of the study Willingness to give their written informed consent to participate in the study Exclusion Criteria: Life-threatening asthma, defined as a history of asthma episodes(s) requiring intubation, and/or associated with hypercapnia, respiratory arrest or hypoxic seizures, asthma-related syncopal episodes(s), or hospitalizations within the past year or during the run-in period Significant respiratory disease other than asthma (chronic obstructive pulmonary disease (COPD), interstitial lung disease, etc.) Evidence or history of clinically significant disease or abnormality including congestive heart failure, uncontrolled hypertension, uncontrolled coronary artery disease, myocardial infarction, or cardiac dysrhythmia. In addition,historical or current evidence of significant hematologic, hepatic, neurologic, psychiatric, renal, or other diseases that, in the opinion of the investigator, would put the patient at risk through study participation, or would affect the study analyses if the disease exacerbated during the study Patients who required systemic corticosteroids (for any reason) within the past 4 weeks Hypersensitivity to any sympathomimetic drug (e.g., formoterol or albuterol) or any inhaled, intranasal, or systemic corticosteroid therapy Patients currently receiving β-blockers

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment 1<br>Generic fluticasone propionate 100 mcg / salmeterol 50 mcg. Single puff, twice daily (approximately every 12 hr) for 4 weeks | Drug: Generic fluticasone propionate 100 mcg / salmeterol 50 mcg<br>* Generic inhaler containing pMDI containing fluticasone and salmeterol<br>* Other names: Generic Test;|
| Experimental: Treatment 2<br>Advair 100/50 Diskus pMDI containing fluticasone propionate 100mcg / salmeterol 50 mcg. Single puff, twice daily (approximately every 12 hr) for 4 weeks | Drug: Fluticasone propionate 100 mcg / salmeterol 50 mcg<br>* Brand inhaler containing pMDI containing fluticasone and salmeterol<br>* Other names: Advair;|
| Placebo Comparator: Treatment 3<br>Placebo inhalation. Single puff, twice daily (approximately every 12 hr) for 4 weeks | Drug: Placebo<br>* Placebo inhaler<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline-corrected area under the serial Forced Expiratory Volume in the first second (FEV1)-time effect curve calculated from time zero to 12 hours on the first day of the treatment | Baseline-corrected area under the serial FEV1-time effect curve calculated from time zero to 12 hours on the first day of the treatment (Visit 2, Day 1) to assess equivalence of test drug with reference listed drug (RLD) Advair® Diskus® 100/50, and to assess superiority over placebo | up to 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Forced Vital Capacity (FVC) results at the times of FEV1 measurements |  | Day 1 and Day 28 | 
| Daily rescue medication used | The type and frequency of rescue medication used | 8 weeks | 
| Number and type of adverse events |  | 8 weeks |