MGR001 / Advair Diskus Local Equivalence Study in Asthma

Study Overview
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Brief Summary
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The purpose of this study is to determine whether MGR001 is equivalent to Advair Diskus when administered by inhalation in adult asthma patients

Official Title
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A Randomized, Double-blind, Double Dummy, Parallel Group Study to Determine the Local Equivalence of Multiple Doses of MGR001 to Advair Diskus Administered Via Oral Inhalation in Adult Asthma Patients

Conditions
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Asthma

Intervention / Treatment
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* Drug: MGR001 (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate)
* Drug: Advair (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key inclusion criteria include: Male or female subjects aged ≥18 years. Females may be of either childbearing or non-childbearing potential Physician diagnosed history of asthma for at least 12 weeks prior to screening pre-bronchodilator FEV1 60-85% at screening and other specified visits Post-bronchodilator reversibility >/=12% Non-smokers and prior smokers with no history of smoking within the past 12 months prior to screening and a total smoking history of ≤10 pack-years Subjects able to discontinue asthma medications for the duration of the study and be maintained using albuterol as required Body mass index between 18-40 kg/m2 inclusive Key exclusion criteria include: Presence or recent history of any other active, severe, progressive, and/or uncontrolled clinical disease, eg, poorly controlled Type 1 or 2 diabetes, seizure disorder or epilepsy, cerebrovascular accident, significant cardiac conduction abnormalities Respiratory conditions other than asthma and allergic rhinitis, including but not limited to: severe nasal polyposis or chronic rhinosinusitis, chronic obstructive pulmonary disease, bronchiectasis, Churg-Strauss Disease, lung resection, pulmonary fibrosis (primary or secondary), pulmonary hypertension, cystic fibrosis, sarcoidosis History of life-threatening asthma, defined as a history of asthma episode(s) requiring intubation, and/or associated with hypercapnia; respiratory arrest or hypoxic seizures, asthma related syncopal episode(s) In patient hospitalization (not including ER visits) for an asthma exacerbation within the past year or during the run in period An asthma exacerbation requiring change in asthma therapy or oral/IV corticosteroids in the 3 months prior to screening History of seasonally unstable asthma where the season will coincide with the subject's participation in the study Use of prescription or non-prescription drugs, including beta blockers, tricyclic antidepressants, oral decongestants, benzodiazepines, digitalis, phenothiazines, monoamine oxidase inhibitors, etc Suspected hypersensitivity to the study drugs (including lactose) or severe milk protein allergy Clinically significant abnormalities in the screening ECG Evidence of alcohol or drug abuse or dependency within 6 months prior to screening

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MGR001<br>MGR001 administered two times per day by inhalation throughout the study | Drug: MGR001 (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate)<br>* Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the CRC749 inhaler device<br>|
| Active Comparator: Advair Diskus<br>Advair Diskus administered two times per day by inhalation throughout the study | Drug: Advair (Fixed dose combination of Fluticasone propionate and salmeterol xinafoate)<br>* Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered via the Diskus inhaler device<br>|
| Placebo Comparator: Placebo<br>Placebo for Advair Diskus and MGR001 administered two times per day by inhalation throughout the study | Drug: Placebo<br>* Placebo administered via the CRC749 and Diskus devices<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Exhaled Volume in 1 Sec (FEV1) Area Under the Effect Curve on Day 1 (Assay Sensitivity) | The FEV1 AUEC(0-12) on Day 1 was calculated from FEV1 measurements collected 30 minutes prior to morning dose, 0 minutes prior to morning dose, and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours following completion of dosing on Day 1 (Visit 3). The baseline for the FEV1 AUEC(0-12) endpoint was the mean of the 2 predose FEV1 measures. To confirm assay sensitivity, both active treatments (MGR001 and Advair Diskus) had to be significantly superior to placebo | 0-12 hours after dosing on Day 1 | 
| Forced Exhaled Volume in 1 Sec (FEV1) Area Under the Effect Curve on Day 1 (Bioequivalence) | The FEV1 AUEC(0-12) on Day 1 was calculated from FEV1 measurements collected 30 minutes prior to morning dose, 0 minutes prior to morning dose, and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours following completion of dosing on Day 1 (Visit 3). The baseline for the FEV1 AUEC(0-12) endpoint was the mean of the 2 predose FEV1 measures | 0-12 hours after dosing on Day 1 | 
| FEV1 Trough Value (Assay Sensitivity) | Change from baseline in trough (pre-dose) FEV1 at Day 29 was based on 2 pre-dose FEV1 assessments performed 30 minutes apart on Day 29. Baseline was calculated by taking the mean of [prebronchodilator FEV1 measured at a run-in visit and the mean of 2 predose FEV1 measures taken at Day 1]. To confirm assay sensitivity, both active treatments (MGR001 and Advair Diskus) had to be significantly superior to placebo. | Day 1 and Day 29 | 
| FEV1 Trough Value (Bioequivalence) | Change from baseline in trough (pre-dose) FEV1 at Day 29 was based on 2 pre-dose FEV1 assessments performed 30 minutes apart on Day 29. Baseline was calculated by taking the mean of [prebronchodilator FEV1 measured at a run-in visit and the mean of 2 predose FEV1 measures taken at Day 1] | Day 1 and Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, fluticasone, salmeterol, CRC749, Diskus, Advair, FEV1, MGR001