A Study to Assess the Efficacy of Fluticasone Furoate/Vilanterol (FF/VI) Inhalation Powder 100/25 mcg Once Daily Compared With Fluticasone Propionate/Salmeterol Inhalation Powder 250/50 mcg Twice Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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This will be a Phase IIIb multicentre, randomized, double-blind, double-dummy, 12-week parallel group study evaluating the effects of once daily in the morning treatment of FF/VI Inhalation Powder versus Fluticasone Propionate/Salmeterol Inhalation Powder twice daily on lung function in COPD subjects. Subjects will be screened and will enter a 2-week, single-blind (placebo), Run-In Period to evaluate the subject's adherence with study treatment, study procedures and assessment of disease stability. At the end of the Run-In Period, subjects will return to the Clinic and who meet all of the Randomization Criteria will be randomized to double-blind study medication (12-week treatment period). Subjects will be randomized to receive either FF/VI 100/25 via NDPI or Fluticasone Propionate/Salmeterol 250/50mcg via ACCUHALER/DISKUS. Matching placebos will be available in NDPI and ACCUHALER/DISKUS. Each morning (approximately 6-10 AM) subjects will take 1 inhalation from the NDPI followed by 1 inhalation from the ACCUHALER/DISKUS. Each evening (approximately 6-10 PM), approximately 12 hours after the morning dose with blinded study medication, subjects will take 1 inhalation from the ACCUHALER/DISKUS. Subjects will return to the clinic at the end of the treatment period. A follow-up phone contact will be performed approximately 7 days after the last clinic visit. The overall study duration (Screening to Follow-up) for each subject is approximately 15 weeks.

Official Title
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A 12-Week Study to Evaluate the 24-Hour Pulmonary Function Profile of Fluticasone Furoate/Vilanterol (FF/VI) Inhalation Powder 100/25 mcg Once Daily Compared With Fluticasone Propionate/Salmeterol Inhalation Powder 250/50 mcg Twice Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: FF/VI 100/25 Inhalation Powder NDPI
* Drug: Fluticasone Propionate/Salmeterol 250/50 Inhalation Powder ACCUHALER/DISKUS
* Drug: Placebo Inhalation Powder NDPI
* Drug: Placebo Inhalation Powder ACCUHALER/DISKUS
* Drug: Salbutamol as needed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A male or female >=40 years of age at Screening (Visit 1). Capable of giving written informed consent. Female subjects must be post-menopausal or using a highly effective method for avoidance of pregnancy. Subjects with a clinical history of COPD in accordance with the following definition by the American Thoracic Society/European Respiratory Society. Subject with a measured post-albuterol (salbutamol) FEV1/forced vital capacity(FVC) ratio of <=0.70 at Screening. Subjects with a measured post-albuterol (salbutamol) FEV1 <=70% of predicted normal values. Subjects with a current or prior history of ≥10 pack-years of cigarette smoking at Screening. Exclusion Criteria: Current diagnosis of asthma. (Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD). Other respiratory disorders (alpha1-antitrypsin deficiency as the underlying cause of COPD, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, pulmonary fibrosis, pulmonary hypertension, interstitial lung diseases, or other active pulmonary diseases). Lung volume reduction surgery within the 12 months prior to Screening. Hospitalized due to poorly controlled COPD within 12 weeks of Screening. Poorly controlled COPD (occurrence of the following in the 6 weeks prior to Screening -Acute worsening of COPD that is managed by the subject with corticosteroids or antibiotics or that requires treatment prescribed by a physician). Lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to Screening. Moderate/severe COPD exacerbation/lower respiratory tract infection during Run-In Period. Abnormal and clinically significant 12-lead ECG at Screening Historical or current evidence of uncontrolled or clinically significant disease like cardiovascular, hypertension, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease), peptic ulcer disease, or haematological abnormalities. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study. History of hypersensitivity to any of the study medications or components of the inhalation powder; or history of severe milk protein allergy. Known or suspected history of alcohol or drug abuse within the last 2 years. Subjects who are medically unable to withhold their albuterol (salbutamol) and/or their ipratropium for the 4-hour period required prior to spirometry testing at each study visit. The subject has taken any other investigational drug within 30 days or 5 half-lives of the investigational product (IP) prior to the first dosing day in the current study. Use of additional medications prior to Screening (list of medications and time intervals are different for different class of medications and are indicated in the protocol) Subjects receiving treatment with long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen prn use (i.e., <=12 hours per day) is not exclusionary. Subjects who have participated in the acute phase of a Pulmonary Rehabilitation Program within 4 weeks prior to Screening Subjects at risk of non-compliance, or unable to comply with study procedures. Study investigators, sub-investigators, study coordinators, employees of a participating investigator or immediate family members of the aforementioned are excluded from participating in this study. Women who are pregnant or lactating or are planning on becoming pregnant during the study. Previously randomized to either the HZC113109 or HZC112352 clinical studies.

Ages Eligible for Study
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Minimum Age: 40 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FF/VI Inhalation Powder NDPI<br>Subjects randomized to the FF/VI 100/25 arm will take an active inhalation of study medication during their morning dosing from their NDPI and will have an inhalation of dummy medication (placebo) as their morning ACCUHALER/DISKUS dose and as their evening dose. | Drug: FF/VI 100/25 Inhalation Powder NDPI<br>* Subjects randomized to the FF/VI Inhalation Powder Novel Dry Powder Inhaler (NDPI) arm will receive a single inhalation of 100 mcg FF and 25 mcg VI via NDPI every morning for 12 weeks.<br>Drug: Placebo Inhalation Powder ACCUHALER/DISKUS<br>* Subjects randomized to the FF/VI Inhalation Powder NDPI arm will receive a single inhalation of placebo inhalation powder via ACCUHALER/DISKUS once in the morning and once in the evening for 12 weeks.<br>Drug: Salbutamol as needed<br>* Salbutamol inhalation powder<br>|
| Active Comparator: Fluticasone Propionate/Salmeterol Inhalation Powder<br>Subjects randomized to the Fluticasone Propionate/Salmeterol Inhalation Powder 250/50mcg arm will have an active dose of medication during both their morning and evening treatments from the ACCUHALER/DISKUS and a dummy placebo dose in the morning from their NDPI. | Drug: Fluticasone Propionate/Salmeterol 250/50 Inhalation Powder ACCUHALER/DISKUS<br>* Subjects randomized to the Fluticasone Propionate/Salmeterol Inhalation Powder ACCUHALER/DISKUS arm will receive a single inhalation of 250 mcg Fluticasone Propionate and 50 mcg Salmeterol via ACCUHALER/DISKUS once in the morning and once in the evening for 12 weeks.<br>* Other names: ACCUHALER and DISKUS are registered trade marks of the GlaxoSmithKline Group of companies;Drug: Placebo Inhalation Powder NDPI<br>* Subjects randomized to the Fluticasone Propionate/Salmeterol Inhalation Powder ACCUHALER/DISKUS arm will receive a single inhalation of placebo inhalation powder via NDPI every morning for 12 weeks.<br>* Other names: ACCUHALER and DISKUS are registered trade marks of the GlaxoSmithKline Group of companies;Drug: Salbutamol as needed<br>* Salbutamol inhalation powder<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Trough in Weighted-mean 24-hour Serial Forced Expiratory Volume in One Second (FEV1) on Treatment Day 84 | FEV1 is a measure of lung function and is defined as the volume of air that can be forcefully exhaled in one second. The weighted mean was calculated from the pre-dose FEV1 and the post-dose FEV1 measurements taken at 5, 15, 30, and 60 minutes and 2, 4, 6, 8, 12, 13, 14, 16, 20, and 24 hours on Treatment Day 84. Baseline trough FEV1 was calculated as the mean of the two assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1. The weighted mean was derived by calculating the area under curve, and then dividing by the relevant time interval. The weighted mean change from Baseline was calculated as the weighted mean of the 24-hour serial FEV1 measurements on Day 84 minus the Baseline trough FEV1 value. The analysis used an analysis of covariance (ANCOVA) model with covariates of Baseline FEV1, reversibility stratum, smoking status (at Screening), country, and treatment. | Baseline and Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Onset on Treatment Day 1 | Time to onset on Treatment Day 1 is defined as the time to an increase of 100 milliliters (mL) from Baseline in FEV1 during the 0- to 4-hour serial measurements (5, 15, 30, 60, 120, and 240 minutes post-dose). Participants who never met or exceeded a 100 mL increase over the Baseline value during the 4-hour serial measurements were censored at the actual time of their last FEV1 measurement. | Baseline and Day 1 | 
| Change From Baseline in Trough FEV1 on Treatment Day 85 | FEV1 is a measure of lung function and is defined as the volume of air that can be forcefully exhaled in one second. Trough FEV1 is defined as the 24-hour FEV1 assessment, which was obtained on Day 85. Baseline trough was calculated as the mean of the two assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1. Change from Baseline was calculated as the average of the Day 85 values minus the Baseline value. The analysis used an analysis of covariance (ANCOVA) model with covariates of Baseline FEV1, reversibility stratum, smoking status (at Screening), country, and treatment. | Baseline and Day 85 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vilanterol (VI), Novel Dry Powder Inhaler (NDPI), FEV1, Fluticasone Furoate (FF), COPD