A Phase III, 4-week, Randomized, Double-blind Study to Compare 'Closed' Triple Therapy (FF/UMEC/VI), 'Open' Triple Therapy (FF/VI + UMEC) and Dual Therapy (FF/VI) in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Overview
- Phase
- Phase 3
- Intervention
- Fluticasone furoate 100 mcg + Umeclidinium 62.5 mcg+Vilanterol 25 mcg
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Sponsor
- GlaxoSmithKline
- Locations
- 1
- Primary Endpoint
- Change from baseline in trough forced expiratory volume in one second (FEV1) on Day 29
- Status
- Withdrawn
- Last Updated
- 9 years ago
Overview
Brief Summary
The primary purpose of this study is to assess the equivalence of closed triple therapy Fluticasone Furoate (FF)/Umeclidinium (UMEC)/Vilanterol (VI) to open triple therapy (FF/VI + UMEC), with a comparison of both triple therapies to dual therapy (FF/VI) on lung function.
This is a phase III, 4-week, randomized, double-blind, parallel group, multicenter study comparing FF/UMEC/VI (100 micrograms [mcg]/62.5 mcg/25 mcg) delivered via a single ELLIPTA® inhaler ('closed' triple) + matching placebo ELLIPTA inhaler, FF/VI + UMEC delivered via two ELLIPTA inhalers ('open' triple) and FF/VI via a single ELLIPTA inhaler + matching placebo ELLIPTA inhaler, all once daily. The total duration of subject participation will be approximately 7 weeks, consisting of a 2-week run-in period, 4-week treatment period and a 1-week follow-up period.
ELLIPTA is a registered trade mark of the GSK group of companies.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A signed and dated written informed consent prior to study participation.
- •Outpatient
- •Subjects 40 years of age or older at Screening (V1).
- •Male or female subjects.
- •A female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin \[hCG\] test), not lactating, and at least one of the following conditions applies:
- •Non-reproductive potential as defined in the protocol
- •Reproductive potential and agrees to follow methods specified in the protocol for avoiding pregnancy in Females of Reproductive Potential (FRP), from 30 days prior to the first dose of study treatment and until after the last dose of study treatment and completion of the follow-up visit.
- •An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society
- •Current or former cigarette smokers with a history of cigarette smoking of \>=10 pack-years at Screening \[number of pack years = (number of cigarettes per day / 20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)\]. Previous smokers are defined as those who have stopped smoking for at least 6 months prior to Screening (V1).
- •A score of \>=10 on the COPD Assessment Test (CAT) at Screening (V1).
Exclusion Criteria
- •Women who are pregnant or lactating or are planning on becoming pregnant during the study.
- •Subjects with a current diagnosis of asthma. (Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD, which is the primary cause of their respiratory symptoms).
- •Subjects with alpha-1-antitrypsin deficiency as the underlying cause of COPD.
- •Subjects with active tuberculosis are excluded. Subjects with other respiratory disorders (e.g. clinically significant: bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases) are excluded if these conditions are the primary cause of their respiratory symptoms.
- •Subjects with lung volume reduction surgery (including procedures such as endobronchial valves) within the 12 months prior to Screening (V1).
- •Immune suppression (e.g. advanced Human Immunodeficiency Virus (HIV) with high viral load and low CD4 count, Lupus on immunosuppressants that would increase risk of pneumonia) or other risk factors for pneumonia (e.g. neurological disorders affecting control of the upper airway, such as Parkinson's Disease, Myasthenia Gravis).subjects at potentially high risk for pneumonia (e.g. very low BMI, severely malnourished, or very low FEV1) will only be included at the discretion of the investigator.
- •Pneumonia and/or moderate or severe COPD exacerbation that has not resolved at least 14 days prior to Screening (V1) and at least 30 days following the last dose of oral/systemic corticosteroids (if applicable).
- •Other respiratory tract infections that have not resolved at least 7 days prior to Screening (V1).
- •Chest x-ray reveals evidence of pneumonia or a clinically significant abnormality not believed to be due to the presence of COPD, or another condition that would hinder the ability to detect an infiltrate on chest x-ray (e.g. significant cardiomegaly, pleural effusion or scarring). All subjects will have a chest x-ray at Screening (V1) \[or historical radiograph or CT scan obtained within 12 months prior to Screening. Subjects who have experienced pneumonia and/or moderate or severe COPD exacerbation within 12 months of Screening (V1) must provide a post pneumonia/exacerbation chest x-ray or have a chest x-ray conducted at Screening (V1)\].
- •For sites in Germany: If a chest x-ray (or CT scan) within 12 months prior to Screening (V1) is not available, approval to conduct a diagnostic chest x-ray will need to be obtained from the Federal Office for Radiation Protection (BfS).
Arms & Interventions
FF/UMEC/VI (100/62.5/25 mcg) + placebo
Subjects will receive FF/UMEC/VI 100 mcg/62.5 mcg/25 mcg delivered via single ELLIPTA inhaler ('closed' triple) and matching placebo via ELLIPTA inhaler once daily in the morning for 4 weeks as per the randomization. Albuterol/salbutamol will be used as rescue medication throughout the study as needed.
Intervention: Fluticasone furoate 100 mcg + Umeclidinium 62.5 mcg+Vilanterol 25 mcg
FF/UMEC/VI (100/62.5/25 mcg) + placebo
Subjects will receive FF/UMEC/VI 100 mcg/62.5 mcg/25 mcg delivered via single ELLIPTA inhaler ('closed' triple) and matching placebo via ELLIPTA inhaler once daily in the morning for 4 weeks as per the randomization. Albuterol/salbutamol will be used as rescue medication throughout the study as needed.
Intervention: Fluticasone furoate 100 mcg + Vilanterol 25 mcg
FF/UMEC/VI (100/62.5/25 mcg) + placebo
Subjects will receive FF/UMEC/VI 100 mcg/62.5 mcg/25 mcg delivered via single ELLIPTA inhaler ('closed' triple) and matching placebo via ELLIPTA inhaler once daily in the morning for 4 weeks as per the randomization. Albuterol/salbutamol will be used as rescue medication throughout the study as needed.
Intervention: Umeclidinium 62.5 mcg
FF/UMEC/VI (100/62.5/25 mcg) + placebo
Subjects will receive FF/UMEC/VI 100 mcg/62.5 mcg/25 mcg delivered via single ELLIPTA inhaler ('closed' triple) and matching placebo via ELLIPTA inhaler once daily in the morning for 4 weeks as per the randomization. Albuterol/salbutamol will be used as rescue medication throughout the study as needed.
Intervention: Placebo ELLIPTA inhaler
FF/UMEC/VI (100/62.5/25 mcg) + placebo
Subjects will receive FF/UMEC/VI 100 mcg/62.5 mcg/25 mcg delivered via single ELLIPTA inhaler ('closed' triple) and matching placebo via ELLIPTA inhaler once daily in the morning for 4 weeks as per the randomization. Albuterol/salbutamol will be used as rescue medication throughout the study as needed.
Intervention: Albuterol/Salbutamol
FF/VI 100 mcg/25 mcg + UMEC 62.5 mcg
Subjects will receive FF/VI (100 mcg/25 mcg) and UMEC 62.5 mcg delivered via two ELLIPTA inhaler ('open' triple) once daily in the morning for 4 weeks as per the randomization. Albuterol/salbutamol will be used as rescue medication throughout the study as needed.
Intervention: Fluticasone furoate 100 mcg + Umeclidinium 62.5 mcg+Vilanterol 25 mcg
FF/VI 100 mcg/25 mcg + UMEC 62.5 mcg
Subjects will receive FF/VI (100 mcg/25 mcg) and UMEC 62.5 mcg delivered via two ELLIPTA inhaler ('open' triple) once daily in the morning for 4 weeks as per the randomization. Albuterol/salbutamol will be used as rescue medication throughout the study as needed.
Intervention: Fluticasone furoate 100 mcg + Vilanterol 25 mcg
FF/VI 100 mcg/25 mcg + UMEC 62.5 mcg
Subjects will receive FF/VI (100 mcg/25 mcg) and UMEC 62.5 mcg delivered via two ELLIPTA inhaler ('open' triple) once daily in the morning for 4 weeks as per the randomization. Albuterol/salbutamol will be used as rescue medication throughout the study as needed.
Intervention: Umeclidinium 62.5 mcg
FF/VI 100 mcg/25 mcg + UMEC 62.5 mcg
Subjects will receive FF/VI (100 mcg/25 mcg) and UMEC 62.5 mcg delivered via two ELLIPTA inhaler ('open' triple) once daily in the morning for 4 weeks as per the randomization. Albuterol/salbutamol will be used as rescue medication throughout the study as needed.
Intervention: Albuterol/Salbutamol
FF/VI 100 mcg/25 mcg + placebo
Subjects will receive FF/ VI (100 mcg/25 mcg) delivered via single ELLIPTA inhaler and matching placebo via ELLIPTA inhaler once daily in the morning for 4 weeks as per the randomization. Albuterol/salbutamol will be used as rescue medication throughout the study as needed.
Intervention: Fluticasone furoate 100 mcg + Vilanterol 25 mcg
FF/VI 100 mcg/25 mcg + placebo
Subjects will receive FF/ VI (100 mcg/25 mcg) delivered via single ELLIPTA inhaler and matching placebo via ELLIPTA inhaler once daily in the morning for 4 weeks as per the randomization. Albuterol/salbutamol will be used as rescue medication throughout the study as needed.
Intervention: Placebo ELLIPTA inhaler
FF/VI 100 mcg/25 mcg + placebo
Subjects will receive FF/ VI (100 mcg/25 mcg) delivered via single ELLIPTA inhaler and matching placebo via ELLIPTA inhaler once daily in the morning for 4 weeks as per the randomization. Albuterol/salbutamol will be used as rescue medication throughout the study as needed.
Intervention: Albuterol/Salbutamol
Outcomes
Primary Outcomes
Change from baseline in trough forced expiratory volume in one second (FEV1) on Day 29
Time Frame: Up to Day 29
Forced Expiratory Volume (FEV1) is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second
Secondary Outcomes
- Change from baseline in trough FEV1 on Days 2, 28 and 29(Up to Day 29)
- Change from baseline in weighted mean (WM) FEV1 0-6 hours on Day 1 and Day 28 (in a subset)(Up to Day 28)
- Change from baseline in trough FEV1 on Day 2 and Day 28(Up to Day 28)
- Serial FEV1 over 0-6 hours on Day 1 and Day 28 (in a subset)(Up to Day 28)