Study to Evaluate the 24-Hour Pulmonary Function Profile of Fluticasone Furoate/Vilanterol (FF/VI) Inhalation Powder 100/25mcg Once Daily Compared With Tiotropium Bromide Inhalation Powder 18mcg Once Daily in Subjects With COPD Who Have or Are At Risk for Co-morbid Cardiovascular Disease

A 12-Week Study to Evaluate the 24-Hour Pulmonary Function Profile of Fluticasone Furoate /Vilanterol (FF/VI) Inhalation Powder 100/25mcg Once-Daily Via a Novel Dry Powder Inhaler Compared With Tiotropium Bromide Inhalation Powder 18mcg Delivered Once-Daily Via the HandiHaler in Subjects With Chronic Obstructive Pulmonary Disease (COPD) Who Have or Are at Risk for Co-morbid Cardiovascular Disease

The purpose of this study is to evaluate the 24-hour spirometry effect (FEV1) of Fluticasone Furoate/Vilanterol Inhalation Powder 100/25mcg once daily compared with tiotropium bromide inhalation powder 18mcg once daily over a 12-week treatment period in subjects with COPD who have or are at risk for co-morbid cardiovascular disease

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: fluticasone furoate/vilanterol 100/25mcg; Drug: tiotropium bromide 18mcg

Detailed Description

This is a randomized, double-blind, double-dummy, multi-center, parallel-group study. Subjects who meet the eligibility criteria at Screening and at the end of a 2-week Run-In Period will enter a 12-week Treatment Period. There will be a 7-day Follow-up Period after the Treatment Period.

• Study Type: Interventional
• Enrollment (Actual): 623
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • GSK Investigational Site
  • Nova Scotia
    • Truro, Nova Scotia, Canada, B2N 1L2
      • GSK Investigational Site
  • Ontario
    • Toronto, Ontario, Canada, M5V 2T3
      • GSK Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H4J 1C5
      • GSK Investigational Site
    • Montreal, Quebec, Canada, H2W 1T8
      • GSK Investigational Site
    • Montreal, Quebec, Canada, H4N 3C5
      • GSK Investigational Site
    • Sherbrooke, Quebec, Canada, J1H 1Z1
      • GSK Investigational Site
    • St-Charles-Borromée, Quebec, Canada, J6E 2B4
      • GSK Investigational Site
    • St-Romuald, Quebec, Canada, G6W 5M6
      • GSK Investigational Site
• Czechia
  • Kralupy nad Vltavou, Czechia, 278 01
    • GSK Investigational Site
  • Kromeriz, Czechia, 767 55
    • GSK Investigational Site
  • Teplice, Czechia, 415 10
    • GSK Investigational Site
  • Trebic, Czechia, 674 01
    • GSK Investigational Site
  • Zamberk, Czechia, 564 01
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 10117
    • GSK Investigational Site
  • Berlin, Germany, 10717
    • GSK Investigational Site
  • Berlin, Germany, 10787
    • GSK Investigational Site
  • Berlin, Germany, 10789
    • GSK Investigational Site
  • Brandenburg
    • Cottbus, Brandenburg, Germany, 03050
      • GSK Investigational Site
    • Ruedersdorf, Brandenburg, Germany, 15562
      • GSK Investigational Site
  • Hessen
    • Frankfurt, Hessen, Germany, 60596
      • GSK Investigational Site
    • Neu-Isenburg, Hessen, Germany, 63263
      • GSK Investigational Site
  • Mecklenburg-Vorpommern
    • Schwerin, Mecklenburg-Vorpommern, Germany, 19055
      • GSK Investigational Site
  • Sachsen
    • Dresden, Sachsen, Germany, 01069
      • GSK Investigational Site
    • Leipzg, Sachsen, Germany, 04109
      • GSK Investigational Site
  • Sachsen-Anhalt
    • Magdeburg, Sachsen-Anhalt, Germany, 39112
      • GSK Investigational Site
  • Schleswig-Holstein
    • Grosshansdorf, Schleswig-Holstein, Germany, 22927
      • GSK Investigational Site
• Poland
  • Bialystok, Poland
    • GSK Investigational Site
  • Czestochowa, Poland, 42-200
    • GSK Investigational Site
  • Dzialdowo, Poland, 13-200
    • GSK Investigational Site
  • Krakow, Poland, 31-024
    • GSK Investigational Site
  • Piekary Slaskie, Poland, 41-940
    • GSK Investigational Site
  • Slupsk, Poland, 76-200
    • GSK Investigational Site
  • Tarnow, Poland, 33-100
    • GSK Investigational Site
• Romania
  • Bucharest, Romania, 050159
    • GSK Investigational Site
  • Bucharest, Romania, 020125
    • GSK Investigational Site
  • Bucharest, Romania, 030317
    • GSK Investigational Site
  • Bucuresti, Romania, 70000
    • GSK Investigational Site
  • Cluj Napoca, Romania, 400371
    • GSK Investigational Site
  • Cluj-Napoca, Romania, 400371
    • GSK Investigational Site
  • Constanta, Romania, 900002
    • GSK Investigational Site
  • Iasi, Romania, 700115
    • GSK Investigational Site
  • Suceava, Romania, 720284
    • GSK Investigational Site
  • Timisoara, Romania, 300310
    • GSK Investigational Site
• United States
  • California
    • Newport Beach, California, United States, 92663
      • GSK Investigational Site
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • GSK Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • GSK Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • GSK Investigational Site
  • Oregon
    • Medford, Oregon, United States, 97404
      • GSK Investigational Site
  • South Carolina
    • Gaffney, South Carolina, United States, 29340
      • GSK Investigational Site
    • Greenville, South Carolina, United States, 29615
      • GSK Investigational Site
    • Seneca, South Carolina, United States, 29678
      • GSK Investigational Site
    • Spartanburg, South Carolina, United States, 29303
      • GSK Investigational Site
    • Union, South Carolina, United States, 29379
      • GSK Investigational Site
  • Virginia
    • Newport News, Virginia, United States, 23606
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed and dated written informed consent
• Male or females ≥ 40 years of age
• Females must be post-menopausal or using a highly effective method for avoidance of pregnancy
• Established clinical history of COPD by ATS/ERS definition
• Post-albuterol spirometry criteria: FEV1/FVC ratio ≤ 0.70 and FEV1 ≥30 to ≤ 70% of predicted normal (NHANES III)
• Former or current smoker ≥10 pack years
• A history of diagnosed cardiovascular disease or a prior cardiovascular event including any of the following:
• Established (i.e., by clinical signs or imaging studies) coronary artery disease (CAD)
• Established (i.e., by clinical signs or imaging studies) peripheral vascular (i.e., arterial) disease (PVD)
• Previous stroke
• Objectively confirmed transient ischemic attack (TIA) (i.e., transient neurological deficit documented by a health-care professional)
• Previous myocardial infarction (MI) (Note: An MI within 6 months prior to Visit 1 is exclusionary)

OR

• Presence of one of the following cardiovascular risk factors (in addition to being a former/current smoker):
• Current diagnosis of hypertension
• Current diagnosis of hypercholesterolemia
• Diabetes mellitus treated with pharmacotherapy

Exclusion Criteria:

• Current diagnosis of asthma
• Subjects with other respiratory disorders including α1-antitrypsin deficiency as the underlying cause of COPD, active tuberculosis, lung cancer, bronchiectasis (Note: focal bronchiectasis is not exclusionary), sarcoidosis, pulmonary fibrosis (Note: focal fibrotic pulmonary lesions are not exclusionary), pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases
• Lung volume reduction surgery within previous 12 months
• Clinically significant abnormalities not due to COPD by chest X-ray or CT scan
• Hospitalized for poorly controlled COPD within 12 weeks of Screening
• Poorly controlled COPD 6 weeks prior to Screening, defined as acute worsening of COPD that is managed by the subject with corticosteroids or antibiotics or that requires treatment prescribed by a physician
• Lower respiratory infection requiring antibiotics 6 weeks prior to Screening
• A moderate or severe COPD exacerbation and/or a lower respiratory tract infection (including pnuemonia) during the Run-In Period
• An abnormal, clinically significant finding in any liver chemistry, biochemical, or haematology tests at Screening (Visit 1) or upon repeat prior to randomization
• An abnormal, clinically significant ECG finding at Screening (Visit 1) or upon repeat prior to randomization
• An abnormal, clinically significant Holter finding at Screening (Visit 1) or upon repeat prior to randomization (sub-set of subjects)
• Historical or current evidence of clinically significant (in opinion of the Investigator) and unstable disease such as cardiovascular (e.g., patients requiring ICD, pacemaker requiring a ventricular pace rate set at >60 bpm, uncontrolled hypertension, New York Heart Association Class IV (New York Heart Association,1994), known left ventricular ejection fraction <30%), neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease), peptic ulcer disease, or haematological abnormalities
• Carcinoma not in complete remission for at least 5 years
• History of allergy or hypersensitivity to any of the study medications (e.g., anticholinergic/muscarinic receptor antagonist, beta2-agonist, corticosteroid) or components of the inhalation powder (e.g., lactose, magnesium stearate) or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the study physician contraindicates study participation or use of an inhaled anticholinergic. In addition, subjects with a history of severe milk protein allergy that, in the opinion of the Investigator, contraindicates the subject's participation will also be excluded
• Known/suspected history of alcohol or drug abuse in the last 2 years
• Women who are pregnant or lactating or plan to become pregnant
• Subjects medically unable to withhold albuterol /salbutamol for 4 hours prior to spirometry testing at each study visit
• Use of certain medications such as bronchodilators and corticosteroids for the protocol-specific times prior to Visit 1 (the Investigator will discuss the specific medications)
• Long Term Oxygen Therapy (LTOT) or nocturnal oxygen therapy >12 hours a day
• Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Screening or during the study
• Failure to demonstrate adequate compliance defined as completion of the Diary Card (completed all diary entries on at least 4 of the last 7 consecutive days), the ability to withhold COPD medications and to keep clinic visit appointments
• Non-compliance or inability to comply with study procedures or scheduled visits
• History of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study
• Affiliation with investigator site
• Women who are pregnant or lactating or are planning on becoming pregnant during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: fluticasone furoate/vilanterol; inhaled corticosteroid (ICS)/long-acting beta2-agonist (LABA)	Drug: fluticasone furoate/vilanterol 100/25mcg; inhalation powder
Active Comparator: tiotropium bromide; anticholinergic	Drug: tiotropium bromide 18mcg; inhalation powder; Other Names: Spiriva

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline Trough in 24-hour Weighted Mean FEV1 on Treatment Day 84	Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. The weighted mean was calculated from the pre-dose FEV1 and post-dose FEV1 measurements at 5, 15, 30 minutes and 1, 2, 4, 6, 8, 12, 13, 14, 16, 20, and 24 hours on Treatment Day 84. Baseline trough FEV1 was the mean of the two assessments made 30 and 5 minutes pre-dose on Treatment Day 1. Change from Baseline (BL) was calculated as the average of the Day 84 values minus the Baseline value. Analysis was performed using an analysis of covariance (ANCOVA) model with covariates of BL FEV1, exacerbation history and reversibility stratum, smoking status at screening, country, and treatment group.	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. Time of onset was calculated over 0 to 4 hours (5 minutes (min), 15 min, 30 min, 60 min, 120 min, and 240 min) post-dose. Time to onset was analyzed using a log-rank test, stratified by exacerbation history and reversibility stratum.	Baseline and Day 1
Change From Baseline in Trough FEV1 at Treatment Day 84	Pulmonary function was measured by FEV1. Trough FEV1 was defined as the 24-hour FEV1 assessment, which was obtained on Day 84. Baseline is defined 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 84 values minus the Baseline value. Analysis was performed using an ANCOVA model with covariates of BL FEV1, exacerbation history and reversibility stratum, smoking status at screening, country, and treatment group.	Baseline and Day 84

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 21, 2012

Study Registration Dates

• First Submitted: June 21, 2012
• First Submitted That Met QC Criteria: June 21, 2012
• First Posted (Estimate): June 25, 2012

Study Record Updates

• Last Update Posted (Actual): November 9, 2017
• Last Update Submitted That Met QC Criteria: October 9, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Cardiovascular disease; Cardiovascular event
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases, Obstructive; Cardiovascular Diseases; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Respiratory Aspiration; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anti-Inflammatory Agents; Dermatologic Agents; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Fluticasone; Xhance; Tiotropium Bromide; Bromides
• Other Study ID Numbers: 115805

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Informed Consent Form
   Information identifier: 115805
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Study Protocol
   Information identifier: 115805
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: 115805
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Dataset Specification
   Information identifier: 115805
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 115805
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Individual Participant Data Set
   Information identifier: 115805
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Statistical Analysis Plan
   Information identifier: 115805
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register