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

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01627327
• Other study ID #: 115805
• Status: Completed
• Phase: Phase 3
• First received: June 21, 2012
• Last updated: October 9, 2017
• Start date: April 1, 2012
• Est. completion date: December 21, 2012

Study information

• Verified date: October 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 623
• Est. completion date: December 21, 2012
• Est. primary completion date: December 1, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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 a1-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

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Chronic Disease
• Lung Diseases
• Pulmonary Disease, Chronic Obstructive
• Respiratory Aspiration

Intervention

Drug:
• fluticasone furoate/vilanterol 100/25mcg
inhalation powder
• tiotropium bromide 18mcg
inhalation powder

Locations

Country	Name	City	State
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Sherbrooke	Quebec
Canada	GSK Investigational Site	St-Charles-Borromée	Quebec
Canada	GSK Investigational Site	St-Romuald	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Truro	Nova Scotia
Canada	GSK Investigational Site	Winnipeg	Manitoba
Czechia	GSK Investigational Site	Kralupy nad Vltavou
Czechia	GSK Investigational Site	Kromeriz
Czechia	GSK Investigational Site	Teplice
Czechia	GSK Investigational Site	Trebic
Czechia	GSK Investigational Site	Zamberk
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Cottbus	Brandenburg
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Grosshansdorf	Schleswig-Holstein
Germany	GSK Investigational Site	Leipzg	Sachsen
Germany	GSK Investigational Site	Magdeburg	Sachsen-Anhalt
Germany	GSK Investigational Site	Neu-Isenburg	Hessen
Germany	GSK Investigational Site	Ruedersdorf	Brandenburg
Germany	GSK Investigational Site	Schwerin	Mecklenburg-Vorpommern
Poland	GSK Investigational Site	Bialystok
Poland	GSK Investigational Site	Czestochowa
Poland	GSK Investigational Site	Dzialdowo
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Piekary Slaskie
Poland	GSK Investigational Site	Slupsk
Poland	GSK Investigational Site	Tarnow
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Cluj Napoca
Romania	GSK Investigational Site	Cluj-Napoca
Romania	GSK Investigational Site	Constanta
Romania	GSK Investigational Site	Iasi
Romania	GSK Investigational Site	Suceava
Romania	GSK Investigational Site	Timisoara
United States	GSK Investigational Site	Charlotte	North Carolina
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Coeur d'Alene	Idaho
United States	GSK Investigational Site	Gaffney	South Carolina
United States	GSK Investigational Site	Greenville	South Carolina
United States	GSK Investigational Site	Medford	Oregon
United States	GSK Investigational Site	Newport Beach	California
United States	GSK Investigational Site	Newport News	Virginia
United States	GSK Investigational Site	Seneca	South Carolina
United States	GSK Investigational Site	Spartanburg	South Carolina
United States	GSK Investigational Site	Union	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Germany,  Poland,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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

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