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

GlaxoSmithKline (GSK)

Status and phase

Completed

Phase 3

Conditions

Pulmonary Disease, Chronic Obstructive

Treatments

Drug: tiotropium bromide 18mcg

Drug: fluticasone furoate/vilanterol 100/25mcg

Study type

Interventional

Funder types

Industry

Identifiers

NCT01627327

115805

Details and patient eligibility

About

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

Full 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.

Enrollment

623 patients

Sex

All

Ages

40+ years old

Volunteers

No Healthy Volunteers

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)

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