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

Conditions: Pulmonary Disease, Chronic Obstructive

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

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.

Eligibility criteria:
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

Keywords: cardiovascular event cardiovascular disease