Clinical trial NCT01627327: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: Cardiovascular event
Cardiovascular disease
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-06-25
Enrollment: 623
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

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.

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

Primary outcomes:
measure: Change From Baseline Trough in 24-hour Weighted Mean FEV1 on Treatment Day 84
timeFrame: Baseline and Day 84
Secondary outcomes:
measure: Time to Onset on Treatment Day 1
timeFrame: Baseline and Day 1
measure: Change From Baseline in Trough FEV1 at Treatment Day 84
timeFrame: Baseline and Day 84
Other outcomes:
Locations:
city: Newport Beach
country: United States
facility: GSK Investigational Site
state: California
city: Coeur d'Alene
country: United States
facility: GSK Investigational Site
state: Idaho
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Medford
country: United States
facility: GSK Investigational Site
state: Oregon
city: Gaffney
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Seneca
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Union
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Newport News
country: United States
facility: GSK Investigational Site
state: Virginia
city: Winnipeg
country: Canada
facility: GSK Investigational Site
state: Manitoba
city: Truro
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
city: St-Charles-Borromée
country: Canada
facility: GSK Investigational Site
state: Quebec
city: St-Romuald
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Kralupy nad Vltavou
country: Czechia
facility: GSK Investigational Site
city: Kromeriz
country: Czechia
facility: GSK Investigational Site
city: Teplice
country: Czechia
facility: GSK Investigational Site
city: Trebic
country: Czechia
facility: GSK Investigational Site
city: Zamberk
country: Czechia
facility: GSK Investigational Site
city: Cottbus
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Ruedersdorf
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Neu-Isenburg
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Schwerin
country: Germany
facility: GSK Investigational Site
state: Mecklenburg-Vorpommern
city: Magdeburg
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Leipzg
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Grosshansdorf
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Bialystok
country: Poland
facility: GSK Investigational Site
city: Czestochowa
country: Poland
facility: GSK Investigational Site
city: Dzialdowo
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Piekary Slaskie
country: Poland
facility: GSK Investigational Site
city: Slupsk
country: Poland
facility: GSK Investigational Site
city: Tarnow
country: Poland
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucharest
country: Romania
facility: GSK Investigational Site
city: Bucuresti
country: Romania
facility: GSK Investigational Site
city: Cluj Napoca
country: Romania
facility: GSK Investigational Site
city: Cluj-Napoca
country: Romania
facility: GSK Investigational Site
city: Constanta
country: Romania
facility: GSK Investigational Site
city: Iasi
country: Romania
facility: GSK Investigational Site
city: Suceava
country: Romania
facility: GSK Investigational Site
city: Timisoara
country: Romania
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: