Study to evaluate the effect of fluticasone furoate/vilanterol on survival in subjects with chronic obstructive pulmonary disease

Conditions: Subjects with moderate Chronic Obstructive Pulmonary Disease (COPD)
MedDRA version: 16.0Level: PTClassification code 10009033Term: Chronic obstructive pulmonary diseaseSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2010-021638-72-NL

Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 16000

Inclusion Criteria

1. Type of subject: outpatient.
2. Informed consent: Subjects must give their signed and dated written informed
consent to participate.
3. Gender: Male or female. Female subjects must be post-menopausal or using a highly
effective method for avoidance of pregnancy. The decision to include or exclude
women of childbearing potential may be made at the discretion of the investigator in
accordance with local practice in relation to adequate contraception.
4. Age: =40 and = 80 years of age at Screening (Visit 1).
5. Tobacco use: Subjects with a current or prior history of =10 pack-years of cigarette
smoking at screening (Visit 1). Previous smokers are defined as those who have
stopped smoking for at least 6 months prior to Visit 1.
6. Airflow Obstruction
• Subjects with a measured post-albuterol/salbutamol FEV1 =50 and =70% of
predicted normal values calculated using NHANES III reference equations
[Hankinson, 1999; Hankinson, 2010] at Screening (Visit 1).
Post-bronchodilator spirometry will be performed approximately 15 minutes
after the subject has self-administered 4 inhalations (i.e., total 400mcg) of
albuterol/salbutamol via an MDI with a valved-holding chamber. The
FEV1/FVC ratio and FEV1 percent predicted values will be calculated.
7. Dyspnea:
Subjects must score 2 or higher on the modified Medical Research Council Dyspnea
scale (Visit 1)
8. Cardiovascular disease:
For patients >= 40 years of age: any one 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 arterial
disease (PAD)
Previous stroke
Previous MI
Diabetes mellitus with target organ disease
OR
For patients >=60 years of age: any 2 of the following:
Being treated for hypercholesterolemia
Being treated for hypertension
Being treated for diabetes mellitus
Being treated for peripheral vascular disease
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8000
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8000

Exclusion Criteria

1. Pregnancy: Women who are pregnant or lactating.
2. Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of
asthma are eligible if they also have a current diagnosis of COPD).
3. a1-antitrypsin deficiency: Subjects with known a-1 antitrypsin deficiency as the
underlying cause of COPD.
4. Other respiratory disorders: Subjects with active tuberculosis, lung cancer,
bronchiectasis, sarcoidosis, pulmonary fibrosis, pulmonary hypertension, interstitial
lung diseases or other active pulmonary diseases.
5. Lung resection or transplantation: Subjects with lung volume reduction surgery
within the 12 months prior to Screening or having had a lung transplant.
6. A moderate/severe COPD exacerbation that has not resolved at least 14 days prior to Visit 1 and at least 30 days following the last dose of oral corticosteroids (if
applicable).
7. Current severe heart failure (New York Heart Association class IV). Subjects will also be excluded if they have a known ejection fraction of <30% or if they have an
implantable cardioverter defibrillator (ICD).
8. Other diseases/abnormalities: Any life-threatening condition with life expectancy
<3 years, other than vascular disease or COPD, that might prevent the subject from
completing the study.
9. End stage chronic renal disease: Subjects will be excluded if on renal replacement
therapy (hemodialysis or peritoneal).
10. Drug/food allergy: Subjects with a history of hypersensitivity to any of the study
medications (e.g. beta-agonists, corticosteroid) or components of the inhalation
powder (e.g. lactose, magnesium stearate). In addition, patients with a history of
severe milk protein allergy that, in the opinion of the study physician, contraindicates
the subject’s participation will also be excluded.
11. Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years.
12. Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy
(LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day.
Oxygen prn use (i.e. =12 hours per day) is not exclusionary.
13. Questionable validity of consent: Subjects with a history of psychiatric disease,
intellectual deficiency, poor motivation or other conditions that will limit the validity
of informed consent to participate in the study or the potential compliance to study
procedures.
14. Affiliation with investigator site: Study investigators, sub-investigators, study
coordinators, employees of a participating investigator or immediate family members
of the aforementioned are excluded from participating in this study.
15. Additional medication: Use of the following medications within the following time
intervals prior to Visit 1 or during the study (unless otherwise specified): view protocol page 23 for further information.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary end point(s): Primary Efficacy Endpoint<br>• Time to death from any cause;Timepoint(s) of evaluation of this end point: Every 3 months for the duration of the study;Main Objective: The primary objective of this study is to prospectively evaluate the effect of Fluticasone Furoate (FF)/Vilanterol (VI) inhalation powder 100/25mcg QD compared with placebo on survival in subjects with moderate COPD (=50 and =70 % predicted FEV1) and a history of, or at increased risk for developing, cardiovascular disease.;Secondary Objective: • To evaluate the effect of FF/VI compared with placebo on the rate of decline in<br>FEV1<br>• To evaluate the effect of FF/VI compared with placebo on a cardiovascular<br>composite endpoint comprised of on-treatment CV death, myocardial infarction<br>, stroke, unstable angina and TIA.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Rate of decline in FEV1<br>• Time to CV event;Timepoint(s) of evaluation of this end point: rate of decline in FEV1 - only while on treatment<br>time to CV event - on and off treatment as we are doing for mortality

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