The purpose of this study is to determine if fluticasone furoate/vilanterol improves
survival in patients with chronic obstructive pulmonary disease with a history of or
increased risk of heart disease.
The mechanism by which SFC appears to be associated with a greater reduction in mortality in
these less severe COPD subjects with concomitant cardiovascular comorbidities is speculative
at present, but could potentially in part be related to a lessening of the degree of
inflammation in the systemic circulation, potential plaque stabilization and/or amelioration
of arterial stiffness.
ICS/LABA combinations that are currently available require twice daily administration. A
once daily ICS/LABA combination has the potential to improve patient compliance and as a
result, overall disease management.
The purpose of this study is to prospectively evaluate the effect of the once daily ICS/LABA
combination Fluticasone Furoate (FF)/Vilanterol (VI) on survival in subjects with moderate
COPD (>=50 and =<70 % predicted FEV1 ) and a history of, or at increased risk for
cardiovascular disease.
Inclusion Criteria:
- Type of subject: outpatient.
- Informed consent: Subjects must give their signed and dated written informed consent
to participate.
- 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.
- Age: >=40 and <=80 years of age at Screening (Visit 1).
- 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.
- Airflow Obstruction:
Subjects with a measured post-albuterol/salbutamol forced expiratory volume in 1 second
(FEV1)/(forced vital capacity)FVC ratio of <=0. 70 at Screening (Visit 1).
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 a metered dose inhaler (MDI )with a valved-holding chamber. The FEV1/FVC ratio and
FEV1 percent predicted values will be calculated.
- Symptoms of COPD: Subjects must score 2 or higher on the modified Medical Research
Council Dyspnea scale (Visit 1)
- 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 vascular disease (PVD)
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
Exclusion Criteria:
- Pregnancy: Women who are pregnant or lactating.
- 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).
- alpha 1-antitrypsin deficiency: Subjects with known alpha-1 antitrypsin deficiency as
the underlying cause of COPD.
- Other respiratory disorders: Subjects with active tuberculosis, lung cancer,
bronchiectasis, sarcoidosis, pulmonary fibrosis, pulmonary hypertension, interstitial
lung diseases or other active pulmonary diseases.
- Lung resection or transplantation: Subjects with lung volume reduction surgery within
the 12 months prior to Screening or having had a lung transplant.
- 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).
- 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).
- 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.
- End stage chronic renal disease: Subjects will be excluded if on renal replacement
therapy (hemodialysis or peritoneal).
- 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.
- Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug
abuse within the last 2 years.
- 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.
- 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.
- 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.
- Additional medication: Use of the following medications within the following time
intervals prior to Visit 1 or during the study (unless otherwise specified):
Medication No use within the following time intervals prior to Screening or thereafter at
any time during the study (unless otherwise specified) Inhaled Long acting beta-agonists
(LABA) 48 hours
ICS/LABA combination products
48 hours Inhaled corticosteroids
48
hours Tiotropium
1 week Systemic, Oral,
parenteral, intra-articular corticosteroids
30 days (oral and systemic corticosteroids may be used to treat COPD exacerbations
during the study) Cytochrome P450 3A4 strong inhibitors including but not limited to
antiretrovirals (protease inhibitors) (e. g.Indinavir, Nelfinavir, Ritonavir, Saquinavir);
Imidazole and Triazole anti-fungals (e. g. Ketaconazole, Itraconazole); Clarithromycin,
Telithromycin, Amiodarone, and Nefazodone
6 weeks Grapefruit is allowed up to Visit 1,
then limited to no more than one glass of grapefruit juice (250 mL/ 8 ounces) or one
grapefruit per day Any other investigational drug
30 days or 5 half lives whichever is longer.
US GSK Clinical Call Center, Phone: 877-379-3718, Email: GSKClinicalSupportHD@gsk.com
