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.