Please select the eligibility criteria that correspond to the clinical trial below.
Title: A 12-week Study to Evaluate the 24-hour Pulmonary Function Profile of Fluticasone Furoate/Vilanterol (FF/VI) Inhalation Powder 100/25 mcg Once Daily Compared With Fluticasone Propionate/Salmeterol Inhalation Powder 250/50 mcg Twice Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Brief Summary: The purpose of this study is to evaluate the 24-hour spirometry effect (FEV1) of FF/VI 100/25mcg once daily compared with Fluticasone Propionate/Salmeterol 250/50mcg twice daily over a 12-week treatment period in subjects with COPD.


Options:
A: Inclusion criteria:

* Established clinical history of moderate to severe COPD.
* Post bronchodilator FEV1 of \< 50% of predicted normal.
* FEV1 / FVC ratio \<70%.
* Reversibility to 400mcg albuterol of less or equal to 10 predicted at Visit 1.
* Free from exacerbation in the 6 weeks prior to screening.
* Current or former smoker with a smoking history of = 10 pack-years and has a history of COPD exacerbations.

Exclusion criteria:

* Current asthma, eczema, atopic dermatitis and/or allergic rhinitis.
* Has a known respiratory disorder other than COPD (e.g. lung cancer, sarcoidosis, tuberculosis or lung fibrosis).
* Has narrow-angle glaucoma, prostatic hyperplasia or obstruction of the neck of the bladder that in the opinion of the investigator should prevent the subject from entering the study.
* Has undergone lung transplantation and/or lung volume reduction.
* Female who is a nursing mother.
* Requires regular (daily) long-term oxygen therapy (LTOT).
* Is receiving beta-blockers (except eye drops).
* Has a serious, uncontrolled disease likely to interfere with the study.
* Has received any other investigational drugs within the 4 weeks prior to Visit 1.
* Has, in the opinion of the investigator, evidence of alcohol, drug or solvent abuse.
* Has a known or suspected hypersensitivity to beta2-agonists, inhaled corticosteroids, anticholinergic agents or any components of the formulations (e.g. lactose or milk protein).
B: Inclusion Criteria:

* Patients with moderate to severe stable COPD (Stage II or Stage III) according to the current GOLD Guidelines (GOLD 2010).
* Patients with a post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) ≥ 30% and \< 80% of the predicted normal, and a post-bronchodilator FEV1/ Forced Vital Capacity (FVC) \< 0.70 at screening
* Current or ex-smokers who have a smoking history of at least 10 pack years (e.g. 10 pack years = 1 pack/day x 10 yrs, or ½ pack/day x 20 yrs).
* Symptomatic patients, according to daily electronic diary data between Visit 2 (Day -14) and Visit 3 (Day 1), with a total score of 1 or more on at least 4 of the last 7 days prior to Visit 3.

Exclusion Criteria:

* Pregnant or nursing (lactating) women
* Patients who, in the judgment of the investigator, or the responsible Novartis personnel, have a clinically relevant laboratory abnormality or a clinically significant condition before Visit 1.
* Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment or urinary retention. (BPH patients who are stable on treatment can be considered).
* Patients receiving medications in the classes listed in the protocol as prohibited.

Other protocol-defined inclusion/exclusion criteria apply and can be found in the study protocol
C: Inclusion Criteria:

* Signed and dated written informed consent
* Male or females ≥ 40 years of age
* Established clinical history of COPD by ATS/ERS definition
* Females are eligible to enter and participate if of non-childbearing potential, or if of child bearing potential, has a negative serum pregnancy test at screening, and agrees to one of the acceptable contraceptive methods listed in protocol, used consistently and correctly
* Former or current smoker \> 10 pack years
* Post-albuterol spirometry criteria: FEV1/FVC ratio ≤ 0.70 and FEV1 ≤ 70% of predicted normal (NHANES III)

Exclusion Criteria:

* Current diagnosis of asthma
* Subjects with other respiratory disorders including active tuberculosis, α1-antitrypsin deficiency, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, 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
* 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
* Uncontrolled or clinically significant (in opinion of PI) cardiovascular, hypertension, neurological, psychiatric, renal, hepatic, immunological, endocrine, peptic ulcer disease, or hematological abnormalities
* Carcinoma not in complete remission for at least 5 years
* Subjects with history of hypersensitivity to study medications (e.g., beta-agonists, corticosteroid) or components of inhalation powder (e.g., lactose, magnesium stearate)
* Subjects with history of severe milk protein allergy that, in opinion of study physician, contraindicates subject's participation
* 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 and/or ipratropium 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
* Non-compliance or inability to comply with study procedures or scheduled visits
* Affiliation with investigator site
D: Inclusion Criteria:

* Type of subject: Outpatient
* Informed consent: Subjects must give their signed and dated written informed consent to participate
* Gender: Male subjects or female subjects. 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 years of age at Screening (Visit 1)
* COPD diagnosis: Subjects with a clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society: COPD is a preventable and treatable disease characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it is also associated with significant systemic consequences.
* Severity of disease: Subjects with a measured post-albuterol (salbutamol) FEV1/ Forced Vital Capacity (FVC) ratio of \<=0.70 and FEV1 \>=30 to \<=70 percent of predicted normal values using Global Lung Function Initiative 2012 reference equations at Screening (Visit 1).
* Tobacco use: Subjects with a current or prior history of \>=10 pack-years of cigarette smoking at Screening (Visit 1). Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1.
* History of COPD exacerbation: A documented history (e.g., medical record verification) of at least one COPD exacerbation in the 12 months prior to Screening (Visit 1) that required either systemic/oral corticosteroids, antibiotics and/or hospitalization.
* Current symptoms of COPD: A Subject Diary combined symptom score (combination of breathlessness, cough, sputum, and night time awakenings requiring treatment with albuterol \[salbutamol\]) of \>=4 on at least 5 of the 7 days immediately preceding Visit 2 (Randomization)
* QTc Criteria: QTc \<450 msec or QTc \<480 msec for patients with bundle branch block.

Exclusion Criteria:

* Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
* Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD).
* Other respiratory disorders: Subjects with alpha1-antitrypsin deficiency as the underlying cause of COPD 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), primary pulmonary hypertension, interstitial lung diseases, or other active pulmonary diseases.
* Lung resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening (Visit 1).
* Chest X-ray (or computed tomography \[CT\] scan): Subjects with a chest X-ray (or CT scan) that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD. A chest X-ray must be taken at Screening (Visit 1) if a chest X-ray or CT scan is not available within 1 year prior to Screening (Visit 1).
* Hospitalization: Subjects who are hospitalized due to poorly controlled COPD that has not resolved at least 4 weeks prior to Screening (Visit 1) and at least 6 weeks following the last dose of systemic corticosteroids.
* Poorly controlled COPD: Subjects with poorly controlled COPD, defined as the occurrence of any of the following in the 6 weeks prior to Screening (Visit 1): Acute worsening of COPD that is managed by subject with systemic corticosteroids or antibiotics or that requires treatment prescribed by a physician.
* Lower respiratory tract infection: Subjects with lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to Screening (Visit 1).
* COPD exacerbation/lower respiratory tract infection during the Run-In Period: Subjects who experience a moderate/severe COPD exacerbation (As per definition of "COPD Exacerbations and Pneumonia" in protocol) and/or a lower respiratory tract infection (including pneumonia) during the Run-In Period.
* Abnormal, clinically significant laboratory finding: Subjects who have an abnormal clinical significant finding in any liver chemistry test at Screening (Visit 1) or upon repeat prior to randomization.
* Abnormal, clinically significant 12-lead ECG at Screening (Visit 1): Subjects who have an abnormal, clinically significant 12-Lead electrocardiogram (ECG) finding at Screening (Visit 1) or upon repeat prior to randomization.
* Other diseases/abnormalities: Subjects with historical or current evidence of clinically significant and unstable disease such as cardiovascular (e.g., patients requiring implantable cardioverter-defibrillators (ICD), pacemaker requiring a rate set \>60 beats per minute (bpm), uncontrolled hypertension, New Your Heart Association Class IV, known left ventricular ejection fraction \<30 percent) neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease), peptic ulcer disease, or hematological abnormalities.
* Liver disease: Subjects who have unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). Note: Subjects with chronic stable hepatitis B and C are eligible if the subject otherwise meets entry criteria (e.g., presence of hepatitis B surface antigen or positive hepatitis C test result within 3 months of screening). However, subjects with chronic stable hepatitis B are excluded if significant immunosuppressive or cytotoxic agents are administered, due to risk of hepatitis B reactivation, unless the hepatitis B antivirals are administered as outlined in the Chronic Hepatitis B American Association for the Study of Liver Diseases' (AASLD) Practice Guidelines.
* Cancer: Subjects with carcinoma that has not been in complete remission for at least 5 years. Carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin would not be excluded if the subject has been considered cured within 5 years since diagnosis.
* Contraindications: Subjects with a history of allergy or hypersensitivity to any of the study medications (e.g. beta-agonists, corticosteroids) or components of the inhalation powder (e.g., lactose, magnesium stearate). 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.
* Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years
* Medication prior to spirometry: Subjects who are medically unable to withhold their albuterol (salbutamol) or their ipratropium bromide for the 4-hour period required prior to spirometry testing at each study visit.
* Additional medication: 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)"
* Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen as needed (prn) use (i.e., \<=12 hours per day) is not exclusionary.
* Sleep apnea: Subjects with clinically significant sleep apnea who require use of continuous positive airway pressure (CPAP) device or non-invasive positive pressure ventilation (NIPPV).
* Pulmonary rehabilitation: Subjects who have participated in the acute phase of a Pulmonary Rehabilitation Program within 4 weeks prior to Screening (Visit 1) or who will enter the acute phase of a Pulmonary Rehabilitation Program during the study. Subjects who are in the maintenance phase of a Pulmonary Rehabilitation Program are not excluded.
* Non-Compliance during Run-In Period: Failure to demonstrate adequate compliance defined as completion of Diary Card (completed all diary entries on at least 5 of the last 7 consecutive days), the ability to withhold anti-COPD medications and to keep clinic visit appointments. In addition, subjects must have recorded the Run-In study medication use on at least 5 of the last 7, consecutive days of the Run-In period to continue in the study.
* Potential of non-compliance: Subjects at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.
* 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.
* Prior use of study medication/other investigational drugs: Subjects who have received an investigational drug within 30 days of entry into this study (Screening), or within 5 drug half-lives of the investigational drug, whichever is longer. Note: Subjects who participated in a previously completed study and/or were excluded/ withdrawn from an ongoing study that included/includes FF/VI and/or VI are eligible to participate in the current study, if they have not received investigational study medication within 30 days of Screening (Visit 1).
* 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.

Answer: C