Please select the eligibility criteria that correspond to the clinical trial below.
Title: A 24-Week Study to Evaluate the Efficacy and Safety of Fluticasone Furoate (FF)/GW642444 Inhalation Powder and the Individual Components Delivered Once Daily (AM) Via a Novel Dry Powder Inhaler Compared With Placebo in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Brief Summary: The Purpose of this study is to assess the efficacy and safety of two strengths of the FF/GW642444 Inhalation Powder in subject with Chronic Obstructive Pulmonary Disease (COPD)


Options:
A: Inclusion Criteria:

* Type of subject: outpatient
* Informed consent: Subjects must give their signed and dated written informed consent to participate.
* Gender: Male or female subjects A female is eligible to enter and participate in the study if she is of:
* Non-child bearing potential OR
* Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the acceptable contraceptive methods defined in the protocol
* 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 \[Celli, 2004\]
* Tobacco use: Subjects with a current or prior history of ≥10 pack-years of cigarette smoking at Screening (Visit 1).
* Severity of Disease: Subjects with a Screening (Visit 1) measured post-albuterol/salbutamol:
* FEV1/FVC ratio of ≤0.70 and
* FEV1 ≤70% of predicted normal values
* Dyspnea: Achieved a score of ≥2 on the Modified Medical Research Council Dyspnea Scale (mMRC) at Screening (Visit 1).

Exclusion Criteria:

Subjects meeting any of the following criteria must not be enrolled in the study:

* Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
* Asthma: Subjects with a current diagnosis of asthma
* α1-antitrypsin deficiency: Subjects with α1-antitrypsin deficiency as the underlying cause of COPD
* Other respiratory disorders: Subjects with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, 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 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.
* Hospitalization: Subjects who are hospitalized due to poorly controlled COPD within 12 weeks of Visit 1.
* Poorly controlled COPD: Subjects with poorly controlled COPD, defined as the occurrence of the following in the 6 weeks prior to Visit 1: Acute worsening of COPD that is managed by subject with 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 Visit 1.
* Other diseases/abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular (i.e., pacemaker), neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or haematological abnormalities that are uncontrolled.
* Peptic Ulcer disease: Subjects with clinically significant peptic ulcer disease that is uncontrolled.
* Hypertension: Subjects with clinically significant hypertension that is uncontrolled.
* 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.
* Drug/food allergy: Subjects with a history of hypersensitivity to any of the study medication or components of the inhalation powder
* 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 and/or their ipratropium 4 hours prior to spirometry testing at each study visit
* Additional medication: Use of certain medications such as bronchodilators and corticosteroids for the protocol-specified 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 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) device.
* 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.
* 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
* 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.
B: Inclusion Criteria:

1. Male or female patients with COPD according to GOLD 2011 who have signed informed consent.
2. Patients with airflow limitation of 30-80% post-bronchodilator FEV1 at run-in.
3. Current or ex-smokers with a smoking history of at least 10 pack years
4. Patients with a mMRC score of at least 2 at run-in.

Exclusion Criteria:

1. Patients contraindicated for muscarinic antagonist agents and beta-2 agonists
2. Patients with a history of malignancy of any organ system, treated or untreated, within the last five years
3. Patients with narrow-angle glaucoma, BPH or bladder-neck obstruction or moderate-severe renal impairment or urinary retention
4. Patients who had a COPD exacerbation within 6 weeks prior to screening.
5. Patients requiring long term oxygen therapy prescribed for more than 12 hr per day.
6. Patients with a history of asthma.
7. Patients with an onset of respiratory symptoms, including COPD diagnosis, prior to 40 years of age.
8. Patients with a blood eosinophil count of greater than 600 mm/3 during run-in
9. Patients with concomitant pulmonary disease
10. Patients with a history of certain cardiovascular co-morbid conditions
11. Patients with a diagnosis of alpha-1 anti-trypsin deficiency
12. Patients with active pulmonary tuberculosis
13. Patients in the active phase of a pulmonary rehabilitation programme
14. Other protocol-defined inclusion / exclusion criteria may apply
C: Inclusion Criteria:

* Diagnosis of moderate (as classified by the Global Initiative for Chronic Obstructive Lung Disease \[GOLD\] Guidelines, 2007) chronic obstructive pulmonary disease (COPD) and:

  1. Smoking history of at least 10 pack-years.
  2. Forced expiratory volume in 1 second (FEV1) \< 80% and ≥ 50% of the predicted normal value.
  3. Post-bronchodilator FEV1/Force vital capacity (FVC) \< 0.7.

Exclusion Criteria:

* Patients who have had a COPD exacerbation requiring systemic glucocorticosteroid treatment or antibiotics and/or hospitalization in the 6 weeks prior to screening.
* Patients who have had a respiratory tract infection within 6 weeks prior to screening.
* Patients with concomitant pulmonary disease.
* Patients with alpha-1-antitrypsin deficiency.
* Patients with contraindications for tiotropium treatment.
* Patients with a history of hypersensitivity to any of the study drugs or to drugs from similar drug classes.

Other protocol-defined inclusion/exclusion criteria applied to the study.
D: Inclusion Criteria:

* A male or female \>=40 years of age at Screening (Visit 1).
* Capable of giving written informed consent.
* Female subjects must be post-menopausal or using a highly effective method for avoidance of pregnancy.
* Subjects with a clinical history of COPD in accordance with the following definition by the American Thoracic Society/European Respiratory Society.
* Subject with a measured post-albuterol (salbutamol) FEV1/forced vital capacity(FVC) ratio of \<=0.70 at Screening.
* Subjects with a measured post-albuterol (salbutamol) FEV1 \<=70% of predicted normal values.
* Subjects with a current or prior history of ≥10 pack-years of cigarette smoking at Screening.

Exclusion Criteria:

* Current diagnosis of asthma. (Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD).
* Other respiratory disorders (alpha1-antitrypsin deficiency as the underlying cause of COPD, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, pulmonary fibrosis, pulmonary hypertension, interstitial lung diseases, or other active pulmonary diseases).
* Lung volume reduction surgery within the 12 months prior to Screening.
* Hospitalized due to poorly controlled COPD within 12 weeks of Screening.
* Poorly controlled COPD (occurrence of the following in the 6 weeks prior to Screening -Acute worsening of COPD that is managed by the subject with corticosteroids or antibiotics or that requires treatment prescribed by a physician).
* Lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to Screening.
* Moderate/severe COPD exacerbation/lower respiratory tract infection during Run-In Period.
* Abnormal and clinically significant 12-lead ECG at Screening
* Historical or current evidence of uncontrolled or clinically significant disease like cardiovascular, hypertension, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease), peptic ulcer disease, or haematological abnormalities. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
* History of hypersensitivity to any of the study medications or components of the inhalation powder; or history of severe milk protein allergy.
* Known or suspected history of alcohol or drug abuse within the last 2 years.
* Subjects who are medically unable to withhold their albuterol (salbutamol) and/or their ipratropium for the 4-hour period required prior to spirometry testing at each study visit.
* The subject has taken any other investigational drug within 30 days or 5 half-lives of the investigational product (IP) prior to the first dosing day in the current study.
* Use of additional medications prior to Screening (list of medications and time intervals are different for different class of medications and are indicated in the protocol)
* 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.
* Subjects who have participated in the acute phase of a Pulmonary Rehabilitation Program within 4 weeks prior to Screening
* Subjects at risk of non-compliance, or unable to comply with study procedures.
* 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.
* Women who are pregnant or lactating or are planning on becoming pregnant during the study.
* Previously randomized to either the HZC113109 or HZC112352 clinical studies.

Answer: A