Please select the eligibility criteria that correspond to the clinical trial below.
Title: A12-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of GSK573719 Delivered Once-Daily Via a Novel Dry Powder Inhaler in Subjects With Chronic Obstructive Pulmonary Disease
Brief Summary: The purpose of this study is to assess if 12 weeks' treatment with GSK573719 Inhalation Powder is safe and effective compared with placebo or no active drug intake, when administered once-daily in subjects with Chronic Obstructive Pulmonary Disease (COPD).


Options:
A: Inclusion Criteria:

* Outpatient
* A signed and dated written informed consent prior to study participation.
* Male or female adults.
* 40 to 80 years of age at Visit 1
* Diagnosis of COPD
* Current or former cigarette smokers with a history of cigarette smoking of greater than or equal to 10 pack-years
* Post-albuterol forced expiratory volume in 1 second (FEV1)/ forced vital capacity (FVC)\<0.70 and post albuterol FEV1 of greater than or equal to 35% and less than or equal to 70% of predicted normal values

Exclusion Criteria:

* Women who are pregnant or lactating or are planning on becoming pregnant during the study.
* A current diagnosis of asthma
* Known alpha-1 antitrypsin deficiency, active lung infections (such as tuberculosis), and lung cancer
* Other significant respiratory conditions in addition to COPD
* Other diseases that are uncontrolled including cancer in remission for less than 5 years
* Chest x-ray or CT scan with clinically significant abnormalities not believed to be due to the presence of COPD
* Hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate
* A medical condition that contraindicates study participation or use of an inhaled anticholinergic
* Hospitalization for COPD or pneumonia within 12 weeks of Visit 1
* Any previous lung resection surgery
* A body mass index (BMI) value of \>35 kilogram (kg)/meter squared (m2)
* An abnormal and significant electrocardiogram finding at Visit 1
* Significantly abnormal finding from clinical chemistry or haematology tests at Visit 1.
* A positive Hepatitis B surface antigen or positive Hepatitis C antibody
* Medically unable to withhold albuterol (salbutamol) for the 6 hour period prior to study visits
* Use of depot corticosteroids within 12 weeks of Visit 1
* Use of oral or parenteral corticosteroids or antibiotics for lower respiratory tract infection within 6 weeks of Visit 1
* Use of long-acting beta-agonist (LABA)/inhaled corticosteroid (ICS) product if LABA/ICS therapy is discontinued within 30 days of Visit 1
* Use of ICS at a dose of \>1000mcg/day of fluticasone propionate or equivalent within 30 days of Visit 1
* Initiation or discontinuation of ICS within 30 days of Visit 1
* Use of tiotropium or phosphodiesterase 4 inhibitors within 14 days of Visit 1
* Use of theophyllines, oral leukotriene inhibitors, long-acting oral beta-agonists, or inhaled long-acting beta-agonists within 48 hours of Visit 1
* Short-acting oral beta-agonists within 12 hours of Visit 1
* Use of LABA/ICS combination products only if discontinuing LABA therapy and switching to ICS monotherapy within 48 hours of Visit 1 for the LABA component
* Use of sodium cromoglycate or nedocromil sodium within 24 hours of Visit 1
* Use of inhaled short-acting beta-agonists, inhaled short-acting anticholinergics, or inhaled short-acting anticholinergic/short-acting beta-agonist combination products within 6 hours of Visit 1
* Use of any other investigational medication within 30 days or 5 drug half-lives (whichever is longer)
* Oxygen therapy prescribed for greater than 12 hours a day
* Regular use (prescribed for use every day, not for as-needed use) of short-acting bronchodilators
* Use of continuous positive airway pressure (CPAP), nocturnal positive pressure or non-invasive positive pressure ventilation (NIPPV), including use for sleep apnea.
* Acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1
* A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1
* Anyone affiliated with investigator site
* Previous use of GSK573719 or GSK53719/GW642444
B: Inclusion Criteria:

* Healthy male or females at ratio of 1:1, aged 18 - 45 years . Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
* Body weight ≥ 50kg and body mass index (weight/height2) within the range of 19 - 24 kg/m2, inclusive.
* Male or female subjects at the time of signing the informed consent:
* Female subject who is child-bearing potential should agree to use one of the contraception methods (contraceptives intrauterine device, implantable progesterone device or oral contraceptive) for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. The subjects must agree to use contraception until completion of the follow-up visit.
* Male subjects have to agree to use one of the contraception methods listed in Section 8.1.2. This criterion is to be followed from the time of the first dose of study medication until completion of the follow-up visit
* Normal systolic (90-139mmHg) and diastolic (60-89mmHg) blood pressure at pre-study screening.
* Subjects who are current non-smokers, who have not used any tobacco products in the 6 month period preceding the screening visit, and have a pack history of 10 pack years. (pack years = (cigarettes per day smoked/20) × number of years smoked)).
* No significant abnormality on 12-lead ECG at screening, QTcF interval must be \<450msec (QTcF; machine or manual reading).
* AST (SGOT), ALT (SGPT), and total-bilirubin 1.5xULN at screening. No significant clinical abnormality on other laboratory tests.
* Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
* Subjects who are able to use the inhalation device satisfactorily

Exclusion Criteria:

* As a result of medical interview, physical examination or screening investigations, the principle investigator or delegate physician deems the subject unsuitable for the study.
* History of mental, cardiac, renal, hepatic, significant gastrointestinal or respiratory disease as judged by the investigator
* A history of breathing problems (i.e. history of asthmatic symptomatology, unless asthma in childhood that has now resolved and no longer requires maintenance therapy which should not be an exclusion).
* A chest X-ray or computed tomography (CT) scan that reveals evidence of clinically significant abnormalities. A chest X-ray must be taken at day -1 of the first treatment if a chest X-ray or CT scan is not available within 6 months prior to that day.

History of sensitivity to heparin, heparin-induced thrombocytopenia, or sensitivity to any of the study medications, or components thereof, known allergy or hypersensitivity to milk protein or the excipients lactose monohydrate and magnesium stearate (MgSt), or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.

* The subject has taken prescription or non-prescription drugs, including CYP3A/PGP inhibitor, vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and Sponsor the medication will not interfere with the study procedures or compromise subject safety.
* Positive result of urine cotinine test.
* The subject has a history of cholecystectomy or biliary tract disease.
* The subject has a significant clinical history or current conditions of glaucoma.
* The subject has a significant clinical history or current conditions of prostatic hypertrophy.
* The subject has a positive pre-study drug screen. A minimum list of drugs that were screened for included amphetamines, barbiturates, cocaine, opiates and benzodiazepines. The detection of drugs with a legitimate medical use was not necessarily an exclusion to study participation. The detection of alcohol was not an exclusion at screening but had to be negative pre-dose and during the study.
* History of regular alcohol consumption within 3 months of the study defined as:
* Abuse of an average weekly intake of greater than 21 units or an average daily intake of greater than three units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than two units (females). One unit was equivalent to a half-pint (220 mL) of beer or one (25 mL) measure of spirits or one glass (125 mL) of wine.
* Female subjects, who are pregnant, planned pregnancy or lactation.
* The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
* Blood donation or sampled as a study subject within three months preceding the first dose of study drug and blood donation during the entire study in excess of 500mL.
* A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
* The subject has tested positive for HIV antibodies.
* Unwillingness or inability to follow the procedures outlined in the protocol.
* Subject is mentally or legally incapacitated.
C: Inclusion Criteria:

* Type of subject: outpatient
* Informed Consent: a signed and dated written informed consent prior to study participation
* Age: subjects 40 years of age or older at Visit 1.
* Gender: male and female subjects are eligible to participate in the study. A female is eligible to enter and participate in the study if she is of: Non-child bearing potential i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile. Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, eg, age appropriate, \> 45 years, in the absence of hormone replacement therapy OR child bearing potential, has a negative pregnancy test at screening, and agrees to one of the acceptable contraceptive methods used consistently and correctly i.e., in accordance with the approved product label and the instructions of the physician for the duration of the study - screening to follow-up contact.
* Diagnosis: an established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society (ERS)
* Smoking history: current or former cigarette smokers with a history of cigarette smoking of \>= 10 pack-years \[number of pack years = (number of cigarettes per day / 20) x number of years smoked (eg. 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years both equal 10 pack-years)\]. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. Pipe and/or cigar use cannot be used to calculate pack-year history
* Severity of Disease: A pre and post-albuterol/salbutamol forced expiratory volume in one second/ forced vital capacity (FEV1/FVC ratio of \<0.70 and a post-albuterol/salbutamol FEV1 of \>=30% and =\<70% of predicted normal values at Visit 1. Predicted values will be based upon the ERS Global Lung Function Initiative
* Dyspnea: A score of \>=2 on the modified medical research council dyspnea scale (mMRC) at Visit 1

Exclusion Criteria:

* Pregnancy: women who are pregnant or lactating or are planning on becoming pregnant during the study.
* Asthma: a current diagnosis of asthma.
* Other respiratory disorders: known alpha-1 antitrypsin deficiency, active lung infections (such as tuberculosis), and lung cancer are absolute exclusionary conditions. A subject who, in the opinion of the investigator, has any other significant respiratory conditions in addition to COPD should be excluded. Examples may include clinically significant bronchiectasis, pulmonary hypertension, sarcoidosis, or interstitial lung disease.
* Other diseases/abnormalities: any subject who is considered unlikely to survive the duration of the study period or has any rapidly progressing disease or immediate life-threatening illness (e.g. cancer). In addition, any subject who has any condition (e.g. neurological condition) that is likely to affect respiratory function should not be included in the study.
* Severe hepatic impairment: patients with severe hepatic impairment (Child-Pugh class C) should be excluded unless, in the opinion of the investigator, the benefit is likely to outweigh the risk.
* Severe renal impairment: patients with severe renal impairment (e.g., end-stage renal disease requiring dialysis) should be excluded, unless in the opinion of the investigator, the benefit is likely to outweigh the risk.
* Unstable or life threatening cardiac disease: long-acting muscarinic antagonists (LAMA) should be used with caution in subjects with severe cardiovascular disease. In the opinion of the investigator, use should only be considered if the benefit is likely to outweigh the risk in conditions such as: Myocardial infarction or unstable angina in the last 6 months, Unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months, New York Heart Association (NYHA) Class IV heart failure
* Contraindications: Any history of allergy or hypersensitivity to any anticholinergic/ muscarinic receptor antagonist, sympathomimetic, lactose/milk protein or magnesium stearate.
* Antimuscarinic effects: Subjects with medical conditions such as narrow-angle glaucoma, urinary retention, prostatic hypertrophy, or bladder neck obstruction should only be included if, in the opinion of the study physician, the benefit outweighs the risk.
* Hospitalization: hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1.
* Lung resection: lung volume reduction surgery within the 12 months prior to Visit 1.
* 12-Lead electrocardiogram (ECG): Investigators will be provided with ECG reviews conducted by a centralized independent cardiologist to assist in evaluation of subject eligibility. The Investigator will determine the clinical significance of each abnormal ECG finding in relation to the subject's medical history and exclude subjects who would be at undue risk by participating in the trial. Subjects with the following abnormalities are excluded from participation in the study: Atrial fibrillation with rapid ventricular rate \>120 beats per minute; sustained or nonsustained ventricular tachycardia; second degree heart block Mobitz type II or third degree heart block (unless pacemaker or defibrillator had been inserted)
* Medication prior to spirometry: unable to withhold albuterol/salbutamol for the 4 hour period required prior to spirometry testing at each study visit.
* Medications prior to screening: use of the following medications according to the following defined time intervals prior to Visit 1: depot corticosteroids 12 weeks, systemic, oral or parenteral corticosteroids 6 weeks, antibiotics (for lower respiratory tract infection) 6 weeks, inhaled long acting beta2 agonists/ inhaled corticosteroid (LABA/ICS) combination products if LABA/ICS therapy is discontinued completely 30 days; LABA/ICS combination products only If discontinuing ICS/ LABA therapy and switching to ICS monotherapy 48 hours for the salmeterol or formoterol component 14 days for the vilanterol component (note: the dose of ICS must be a dose of fluticasone propionate (FP) or equivalent but not to exceed 1000 mcg/day), use of ICS at a dose \>1000 microgram (mcg)/day of FP or equivalent 30 days (note: use of ICS is permitted provided the dose does not exceed 1000 mcg of FP or equivalent; ICS use not to be initiated or discontinued within 30 days prior to Visit 1, except for subjects on LABA/ICS therapy who may discontinue the ICS/LABA product as indicated in the table above and switch to ICS monotherapy); initiation or discontinuation of ICS use 30 days (note: use of ICS is permitted provided the dose does not exceed 1000 mcg of FP or equivalent; ICS use not to be initiated or discontinued within 30 days prior to Visit 1, except for subjects on LABA/ICS therapy who may discontinue the ICS/LABA product as indicated in the table above and switch to ICS monotherapy); phosphodiesterase 4 (PDE4) Inhibitor (roflumilast) 14 days; LABA: salmeterol and formoterol 48 hours; olodaterol, indacaterol, and vilanterol 14 days; LAMA: tiotropium, aclidinium, glycopyrronium, umeclidinium 7 days; LAMA/LABA combination products if LAMA/LABA therapy is discontinued completely then apply whichever mono component has the longest washout; theophyllines 48 hours; Oral beta2-agonists: long-acting 48 hours, short-acting 12 hours; inhaled short acting beta2-agonists 4 hours (note: use of study provided albuterol/salbutamol is permitted during the study, except in the 4-hour period prior to spirometry testing); inhaled short-acting anticholinergics 4 hours; inhaled short-acting anticholinergic/short-acting beta2-agonist combination products 4 hours; any other investigational medication 30 days or within 5 drug half-lives (whichever is longer).
* Oxygen: use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed for greater than 12 hours a day. As-needed oxygen use (i.e. =\<12 hours per day) is not exclusionary.
* Nebulized therapy: regular use (prescribed for use every day, not for as-needed use) of short-acting bronchodilators (e.g. albuterol/salbutamol) via nebulized therapy.
* Pulmonary rehabilitation program: participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.
* Drug or alcohol abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1.
* Affiliation with investigator site: is an investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the aforementioned that is involved in this study.
* Inability to read: in the opinion of the investigator, any subject who is unable to read and/or would not be able to complete a questionnaire
D: Inclusion Criteria:

* Diagnosis of COPD
* 10 pack-year or greater history of cigarette smoking
* Post-bronchodilator FEV1/FVC of \<0.7
* Predicted FEV1 of 70% of normal or less
* Modified Medical Research Council (mMRC) dyspnea score of 2 or greater

Exclusion Criteria:

* Women who are pregnant, lactating, or planning to become pregnant
* Respiratory disorders other than COPD, including a current diagnosis of asthma
* Clinically significant non-respiratory diseases or abnormalities that are not adequately controlled
* Significant allergy or hypersensitivity to anticholinergics, beta2-agonists, or the excipients of magnesium stereate or lactose used in the inhaler delivery device
* Hospitalization for COPD or pneumonia within 12 weeks prior to screening
* Lung volume reduction surgery within 12 weeks prior to screening
* Abnormal and clinically significant ECG findings at screening
* Clinically significant laboratory findings at screening
* Use of systemic corticosteroids, antibiotics for respiratory tract infections, high dose inhaled steroids (\>1000mcg fluticasone propionate or equivalent), PDE4 inhibitors, tiotropium, oral beta2-agoinists, short- and long-acting inhaled beta2-agonists, inhaled sodium cromoglycate or nedocromil sodium, or investigational medicines for defined time periods prior to the screening visit
* Use of long-term oxygen therapy (12 hours or greater per day)
* Regular use of nebulized treatment with short-acting bronchodilators
* Participation in the acute phase of a pulmonary rehabilitation program
* A know or suspected history of alcohol or drug abuse
* Affiliation with the investigational site
* Previous use of GSK573719 or the combination of GSK573719/GW642444

Answer: D