Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Single Centre, Randomised, Placebo-controlled, Four-way Cross Over Study to Assess the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Single Inhaled Doses of GSK573719 and GW642444 as Monotherapies and Concurrently in Healthy Japanese Subjects
Brief Summary: GW642444 is a potent and selective long-acting beta2 agonist; GSK573719 is a long-acting, inhaled, muscarinic receptor antagonist (or anticholinergic) bronchodilator. Both are in development as once daily (QD) monotherapies for the treatment of Chronic Obstructive Pulmonary Disease (COPD). Development of these two inhaled drugs as a combination therapy is also planned and would have potential for improved efficacy and patient benefit as they both work through different receptor pathways and the combined bronchodilatory effect might be additive.

This study is a randomised, double blind, placebo-controlled, four-way crossover study which will assess the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of GSK573719 and GW642444 in sixteen healthy Japanese subjects. Subjects will receive four possible treatments as single inhaled doses, receiving the two monotherapies separately, the monotherapies concurrently, and placebo.

Blood samples for PK analysis will be taken at regular intervals after dosing. Safety will be assessed by measurement of heart rate, blood pressure, ECG and twenty-four hour Holter monitoring, potassium, safety laboratory data and review of adverse events.


Options:
A: 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
B: 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 or female subjects.
* 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, e.g., 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 following 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):
* Abstinence
* Oral Contraceptive, either combined or progestogen alone
* Injectable progestogen
* Implants of levonorgestrel
* Estrogenic vaginal ring
* Percutaneous contraceptive patches
* Intrauterine device (IUD) or intrauterine system (IUS) that meets the SOP effectiveness criteria as stated in the product label
* Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject. For this definition, "documented" refers to the outcome of the investigator's/designee's medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records.
* Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository)
* Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society.
* Smoking History: Current or former cigarette smokers with a history of cigarette smoking of \>=10 pack-years \[number of pack years = (number of cigarettes per day / 20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)\]. 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 FEV1/FVC ratio of \<0.70 and a pre and post-albuterol/salbutamol FEV1 of \<=70% of predicted normal values at Visit 1 (Screening) calculated using Nutrition Health and Examination Survey (NHANES) III reference equations.
* Dyspnea: A score of \>=2 on the mMRC Dyspnea Scale at Visit 1.
* QTc Criteria:
* QTc(F) \<450 milliseconds (msec) or
* QTc(F) \<480msec for patients with QRS duration \>=120msec
* The QTc is the QT interval corrected for heart rate according to either Bazett's formula (QTcB), Fridericia's formula (QTcF), or another method, machine or manual overread.
* For subject eligibility and withdrawal, QTcF will be used.
* For purposes of data analysis, QTcF will be used as primary.
* The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period.

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: Subjects with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled and/or a previous history of cancer in remission for \<5 years prior to Visit 1 (localized carcinoma of the skin that has been resected for cure is not exclusionary). 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.
* Contraindications: Any history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, sympathomimetic, corticosteroid (intranasal, inhaled or systemic) lactose/milk protein or magnesium stearate, or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction, that, in the opinion of the study physician contraindicates study participation or use of an inhaled Long acting muscarinic antagonist (LAMA), Long acting beta agonist (LABA) or Inhaled corticosteroids (ICS).
* Hospitalization: Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1.
* Lower respiratory tract infection: Subjects with lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to Visit 1.
* Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior to Visit 1.
* 12-Lead ECG: An abnormal and clinical significant ECG finding from the 12-lead ECG conducted at Visit 1. Investigators will be provided with ECG reviews conducted by a centralized independent cardiologist to assist in evaluation of subject eligibility. The study investigator will determine the medical significance of any ECG abnormalities.
* Clinically significant and abnormal laboratory finding at Screening (Visit1). After discussion with the Medical Monitor, the investigator may have the option to verify the abnormal lab result prior to Visit2
* Medication Prior to Spirometry: Unable to withhold albuterol/salbutamol for the 4 hour period required prior to spirometry testing at each study visit.
* Excluded Medications: Use of the following medications are not permitted within the defined time intervals prior to Visit 1and throughout the study:
* No use within 12 weeks prior to Screening Visit 1 or thereafter at any time during the study: Depot corticosteroids.
* No use within 6 weeks prior to Screening Visit 1 or thereafter at any time during the study: Systemic, oral or parenteral corticosteroids (Intra-articular corticosteroid injections are permitted.), Antibiotics (for lower respiratory tract infection), Cytochrome P450 3A4 strong inhibitors.
* No use within 14 days prior to Screening Visit 1 or thereafter at any time during the study: Phosphodiesterase 4 inhibitors (roflumilast).
* No use within 10 days prior to Screening Visit 1 or thereafter at any time during the study: Olodaterol and Indacaterol.
* No use within 7 days prior to Screening Visit 1 or thereafter at any time during the study: Long acting muscarinici antagonists (tiotropium, aclidinium, glycopyrronium).
* No use within 48 hrs prior to Screening Visit 1 or thereafter at any time during the study: Theophyllines, Oral leukotriene inhibitors (zafirlukast, montelukast, zileuton), Salmeterol and formoterol, ICS/LABA combinations (e.g., fluticasone propionate/salmeterol, mometasone furoate/formoterol fumarate, budesonide/formoterol fumarate), Oral beta2-agonists Long-acting.
* No use within 24 hrs prior to Screening Visit 1 or thereafter at any time during the study: Inhaled sodium cromoglycate or nedocromil sodium.
* No use within 12 hrs prior to Screening Visit 1 or thereafter at any time during the study: Oral beta2-agonists Short-acting.
* No use within 4 hrs prior to Screening Visit 1 or thereafter at any time during the study: Inhaled short acting beta2-agonists (use of study provided prn albuterol/salbutamol is permitted during the study, except in the 4-hour period prior to spirometry testing.), Inhaled short-acting anticholinergics, Inhaled short-acting anticholinergic/short-acting beta2-agonist combination products.
* No use within 30 days or 5 half lives whichever is longer prior to Screening Visit 1 or thereafter at any time during the study: Any other investigational drug.
* Prior enrolment in one of the replicate studies: subjects who have previously been assigned a subject number (enrolled) in study 200110 that is a replicate study of 200109.
* 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, 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.
* 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: A subject will not be eligible for this study if he/she is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.
* 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.
C: Inclusion Criteria:

* Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
* Japanese ethnic origin defined as having been born in Japan with four ethnic Japanese grandparents and able to speak Japanese.
* Male or female between 20 and 65 years of age inclusive, at the time of signing the informed consent.
* A female subject is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40 pg/ml (\<140 pmol/L) is confirmatory\].
* Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until completion of the follow-up visit.
* Body weight \> or equal to 45 kg and BMI within the range 18-28 kg/m2 inclusive.
* AST, ALT, alkaline phosphatase and bilirubin \< or equal to 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
* Average QTcB or QTcF \< 450 msec; or QTc \< 480 msec in subjects with Bundle Branch Block taken from triplicate assessments at screening.
* No clinically active and relevant abnormality on 12-lead ECG or 24h Holter ECG at screening.
* Normal spirometry (FEV1 ≥ 80% of predicted, FEV1/FVC ≥ 70%).
* Non-smokers (never smoked or not smoking for \>6 months with \<10 pack years history (Pack years = (cigarettes per day smoked/20) x number of years smoked))
* A signed and dated written informed consent is obtained from the subject
* The subject is capable of giving informed consent, which includes compliance with the requirements and restrictions listed in the consent form
* Available to complete the study

Exclusion Criteria:

* Any clinically important abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or ECG (12-lead). A 24hr Holter monitoring recording outside normal limits.
* 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 mean QTc(B) value at screening \>450msec, or an ECG that is not suitable for QT measurements (e.g. LBBB or poorly defined termination of the T wave).
* A history of elevated resting blood pressure or a mean blood pressure higher than 140/90 mmHg at screening.
* A mean heart rate outside the range 40-90 bpm at screening.
* The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates and benzodiazepines. The detection of drugs with a legitimate medical use would not necessarily be an exclusion to study participation. The detection of alcohol would not be an exclusion at screening but would need to be negative pre-dose and during the study.
* A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome).
* A positive test for HIV antibody.
* History of regular alcohol consumption within 3months of the study defined as:

an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). Under Australian guidelines, one standard unit defined as 10g of ethanol, is equivalent to 250ml of full-strength beer, 470 ml of light-strength beer, 100 ml of wine and 30ml of spirits.

* 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).
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
* Use of prescription or non-prescription drugs, including 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 GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
* History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
* Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
* Unwillingness or inability to follow the procedures outlined in the protocol. 17. Urinary cotinine levels indicative of smoking or history of regular use of tobacco- or nicotine-containing products prior to screening.
* The subject is unable to use the novel dry powder inhaler correctly.
* The subject has a known allergy or hypersensitivity to ipratropium bromide, tiotropium, atropine and any of its derivatives.
* Any adverse reaction including immediate or delayed hypersensitivity to any β2 agonist or sympathomimetic drug.
* The subject has a known allergy or hypersensitivity to milk protein or the excipients lactose monohydrate and MgSt.
* Subject is kept under regulatory of judicial order in an institution.
* Any female of childbearing potential.
* Subject is mentally or legally incapacitated.
D: Inclusion Criteria:

* Outpatient.
* A signed and dated written informed consent prior to study participation.
* Japanese subjects 40 years of age or older at Visit 1.
* Male or female subjects. A female is eligible if she is of: Non-child bearing potential or Child bearing potential agrees to one of the contraceptive methods.
* Subjects with a clinical history of COPD in accordance with the definition by COPD domestic guideline.
* Current or former cigarette smokers with a history of cigarette smoking of \>=10 pack-years at Visit 1.
* Subject with a measured post-salbutamol forced expiratory volume/forced vital capacity (FEV1/FVC) ratio of \<70% and Subjects with a measured post-salbutamol FEV1 \<80% of predicted normal values.

Exclusion Criteria (Visit 1):

* Women who are pregnant or lactating or are planning on becoming pregnant during the study.
* A current diagnosis of asthma.
* Known respiratory disorders other than COPD.
* Subjects with historical or current evidence of clinically significant abnormalities that are uncontrolled.
* A chest X-ray or computed tomography (CT) scan that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD.
* Allergy or hypersensitivity to muscarinic, beta2-agonist, lactose/milk protein or magnesium stearate or a condition that contraindicates participation.
* Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1.
* Subjects with lung volume reduction surgery within the 12 months prior to Screening (Visit 1).
* An abnormal and significant ECG finding from the 12-lead ECG conducted at Visit 1.
* Significantly abnormal finding from clinical chemistry or hematology, tests at Visit 1.
* Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed for greater than 12 hours a day.
* Regular use (prescribed every day, not for as-needed use) of short-acting bronchodilators (e.g., salbutamol) via nebulized therapy.
* Participation in the 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.
* Affiliation with Investigator Site.
* Previous use of GSK573719, the GSK573719/GW642444 combination.
* Use of any other investigational medication within 30 days or 5 drug half-lives (whichever is longer).

Exclusion Criteria (Visit 2):

- COPD Exacerbation during run-in period: Subject must not have experienced a COPD exacerbation or a lower respiratory tract infection during run-in or at Visit 2.

Answer: C