Dose-Finding Study of Batefenterol (GSK961081) Via Dry Powder Inhaler in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Inclusion Criteria:

- Type of subject: Outpatient

- Informed Consent: A signed and dated written informed consent prior to study
participation

- Age: 40 years of age or older at Visit 1.

- Gender: Male and female subjects are eligible to participate in the study. Female
subjects are eligible to participate if not pregnant (as confirmed by a negative urine
human chorionic gonadotrophin [hCG] test), not lactating, and at least one of the
following conditions applies:

Non-reproductive potential defined as:

Pre-menopausal females with one of the following: Documented tubal ligation Documented
hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal
occlusion Hysterectomy Documented Bilateral Oophorectomy Postmenopausal defined as 12
months of spontaneous amenorrhea. Females on hormone replacement therapy (HRT) and whose
menopausal status is in doubt will be required to use one of the highly effective
contraception methods if they wish to continue their HRT during the study. Otherwise, they
must discontinue HRT to allow confirmation of postmenopausal status prior to study
enrolment.

Reproductive potential and agrees to follow one of the options listed below 30 days prior
to the first dose of study medication and until at least five terminal half-lives OR until
any continuing pharmacologic effect has ended, whichever is longer after the last dose of
study medication and completion of the follow-up visit. This list does not apply to females
of reproductive potential with same sex partners, when this is their preferred and usual
lifestyle or for subjects who are and will continue to be abstinent from penile-vaginal
intercourse on a long term and persistent basis.

Contraceptive subdermal implant that meets <1 percent (%) rate of failure per year, as
stated in the product label Intrauterine device or intrauterine system that meets <1% rate
of failure per year, as stated in the product label Oral Contraceptive, either combined or
progestogen alone Injectable progestogen Contraceptive vaginal ring Percutaneous
contraceptive patches Male partner sterilization with documentation of azoospermia prior to
the female subjects entry into the study, and this male is the sole partner for that
subject These allowed methods of contraception are only effective when used consistently,
correctly and in accordance with the product label. The investigator is responsible for
ensuring that subjects understand how to properly use these methods of contraception.

- Diagnosis: An established clinical history of COPD in accordance with the definition
by the American Thoracic Society/European Respiratory Society as follows: Chronic
obstructive pulmonary disease is a preventable and treatable disease state
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.

- Smoking History: Current or former cigarette smokers with a history of cigarette
smoking of >=10 pack-years. Former smokers are defined as those who have stopped
smoking for at least 6 months prior to Visit 1. 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 both equal 10 pack-years). Note: pipe and
cigar cannot be used to calculate pack-year history.

- Severity of Disease: A post-albuterol/salbutamol FEV1/FVC ratio of <=0.70 and a
post-albuterol/salbutamol FEV1 >=30 and <=70% of predicted normal at Visit 1.

Note: Percent predicted will be calculated using the European Respiratory Society Global
Lung Function Initiative reference equations.

Exclusion Criteria:

- 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: Known respiratory disorders other than COPD including but
not limited to alpha-1 antitrypsin deficiency, active tuberculosis, bronchiectasis,
sarcoidosis, lung fibrosis, pulmonary hypertension unrelated to COPD, and interstitial
lung disease. Allergic rhinitis is not exclusionary.

- Other Diseases/Abnormalities: Any significant diseases (including uncontrolled
hypertension, diabetes and thyroid disease) that in the opinion of the investigator or
the study medical monitor would put the safety of the subject at risk through study
participation, or which would affect study analyses if the diseases/condition
exacerbated during the study.

- Hepatitis: Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C
antibody test result at screening Visit 1 or within 3 months prior to first dose of
study treatment. (subjects with positive hepatitis C antibody due to prior resolved
disease can be enrolled only if a confirmatory negative Hepatitis C ribonucleic acid
(RNA) polymerase chain reaction (PCR) test is obtained).

- Liver Disease: Current or chronic history of liver disease, known hepatic or biliary
abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

- Cancer: A current malignancy or previous history of cancer in remission for <5 years
prior to Visit 1 (localised basal cell or squamous cell carcinoma of the skin that has
been resected is not exclusionary.) Any current or previous history of throat cancer.

- Chest X-Ray: 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. A
chest X-ray must be taken at Visit 1 if a chest X-ray or CT scan is not available
within 6 months prior to Visit 1. For subjects in Germany, if a chest X-ray (or CT
scan) is not available in the 6 months prior to Visit 1 the subject will not be
eligible for the study.

- Drug Allergy: A history of hypersensitivity or allergy to any beta adrenergic
receptor-agonist, sympathomimetic, anticholinergic/anti-muscarinic receptor
antagonist, or lactose/milk protein, which in the opinion of the investigator or
GlaxoSmithKline (GSK) medical monitor contraindicates study participation.

- Diseases Preventing Use of Anticholinergic: Medical diagnosis of narrow- angle
glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the
study investigator would prevent use of an inhaled anticholinergic.

- Poorly controlled COPD: defined as the occurrence of 'acute worsening of COPD that is
managed with corticosteroid and/or antibiotics or that requires treatment prescribed
by a physician in the 6 weeks prior to Screening (Visit 1), or 'subjects who are
hospitalized due to acute worsening of COPD within 12 weeks of Visit 1.

- History of COPD exacerbation: Subjects who have had more than one exacerbation
(moderate or severe) within the 12 months prior to Visit 1.

- Pneumonia and lower respiratory tract infection: Subjects with lower respiratory tract
infection that required the use of antibiotics within 6 weeks prior to Visit 1 or
subjects hospitalized due to pneumonia within 12 weeks of Visit 1.

- Lung Resection: Lung volume reduction surgery within the 12 months prior to Visit 1.

- 12-lead ECG: An abnormal and clinically significant 12-lead electrocardiogram (ECG).
Site investigators will be provided with ECG over-read conducted by a centralized
independent cardiologist, to assist in evaluation of subject eligibility. For this
study, an abnormal and clinically significant ECG that would preclude a subject from
entering the trial is defined as a 12-lead tracing that is interpreted as, but not
limited to the criteria mentioned in the protocol.

- Screening Labs: Clinically significant abnormal finding from clinical chemistry or
hematology tests at Visit 1.

- Medication Prior to Spirometry: Unable to with hold 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 1 and throughout the study: depot
corticosteroids (12 weeks), antibiotics (for lower respiratory tract infection) (6
weeks), cytochrome P450 3A4 strong inhibitors and P-glycoprotein inhibitors (4 weeks),
systemic, oral or parenteral corticosteroids (2 weeks), inhaled corticosteroids (ICS)
or long-acting beta2- agonist (LABA)/ ICS combination products (2 weeks),
phosphodiesterase 4 (PDE4) inhibitor (roflumilast) (2 weeks), LABA/ long acting
muscarinic receptor antagonist (LAMA) combination (eg vilanterol /umeclidinium
bromide) (2 weeks), Once-daily beta2-agonist ( eg Olodaterol and Indacaterol) (10
days), long acting muscarinic antagonists (eg tiotropium, aclidinium, glycopyrronium,
umeclidinium) (7 days), theophyllines (48 h), oral leukotriene inhibitors
(zafirlukast, montelukast, zileuton) (48 h), oral beta2-agonists long-acting (48 h),
short-acting (12 h), inhaled long acting beta2-agonists (LABA, e.g. salmeterol,
formoterol, indacaterol) (48 h), inhaled sodium cromoglycate or nedocromil sodium (24
h), inhaled short acting beta2-agonists (4 h), inhaled short-acting anticholinergics
(4 h), inhaled short-acting anticholinergic/ short-acting beta2-agonist combination
products (4 h), any other investigational medication (30 days or within 5 drug
half-lives [whichever is longer]).

The complete list of excluded cytochrome P450 inhibitors and P-glycoprotein inhibitors will
be provided in study reference manual (SRM).

Use of study provided albuterol/salbutamol is permitted during the study, except in the
4-hour period prior to spirometry testing.

- Oxygen: Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed
for greater than 12 h a day. As-needed oxygen use (i.e. <=12 h 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.

- 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

- 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 diary.