An Efficacy Study of Umeclidinium/Vilanterol With Tiotropium/Olodaterol in COPD Patients

Inclusion Criteria:

- Outpatients of either sex, 40 years of age or older at Visit 1, and with a diagnosis
of chronic obstructive pulmonary disease (COPD) defined by the American Thoracic
Society/European Respiratory Society (ERS)

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

- A female is eligible to enter and participate in the study if she is not pregnant (as
confirmed by a negative urine human chorionic gonadotrophin [hCG] test); not
lactating; and of non-reproductive potential (i.e., physiologically incapable of
becoming pregnant, including any female who is post-menopausal or surgically sterile),
which is defined as pre-menopausal females with one of the following: documented tubal
ligation; documented hysteroscopic tubal occlusion procedure with follow-up
confirmation of bilateral or tubal occlusion ; hysterectomy; documented bilateral
oophorectomy.

Postmenopausal is defined as 12 months of spontaneous amenorrhea in questionable cases a
blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels
consistent with menopause (refer to laboratory reference ranges for confirmatory levels).
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 post-menopausal status prior to study enrolment OR

- A female of reproductive potential, has a negative pregnancy test at screening, and
agrees to one of the methods below in the GSK Modified List of Highly Effective
Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements
from methods used consistently and correctly (i.e., in accordance with the local
approved product label and per study investigator discretion and the instructions of
the physician from 30 days prior to the first dose of study medication and until to
follow-up contact):

GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in FRP (this list does
not apply to FRP 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 the standard operating procedure (SOP)
effectiveness criteria including a <1% rate of failure per year, as stated in the
product label

- Intrauterine device or intrauterine system that meets the SOP effectiveness criteria
including a <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
subject's 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

- 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. Pipe and/or cigar use cannot be used to calculate pack-year
history.

- A pre and post-albuterol/salbutamol forced expiratory volume in one second
(FEV1)/Forced Vital Capacity ratio of <0.70 and a post-albuterol/salbutamol FEV1 of
<=70% to >=50 % of predicted normal values at Visit 1. Predicted values will be based
upon the ERS' Global Lung Function Initiative

- A score of >=2 on the Modified Medical Research Council Dyspnea Scale at Visit 1

Exclusion Criteria:

- Women who are pregnant or lactating or are planning on becoming pregnant during the
study

- A current diagnosis of asthma

- Subjects with alpha-1 antitrypsin deficiency as the underlying cause of COPD

- Subjects with active tuberculosis are excluded. Subjects with other respiratory
disorders (e.g. clinically significant: bronchiectasis, sarcoidosis, lung fibrosis,
pulmonary hypertension, interstitial lung diseases) are excluded if these conditions
are the primary cause of their respiratory symptoms.

- 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 other condition (e.g. neurological
condition) that is likely to affect respiratory function should not be included in the
study

- Current active liver or biliary disease (with the exception of Gilbert's syndrome or
asymptomatic gallstones or otherwise stable chronic liver disease per investigator
assessment

- Investigational Product 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
Class IV heart failure

- Any history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor
antagonist, sympathomimetic, lactose/milk protein or magnesium stearate

- Subjects with medical conditions such as narrow-angle glaucoma, urinary retention,
prostatic hypertrophy, or bladder neck obstruction should be excluded unless, in the
opinion of the study physician, the benefit outweighs the risk

- Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1. Pneumonia
and/or moderate or severe COPD exacerbation that has not resolved at least 14 days
prior to Screening (V1) and at least 30 days following the last dose of oral/systemic
corticosteroids (if applicable).

- Other respiratory tract infections that have not resolved at least 7 days prior to
Screening (V1).

- Subjects with lung volume reduction surgery (including procedures such as
endobronchial valves) within the 12 months prior to Screening (V1).

- The Investigator will determine the clinical significance of each abnormal
electrocardiogram finding in relation to the subject's medical history and exclude
subjects who would be at undue risk by participating in the trial

- Unable to withhold albuterol/salbutamol for the 4-hour (h) period required prior to
spirometry testing at each study visit

- Use of the pre-defined medications according to the pre-defined defined time intervals
prior to Screening (Visit 1)

- Use of long-term oxygen therapy described as resting oxygen therapy >3 liter
(L)/minute (min) at screening. (Oxygen use <=3 L/min flow is not exclusionary, and
patients may adjust oxygen levels as needed during the study.)

- Regular use (prescribed for daily/ regular use, not for as-needed use) of short-acting
bronchodilators (e.g. albuterol/salbutamol).

- Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks
prior to Screening (Visit 1). Subjects who are in the maintenance phase of a pulmonary
rehabilitation program are not excluded

- A known or suspected history of alcohol or drug abuse within 2 years prior to
Screening (Visit 1) that in the opinion of the investigator would prevent the subject
from completing the study procedures

- 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

- In the opinion of the investigator, any subject who is unable to read and/or would not
be able to complete a questionnaire.