A Comparative Study Between Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) Single Inhaler Triple Therapy Versus Tiotropium Monotherapy in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Inclusion Criteria:

- Subjects capable of giving signed informed consent.

- Outpatients will be included in the study.

- Subjects 40 years of age or older at Screening (Visit 1).

- Male or female subjects will be included; a female subject is eligible to participate
if she is not pregnant, not breastfeeding, and at least one of the following
conditions applies: not a woman of childbearing potential (WOCBP) or a WOCBP who
agrees to follow the contraceptive guidance during the treatment period and until the
safety follow-up contact after the last dose of study treatment.

- An established clinical history of COPD in accordance with the definition by the
American Thoracic Society/European Respiratory Society.

- Current or former cigarette smokers with a history of cigarette smoking of >=10
pack-years at Screening (Visit 1) (number of pack years = [number of cigarettes per
day / 20] x number of years smoked [example given {e.g.}, 20 cigarettes per day for 10
years, or 10 cigarettes per day for 20 years]). Previous smokers are defined as those
who have stopped smoking for at least 6 months prior to Visit 1.

- A score of >=10 on the COPD Assessment Test (CAT) at Screening (Visit 1).

- Subjects must demonstrate at Screening: A post-bronchodilator FEV1 <50 percent
predicted normal or a post-bronchodilator FEV1 <80 percent predicted normal and a
documented history of >=2 moderate exacerbations or one severe (hospitalized)
exacerbation in the previous 12 months. Subjects must also have a measured post
albuterol/salbutamol FEV1/forced vital capacity (FVC) ratio of <0.70 at screening.

- Subjects must have been receiving daily maintenance treatment with tiotropium alone
(via the HANDIHALER or RESPIMAT®) for their COPD for at least 3 months prior to
Screening.

Exclusion Criteria:

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

- Subjects with a current diagnosis of asthma. (Subjects with a prior history of asthma
are eligible if they have a current diagnosis of COPD).

- Subjects with alpha1-antitrypsin deficiency as the underlying cause of COPD.

- Subjects with active tuberculosis, lung cancer, and clinically significant:
bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung
disease or other active pulmonary diseases.

- Subjects who have undergone lung volume reduction surgery within the 12 months prior
to Screening.

- Immune suppression (e.g. advanced human immunodeficiency virus [HIV] with high viral
load and low cluster of differentiation 4 [CD4] count, lupus on immunosuppressant's)
that in the opinion of the investigator would increase risk of pneumonia or other risk
factors for pneumonia (e.g. neurological disorders affecting control of the upper
airway, such as Parkinson's Disease, Myasthenia Gravis). Subjects at potentially high
risk for pneumonia (e.g. very low body mass index [BMI], severely malnourished, or
very low FEV1) will only be included at the discretion of the Investigator.

- Pneumonia and/or moderate or severe COPD exacerbation that has not resolved at least
14 days prior to Screening and at least 30 days following the last dose of
oral/systemic corticosteroids (if applicable).

- Respiratory tract infection that has not resolved at least 7 days prior to Screening.

- Chest x-ray (posteroanterior and lateral) reveals evidence of pneumonia or a
clinically significant abnormality not believed to be due to the presence of COPD, or
another condition that would hinder the ability to detect an infiltrate on chest x-ray
(e.g. significant cardiomegaly, pleural effusion or scarring). All subjects will have
a chest x-ray at Screening Visit 1 (or historical radiograph or computerized
tomography [CT] scan obtained within 3 months prior to screening). For sites in
Germany: If a chest x-ray (or CT scan) within 3 months prior to Screening (Visit 1) is
not available, approval to conduct a diagnostic chest x-ray will need to be obtained
from the Federal Office for Radiation Protection (BfS).

- Subjects with historical or current evidence of clinically significant cardiovascular,
neurological, psychiatric, renal, hepatic, immunological, gastrointestinal,
urogenital, nervous system, musculoskeletal, skin, sensory, endocrine (including
uncontrolled diabetes or thyroid disease) or hematological abnormalities that are
uncontrolled. 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.

- Alanine Transaminase (ALT) >2x Upper Limit of Normal (ULN); and bilirubin >1.5x ULN
(isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct
bilirubin <35 percent). 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). Chronic stable hepatitis B and C (e.g., presence
of hepatitis B surface antigen [HBsAg] or positive hepatitis C antibody test result at
screening or within 3 months prior to first dose of study treatment) are acceptable if
subject otherwise meets entry criteria.

- Subjects with any of the following at Screening (Visit 1): 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.

- Abnormal and clinically significant 12-lead electrocardiogram (ECG) finding at Visit
1. 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. An abnormal and clinically significant
finding that would preclude a subject from entering the trial is defined as a 12-lead
ECG tracing that is interpreted at, but not limited to, any of the following: atrial
fibrillation (AF) with rapid ventricular rate >120 beats per minute (BPM); sustained
and non-sustained ventricular tachycardia (VT); second degree heart block Mobitz type
II and third degree heart block (unless pacemaker or defibrillator had been inserted);
QT interval corrected for heart rate (QTc) >=500 millisecond (msec) in subjects with
QRS <120 msec and QTc >=530 msec in subjects with QRS >=120 msec.

- A history of allergy or hypersensitivity to any corticosteroid,
anticholinergic/muscarinic receptor antagonist, beta2-agonist, 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 Investigator,
contraindicates study participation.

- Subjects with carcinoma that has not been in complete remission for at least 3 years.
Subjects who have had carcinoma in situ of the cervix, squamous cell carcinoma and
basal cell carcinoma of the skin would not be excluded based on the 3 year waiting
period if the subject has been considered cured by treatment.

- Use of long-term oxygen therapy (LTOT) described as resting oxygen therapy >3 Liters
per minute (L/minute) (Oxygen use <=3 L/minute flow is not exclusionary.)

- Subjects who are medically unable to withhold their albuterol/salbutamol for the
4-hour period required prior to spirometry testing at each study visit.

- Subjects who have participated in the acute phase of a Pulmonary Rehabilitation
Programme within 4 weeks prior to screening or subjects who plan to enter the acute
phase of a Pulmonary Rehabilitation Programme during the study. Subjects who are in
the maintenance phase of a Pulmonary Rehabilitation Programme are not excluded.

- Subjects with a known or suspected history of alcohol or drug abuse within the last 2
years.

- 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.

- 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.

- Study Investigators, sub-Investigators, study coordinators, employees of a
participating Investigator or study site, or immediate family members of the
aforementioned that is involved with this study.

- In the opinion of the Investigator, any subject who is unable to read and/or would not
be able to complete study related materials.

- Subjects taking following drug therapies will be excluded; subjects taking inhaled
short-acting anticholinergics alone or along with short-acting beta agonist
combination within 6 hours prior to screening; subjects taking inhaled short-acting
beta2 agonists within >=4 hours prior to screening; subjects taking ICS, ICS/inhaled
LABA combinations (e.g., FF/salmeterol, mometasone furoate/formoterol fumarate,
budesonide/formoterol fumarate; FF/VI), Phosphodiesterase 4 (PDE4) inhibitors
(roflumilast), LABA (e.g., indacaterol, olodaterol), LAMA (e.g., LAMA/LABA
combinations UMEC, aclidinium, glycopyrronium), LAMA/LABA combinations, theophyllines,
sodium cromoglycate and nedocromil sodium, anti-leukotrienes as maintenance treatment
within 3 months prior to Visit 1 will be excluded. Maintenance treatment is defined as
use for >=14 consecutive days (at any time in the 3 months prior to Visit 1). Subjects
taking long term antibiotic therapy. (Antibiotics are allowed for the short term
treatment (<=14 days) of an exacerbation or for short term treatment (<=14 days) of
other acute infections during the study); subjects taking systemic, oral, parenteral
corticosteroids 30 days prior to screening; (During the study oral/systemic
corticosteroids may be used for <=14 days to treat COPD exacerbations/pneumonia) will
be excluded. Intra-articular injections are allowed; subjects taking any other
investigational drug within 30 days or 5 half-lives whichever is longer prior to
screening will be excluded.