This is a multicenter, randomized, double-blind, double-dummy, parallel group study. The
purpose of this study is to compare the efficacy and safety of umeclidinium/vilanterol
(UMEC/VI) and fluticasone propionate/salmeterol (FSC) in subjects with Chronic Obstructive
Pulmonary Disease (COPD). Subjects who meet the eligibility criteria at Screening will
complete a 7 to 14 day Run-in period. At the end of the run-in period, approximately 710
eligible subjects will be equally randomized (to complete at least 568 evaluable subjects)
to one of the 2 treatment groups for 12 weeks: 1. UMEC/VI 62. 5/25 micrograms (mcg)
administered as one inhalation once-daily in the morning via the Novel dry powder inhaler
(NDPI) + placebo administered as one inhalation each morning and evening via single
multidose powdered inhaler (ACCUHALER/DISKUS) or 2. FSC 500/50 mcg administered as one
inhalation each morning and evening via ACCUHALER/DISKUS + placebo administered once-daily
in the morning via NDPI. A safety Follow-up assessment will be conducted approximately 7
days after the end of the study treatment (Early Withdrawal, if applicable). The total
duration of subject participation will be approximately 15 weeks.
Minimum age: 40 Years.
Maximum age: N/A.
Gender(s): Both.
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); or Child bearing potential, has a negative pregnancy test at screening, and
agrees to one of the acceptable contraceptive methods listed in the protocol used
consistently and correctly
- Diagnosis: 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. Although COPD affects the lungs, it also produces significant systemic
consequences.
- 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)]. Previous smokers are defined as those who have stopped
smoking for at least 6 months prior to Visit 1. Pipe and/or cigar smoking cannot be
used to calculate pack year history.
- Severity of disease: A pre and post-salbutamol FEV1/FVC ratio of <0. 70 and a
post-salbutamol FEV1 of >=30% and <=70% of predicted normal values calculated using
NHANES III reference equations at Visit 1.
- 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 condition in addition to COPD should be excluded. Examples
may include clinically significant bronchiectasis, pulmonary hypertension,
sarcoidosis, or interstitial lung disease. Inactive tuberculosis in more than one
lobe is exclusionary. Allergic rhinitis is not exclusionary.
- 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: A history of allergy or hypersensitivity to any
anticholinergic/muscarinic receptor antagonist, beta2-agonist, corticosteroid,
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 anticholinergic.
- Hospitalization: Hospitalization for pneumonia within 12 weeks prior to Visit 1
- History of COPD Exacerbation: A documented history of at least one COPD exacerbation
in the 12 months prior to Visit 1 that required either oral corticosteroids,
antibiotics, and/or hospitalization. Prior use of antibiotics alone does not qualify
as an exacerbation history unless the use was associated with treatment of worsening
symptoms of COPD, such as increased dyspnea, sputum volume, or sputum purulence.
- Lung Resection: Subjects with lung volume reduction surgery within the 12 months
prior to Screening (Visit 1)
- 12-Lead ECG: An abnormal and significant electrocardiogram (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.
- Medication Prior to Spirometry: Unable to withhold 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, Cytochrome P450 3A4 strong inhibitors - 6
weeks, Herbal medications potentially containing oral or systemic steroids - 6 weeks,
Inhaled corticosteroids (ICS) - 30 days, Long-acting beta2-agonist (LABA)/ICS
combination products - 30 days, Phosphodiesterase 4 (PDE4) inhibitors (e. g.,
roflumilast) - 14 days, Inhaled long-acting anticholinergics - 7 days, Theophyllines
- 48 hours, Oral leukotriene inhibitors (zafirlukast, montelukast, zileuton) - 48
hours, Oral beta2-agonists Long-acting-48 hours/Short-acting - 12 hours, Inhaled long
acting beta2-agonists (LABA, e. g., salmeterol, formoterol, indacaterol) - 48 hours,
Inhaled sodium cromoglycate or nedocromil sodium - 24 hours, Inhaled short acting
beta2-agonists - 4 hours, 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., 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: 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: A subject will not be eligible for the study if in the opinion of
the investigator the subject cannot read.
GSK Investigational Site, Benesov 256 30, Czech Republic
GSK Investigational Site, Cvikov 471 54, Czech Republic
GSK Investigational Site, Kralupy nad Vltavou 278 01, Czech Republic
GSK Investigational Site, Kromeriz 767 55, Czech Republic
GSK Investigational Site, Praha 5 150 00, Czech Republic
GSK Investigational Site, Rokycany 337 01, Czech Republic
GSK Investigational Site, Teplice 415 10, Czech Republic
GSK Investigational Site, Trebic 674 01, Czech Republic
GSK Investigational Site, Hvidovre 2650, Denmark
GSK Investigational Site, København 2400, Denmark
GSK Investigational Site, Odense C 5000, Denmark
GSK Investigational Site, Roskilde 4000, Denmark
GSK Investigational Site, Berlin 10117, Germany
GSK Investigational Site, Berlin 10629, Germany
GSK Investigational Site, Berlin 10717, Germany
GSK Investigational Site, Berlin 10787, Germany
GSK Investigational Site, Berlin 10789, Germany
GSK Investigational Site, Berlin 13125, Germany
GSK Investigational Site, Balassagyarmat 2660, Hungary
GSK Investigational Site, Budaörs 2040, Hungary
GSK Investigational Site, Debrecen 4032, Hungary
GSK Investigational Site, Debrecen 4043, Hungary
GSK Investigational Site, Farkasgyepű 8552, Hungary
GSK Investigational Site, Gödöllő 2100, Hungary
GSK Investigational Site, Miskolc 3529, Hungary
GSK Investigational Site, Mosonmagyaróvár 9200, Hungary
GSK Investigational Site, Nyíregyháza 4400, Hungary
GSK Investigational Site, Pecs H-7621, Hungary
GSK Investigational Site, Szeged 6722, Hungary
GSK Investigational Site, Szikszó 3800, Hungary
GSK Investigational Site, Székesfehérvár 8000, Hungary
GSK Investigational Site, Dordrecht 3318 AT, Netherlands
GSK Investigational Site, Eindhoven 5623 EJ, Netherlands
GSK Investigational Site, Heerlen 6419 PC, Netherlands
GSK Investigational Site, Hoorn 1624 NP, Netherlands
GSK Investigational Site, Kloosterhaar 7694 AC, Netherlands
GSK Investigational Site, Sneek 8601 ZR, Netherlands
GSK Investigational Site, Gdansk 80-169, Poland
GSK Investigational Site, Inowroclaw 88-100, Poland
GSK Investigational Site, Krakow 31-024, Poland
GSK Investigational Site, Poznan 60-773, Poland
GSK Investigational Site, Skierniewice 96-100, Poland
GSK Investigational Site, Slupsk 76-200, Poland
GSK Investigational Site, Barnaul 656038, Russian Federation
GSK Investigational Site, Blagoveshchensk 675000, Russian Federation
GSK Investigational Site, Kaluga 248007, Russian Federation
GSK Investigational Site, Kazan 420015, Russian Federation
GSK Investigational Site, Khantymansiysk 628012, Russian Federation
GSK Investigational Site, Moscow 123367, Russian Federation
GSK Investigational Site, Moscow 105 077, Russian Federation
GSK Investigational Site, Moscow 121 309, Russian Federation
GSK Investigational Site, Moscow 123182, Russian Federation
GSK Investigational Site, Moscow 115446, Russian Federation
GSK Investigational Site, Nizhniy Novgorod 603126, Russian Federation
GSK Investigational Site, Orenburg 460018, Russian Federation
GSK Investigational Site, Petrozavodsk 185019, Russian Federation
GSK Investigational Site, Ryazan 390039, Russian Federation
GSK Investigational Site, Saratov 410028, Russian Federation
GSK Investigational Site, St Pertersburg 196247, Russian Federation
GSK Investigational Site, St. Petersburg 194356, Russian Federation
GSK Investigational Site, Tomsk 634 050, Russian Federation
GSK Investigational Site, Ufa 450000, Russian Federation
GSK Investigational Site, Alicante 03004, Spain
GSK Investigational Site, L'Hospitalet de Llobregat 08907, Spain
GSK Investigational Site, Madrid 28041, Spain
GSK Investigational Site, Pama de Mallorca 07010, Spain
GSK Investigational Site, Ponferrada (León) 24411, Spain
GSK Investigational Site, Valladolid 47012, Spain
GSK Investigational Site, Dillingen, Bayern 89407, Germany
GSK Investigational Site, Ruedersdorf, Brandenburg 15562, Germany
GSK Investigational Site, Barcelona, Catalonia 08017, Spain
GSK Investigational Site, Frankfurt am Main, Hessen 60596, Germany
GSK Investigational Site, Frankfurt, Hessen 60389, Germany
GSK Investigational Site, Frankfurt, Hessen 60596, Germany
GSK Investigational Site, Neu isenburg, Hessen 63263, Germany
GSK Investigational Site, Schwerin, Mecklenburg-Vorpommern 19055, Germany
GSK Investigational Site, Delitzsch, Sachsen 04509, Germany
GSK Investigational Site, Dresden, Sachsen 01069, Germany
GSK Investigational Site, Magdeburg, Sachsen-Anhalt 39112, Germany