This is a Phase IIIb multicentre, randomised, blinded, triple dummy, parallel group study to
evaluate the efficacy and safety of UMEC/VI inhalation powder (62. 5/25 microgram [mcg] Once
daily [QD]) when administered via ELLIPTA® Dry Powder Inhaler (DPI) compared to indacaterol
plus tiotropium (150 mcg/18 mcg respectively QD) administered via individual inhalers over a
treatment period of 12 weeks in participants with moderate to very severe Chronic
Obstructive Pulmonary Disease (COPD). The purpose of this study is to demonstrate that
UMEC/VI (delivered via ELLIPTA DPI), when used in symptomatic moderate to very severe COPD
participants, is non-inferior to the combination of indacaterol (delivered via BREEZHALER®
inhaler) plus tiotropium (delivered via HANDIHALER® inhaler) on measures of trough forced
expiratory volume in one second (FEV1) after 12 weeks of treatment. Participants who met the
eligibility criteria at screening (Visit 1) will complete a 5 to 7 day run in period prior
to randomisation at Visit 2. Clinic visits will follow at day 2, week 2, week 4, week 8 and
week 12 of treatment, plus week 12 + 1 day (Visits 3 to 8). The total duration of study
participation will be approximately 14 weeks. ELLIPTA is a registered trademark of the GSK
group of companies. HANDIHALER is a registered trademark of Boehringer Ingelheim Pharma GmbH
& Co. KG. BREEZHALER is a registered trademark of Novartis AG.
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.
- Participants 40 years of age or older at Visit 1.
- Gender: Male or female participants. 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 Standard Operating Procedure (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. Former smokers are defined as those who have stopped
smoking for at least 6 months prior to Visit 1.
- 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 pre and
post-albuterol/salbutamol FEV1 of <=70% predicted normal value at Visit 1, calculated
using Quanjer reference equations.
- Dyspnoea: A score of >= 2 on the Modified Medical Research Council Dyspnoea Scale
(mMRC) at Visit 1.
- QT interval corrected (QTc) Criteria: QTc <450 milliseconds (msec) or QTc <480 msec
for patients with bundle branch block 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 Electrocardiogram
(ECGs) obtained over a brief recording period.
- French participants: In France, a subject will be eligible for inclusion in this
study only if either affiliated to or a beneficiary of a social security category.
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. Allergy rhinitis is not exclusionary.
- Other Diseases/Abnormalities: Participants 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, 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 or beta 2
agonist.
- Hospitalisation: Hospitalisation for COPD or pneumonia within 12 weeks prior to Visit
1.
- Lung Resection: Participants with lung volume reduction surgery within the 12 months
prior to Screening (Visit 1).
- 12-Lead ECG: An abnormal and significant ECG finding from the 12-lead ECG conducted
at Visit 1. Specific ECG findings that preclude subject eligibility will be listed in
protocol The study investigator will determine the medical significance of any ECG
abnormalities not listed.
- Screening labs: Significantly abnormal finding from clinical chemistry or haematology
tests at Visit 1 as determined by the study investigator.
- 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);
Oral or parenteral corticosteroids (6 weeks); Antibiotics (for lower respiratory
tract infection) (6 weeks); Cytochrome P450 3A4 strong inhibitors ( 6 weeks); Long
Acting Beta-Agonist (LABA)/ inhaled corticosteroids (ICS) combination products (e. g.
fluticasone/salmeterol, mometasone, furoate/formoterol fumarate,
budesonide/formoterol, fumarate), If LABA/ICS therapy is discontinued completely (30
days); If discontinuing LABA therapy and switching to ICS monotherapy (48 hours for
salmeterol or formoterol, 14 days for Olodaterol, Indacaterol or, Vilanterol); Use of
ICS at a dose >1000 mcg/day of fluticasone propionate or equivalent (30 days);
Initiation or discontinuation of ICS use (30 days); Inhaled long acting
beta2-agonists (LABA): Salmeterol, Formoterol (48 hours), Olodaterol, Indacaterol and
Vilanterol (14 days); Long acting muscarinic antagonists (LAMA) (Tiotropium,
Aclidinium, Glycopyrronium, Umeclidinium) (7 days); LABA/LAMA combination products
(Whichever mono component has the longest washout); Roflumilast (14 days); Oral
beta-agonists- Long-acting (48 hours), Short-acting(12 hours); Theophyllines (48
hours); Oral leukotriene inhibitors (zafirlukast, montelukast, zileuton) (48 hours);
Inhaled sodium cromoglycate or nedocromil sodium (24 hours); Inhaled short acting
beta2-agonists (4 hours); Inhaled short-acting anticholinergic (short acting
muscarinic antagonist [SAMA]) products eg ipratropium (4 hours); Inhaled short-acting
anticholinergic/short-acting beta2-agonist combination products (SAMA/Short Acting
beta2-agonists [SABA]) (4 hours); Any other investigational medication (30 days or
within 5 drug half-lives)
- Oxygen: Use of Long Term Oxygen Therapy (LTOT).This is defined as oxygen therapy
prescribed for greater than 12 hours per 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 12 weeks prior to Visit 1. Participants 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.
- Participants who are pre-screen or screen failures cannot be re-screened.
GSK Investigational Site, Buenos Aires C1424BSF, Argentina
GSK Investigational Site, Buenos Aires C1425BEN, Argentina
GSK Investigational Site, Ciudad Autónoma de Buenos Aires C1426ABP, Argentina
GSK Investigational Site, Mendoza 5500, Argentina
GSK Investigational Site, Mendoza M5500CCG, Argentina
GSK Investigational Site, San Miguel de Tucumán 4000, Argentina
GSK Investigational Site, Santiago 7500698, Chile
GSK Investigational Site, Haapsalu 90502, Estonia
GSK Investigational Site, Tallinn 10117, Estonia
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GSK Investigational Site, Gières 38610, France
GSK Investigational Site, Nantes cedex 2 44277, France
GSK Investigational Site, Perpignan 66000, France
GSK Investigational Site, Reims Cedex 51092, France
GSK Investigational Site, Strasbourg cedex 67091, France
GSK Investigational Site, Tarbes Cedex 09 65013, France
GSK Investigational Site, Berlin 10367, Germany
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GSK Investigational Site, Pécs 7635, Hungary
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GSK Investigational Site, Frankfurt am Main, Hessen 60596, Germany
GSK Investigational Site, Frankfurt, Hessen 60389, Germany
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