- Informed consent: Subjects must give their signed and dated written informed consent
- Gender: Male or female subjects. Female subjects must be post-menopausal or using a
highly effective method for avoidance of pregnancy. The decision to include or exclude
women of childbearing potential may be made at the discretion of the investigator in
accordance with local practice in relation to adequate contraception.
- Age: >= 40 years of age at Screening (Visit 1)
- COPD diagnosis: Subjects with a clinical history of COPD in accordance with the
following definition by the American Thoracic Society/European Respiratory Society:
COPD is a preventable and treatable disease 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.
- Tobacco use: Subjects with a current or prior history of >=10 pack-years of cigarette
smoking at screening (Visit 1). 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 Note: Pipe and/or cigar use cannot be
used to calculate pack year history.
- Severity of Disease: Subject with a measured post-albuterol/salbutamol Forced
expiratory volume (FEV1)/forced vital capacity (FVC) ratio of <0.70 at Screening
(Visit 1). Subjects with a measured post-albuterol/salbutamol 50% <=FEV1 <=70% of
predicted normal values calculated using National Health and Nutrition Examination
Survey (NHANES III) reference equations at Screening (Visit 1).
- Native Hip: Have at least one evaluable native hip.
- Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant
during the study.
- 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).
- Alpha1-antitrypsin deficiency: Subjects with alpha-1 antitrypsin deficiency as the
underlying cause of COPD.
- Other respiratory disorders: Subjects with tuberculosis, lung cancer, bronchiectasis,
sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases or
other active pulmonary diseases.
- Lung resection or transplantation: Subjects with lung volume reduction surgery within
the 12 months prior to Screening Visit 1 or having had a lung transplant.
- Chest X-ray: Subjects with a chest X-ray (or Computer Axial Tomography (CT) scan) that
revealed evidence of clinically significant abnormalities not believed to be due to
the presence of COPD. A chest X-ray should be taken at Screening Visit 1 if a chest
X-ray or CT scan is not available within 12 months prior to Visit 1.
- Poorly controlled COPD: Subjects with poorly controlled COPD, defined as the
occurrence of the following in the 12 weeks prior to Screening Visit 1: Acute
worsening of COPD that is managed by the subject with corticosteroids or antibiotics
or that requires treatment prescribed by a physician or requires hospitalization.
- Moderate or severe COPD exacerbation or lower respiratory tract infection: Subjects
with 2 or more moderate or severe COPD exacerbations and/or a lower respiratory tract
infection (including pneumonia) within the 12 months prior to Screening Visit 1 or
experience a moderate or severe COPD exacerbation and/or a lower respiratory infection
(including pneumonia) during the Run-In period. NOTE: A moderate COPD exacerbation is
defined as requiring systemic corticosteroids and/or antibiotics. A severe COPD
exacerbation is defined as requiring hospitalization.
- Abnormal clinically significant laboratory finding: Subjects who have an abnormal,
clinically significant finding in any liver chemistry, biochemical, or haematology
tests at Screening Visit 1 or upon repeat prior to randomization.
- Abnormal and clinically significant 12-lead Electrocardiogram (ECG): Subjects who have
an abnormal, clinically significant ECG finding at Screening Visit 1.
- Non-Compliance during Run-In Period: Failure to demonstrate adequate compliance with
run-in medication (< 80% compliant), the ability to withhold COPD medications, and to
keep clinic visit appointments.
- Bone disorders/conditions: Subjects with historical or current evidence of bone
cancer, severe scoliosis, rheumatoid arthritis, metabolic bone diseases (other than
osteoporosis) including hyper-or hypo-parathyroidism, Paget's disease of bone,
osteomalacia, or osteogenesis imperfecta. Removal of vertebrae between L1 and L4 of
the lumbar spine and/or presence of metal implants or devices, such as plates, rods,
or screws in the lumbar spine and/or hip.
- Immobility: Wheel chair bound or paraplegic.
- Low vitamin D: Previously known low-serum 25-hydroxy vitamin D concentration (less
than 10ng [25nmoles] per liter).
- Other diseases/abnormalities: Serious, uncontrolled disease (including serious
psychological disorders) likely to interfere with the study within the 3-year study.
- Cancer: Subjects with carcinoma that has not been in complete remission for at least 5
years. Carcinoma in situ of the cervix, squamous cell carcinoma and basal cell
carcinoma of the skin would not be excluded if the subject has been considered cured
within 5 years since diagnosis.
- Drug/food allergy: Subjects with a history of hypersensitivity to any of the study
medications (e.g. beta-agonists, corticosteroid) or components of the inhalation
powder (e.g. lactose, magnesium stearate). In addition, patients with a history of
severe milk protein allergy that, in the opinion of the study physician,
contraindicates the subject's participation will also be excluded.
- Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug
abuse within the last 2 years.
- Prohibited medications prior to spirometry at Visit 1: Subjects who are medically
unable to withhold the following medications prior to spirometry testing at Visit 1
- No use within 48 hours (hrs) prior to Visit 1 Spirometry Testing: Inhaled
corticosteroids, Inhaled Inhaled Corticosteroids (ICS)/ long acting beta2-agonist
(LABA) combination products, Long-acting anticholinergics (e.g., tiotropium),
Theophylline preparations, Oral leukotriene inhibitors (zafirlukast, montelukast,
zileuton), Oral PDE-4 inhibitors (e.g. roflumilast), Oral beta-agonists (Long-acting),
Inhaled long acting beta2-agonist (LABA)-Indacaterol.
- No use within 24 hrs prior to Visit 1 Spirometry Testing: Other inhaled LABAs (e.g.,
salmeterol), Inhaled sodium cromoglycate or nedocromil sodium.
- No use within 12 hrs prior to Visit 1 Spirometry Testing: Oral beta-agonists
- No use within 4 hrs prior to Visit 1 Spirometry Testing: Ipratropium/ albuterol
(salbutamol) combination product, Inhaled short-acting beta2-agonists, Short-acting
anti-cholinergics (e.g., ipratropium bromide).
- Additional medication: Use of the following medications within the following time
intervals prior to Visit 1 or during the study (unless otherwise specified):
- No use within 12 weeks prior to Screening Visit 1 or thereafter at any time during the
study (unless otherwise specified): Depot corticosteroids.
- No use within 30 days prior to Screening Visit 1 or thereafter at any time during the
study (unless otherwise specified): Systemic, Oral, parenteral, intra-articular
corticosteroids (Subjects may take courses of systemic corticosteroids, where
necessary, for treatment of an exacerbation during the double-blind treatment period).
- No use within 30 days or 5 half lives whichever is longer prior to Screening Visit 1
or thereafter at any time during the study (unless otherwise specified): Any other
- COPD medications: Use of ICS, long-acting beta2-agonists (LABA), or ICS/LABA
combination products (other than the study-provided double-blind study medication) at
Visit 2 (Randomization) or during the double-blind treatment period.
- Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy (LTOT) or
nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen prn use
(i.e., <=12 hours per day) is not exclusionary.
- 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: Study investigators, sub-investigators, study
coordinators, employees of a participating investigator or immediate family members of
the aforementioned are excluded from participating in this study.