A 64-week Treatment, Multi-center, Randomized, Double-blind, Parallel-group, Active Controlled Study to Evaluate the Effect of QVA149 (110/50 ÎĽg o.d.) vs NVA237 (50 ÎĽg o.d.) and Open-label Tiotropium (18 ÎĽg o.d.) on COPD Exacerbations in Patients With Severe to Very Severe Chronic Obstructive Pulmonary Disease (COPD)
A 64-week Treatment, Multi-center, Randomized, Double-blind, Parallel-group, Active Controlled Study to Evaluate the Effect of QVA149 (110/50 ÎĽg o.d.) vs NVA237 (50 ÎĽg o.d.) and Open-label Tiotropium (18 ÎĽg o.d.) on COPD Exacerbations in Patients With Severe to Very Severe Chronic Obstructive Pulmonary Disease (COPD)
This study is designed to assess the effect of once-daily QVA149 on COPD exacerbations in patients with severe to very severe COPD.
Inclusion Criteria :
Exclusion Criteria:
Pregnant women or nursing mothers (pregnancy confirmed by positive urine pregnancy test).
Women of child-bearing potential
Patients requiring long term oxygen therapy (> 15 h a day) on a daily basis for chronic hypoxemia.
Patients who had a COPD exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization in the 6 weeks prior to visit 1 or between visit 1 (Day -21) and Visit 3 (Day 1).
Patients who developed a COPD exacerbation during a period between visit 1 and 3 were ineligible but were permitted to be re-screened after a minimum of 6 weeks after the resolution of the COPD exacerbation.
Patients who had a respiratory tract infection within 4 weeks prior to visit 1 (Day -21)
• Patients who developed an upper or lower respiratory tract infection during the screening period (up to visit 3 (Day 1) were not eligible, but were permitted to be re-screened 4 weeks after the resolution of the respiratory tract infection
Patients with concomitant pulmonary disease, e.g. pulmonary tuberculosis (unless confirmed by chest x-ray to be no longer active), clinically significant bronchiectasis, sarcoidosis, interstitial lung disorder or pulmonary hypertension.
Patients with lung lobectomy, or lung volume reduction or lung transplantation.
Patients who, in the judgment of the investigator, have a clinically relevant laboratory abnormality or a clinically significant condition such as (but not limited to):
Patients with any history of asthma indicated by (but not limited to) a blood eosinophil count > 600/mm3 (at visit 2), or onset of symptoms prior to 40 years. Patients without asthma were excluded if their eosinophil count was >600/mm3 at visit 2.
Patients with allergic rhinitis who used H1 antagonists or intranasal corticosteroids intermittently (treatment with a constant dose was permitted).
Patients with eczema (atopic), known high immunoglobulin E (IgE) levels or a known positive skin prick test in the last 5 years.
Patients with known history and diagnosis of alpha-1 antitrypsin deficiency.
Patients who were participating in the active phase of a supervised pulmonary rehabilitation program.
Patients with Type I or uncontrolled Type II diabetes.
Patients contraindicated for treatment with, or having a history of reactions/ hypersensitivity to any of the following inhaled drugs or drugs of a similar class or any component thereof:
Patients with a history of long QT syndrome or whose corrected QT interval (QTc) measured at visit 2 (Day -14) (Fridericia method) was prolonged (>450 ms for males and females) as confirmed by the central ECG assessor.
Patients with a clinically significant abnormality on the screening or baseline ECG who in the judgment of the investigator would be at potential risk if enrolled into the study. (These patients could not be re-screened).
Patients who needed treatments for COPD and allied conditions after the start of the study (visit 1)
Patients who needed treatments for COPD and allied conditions (e.g. allergic rhinitis) unless they had been stabilized
Patients taking other prohibited medications
Patients unable to use a dry powder inhaler (e.g. single dose dry powder inhaler (SDDPI), HandiHaler® device, or pressurized Metered Dose Inhaler (MDI) (rescue medication).
Patients unable to use an electronic patient diary.
Patients who were, in the opinion of the investigator known to be unreliable or non-compliant.
Patients who used other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of visit 1 (day -21), whichever was longer.
Patients who had live attenuated vaccination within 30 days prior to the screening visit or during the run-in period. Inactivated influenza vaccination, pneumococcal vaccination or any other inactivated vaccine was acceptable provided it was not administered within 48 hours prior to screening and randomization visits.
No additional exclusions were applied by the investigator, in order to ensure that the study population was representative of all eligible patients.
Couer D'Alene, Idaho 83814, United States
Paraná Entre RĂos, Argentina 3100, Argentina
Buenos Aires, Buenos Aires B1842DID, Argentina
Buenos Aires, Buenos Aires B1878FNR, Argentina
Buenos Aires, Buenos Aires B2705XAE, Argentina
Buenos Aires, Buenos Aires B8000XAV, Argentina
Buenos Aires, Buenos Aires C1013AAR, Argentina
Buenos Aires, Buenos Aires C1115AAB, Argentina
Buenos Aires, Buenos Aires C1120AAC, Argentina
Buenos Aires, Buenos Aires C1122AAK, Argentina
Buenos Aires, Buenos Aires C1125ABE, Argentina
Buenos Aires, Buenos Aires C1405BCH, Argentina
Buenos Aires, Buenos Aires C1425AUA, Argentina
Buenos Aires, Buenos Aires C1425BEA, Argentina
Buenos Aires, Buenos Aires, Argentina
Capital Federal, Buenos Aires C1424BSF, Argentina
Bogota, Cundinamarca, Colombia
Copenhagen NV, DK-2400, Denmark
Ferolles-Attily, France 77150, France
Koblenz, North Rhine-Westphalia 56068, Germany
Athens - GR, 10676, Greece
Hyderbabd, Andhra Pradesh 500 029, India
Nagpur - Maharastra, India 400 012, India
S.-Petersburg, 196247, Russia
Newtown, Johannesburg, 2193, South Africa
Merseyside, CH49 5PE, United Kingdom