This study will assess the efficacy and safety of QVA149 compared to tiotropium plus formoterol in patients with moderate to severe COPD.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
934
QVA149 110/50µg, once daily (q.d.) is administered via a single-dose dry powder inhaler
Placebo to tiotropium capsules daily (q.d.) for inhalation, delivered via proprietary inhaler (Handihaler®). Placebo tiotropium inhalation capsules were matched in size and color to tiotropium 18 μg q.d. inhalation capsules
Placebo to formoterol capsules twice daily (b.i.d) delivered via Aerolizer® device. Placebo formoterol inhalation capsules were equally matched in size, shape and color to formoterol 12 μg b.i.d. inhalation capsules.
St. George's Respiratory Questionnaire (SGRQ-C) Total Score After 26 Weeks of Treatment (Non-inferiority Analysis).
SGRQ is a health related quality of life questionnaire consisting of 40 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status. For patients who completed the study but with missing SGRQ-C during treatment, the missing SGRQ-C were replaced by the last observation carried forward (LOCF). Symptom scores were expected to improve over treatment, therefore the replacement of missing values with earlier measurements did not result in overoptimistic imputation and this procedure could be regarded as conservative.
Time frame: Baseline, week 26
St. George's Respiratory Questionnaire (SGRQ-C) Total Score After 26 Weeks of Treatment (Superiority Analysis).
SGRQ is a health related quality of life questionnaire consisting of 40 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status. For patients who completed the study but with missing SGRQ-C during treatment, the missing SGRQ-C were replaced by the last observation carried forward (LOCF). Symptom scores were expected to improve over treatment, therefore the replacement of missing values with earlier measurements did not result in overoptimistic imputation and this procedure could be regarded as conservative. Superiority of QVA 110/50 μg to tiotropium 18 μg q.d. plus formoterol 12 μg b.i.d. in terms of health related quality of life as assessed by St George's Respiratory Questionnaire (SGRQ-C) after 26 weeks of treatment
Time frame: Baseline, week 26
Transition Dyspnea Index (TDI) Focal Score After 26 Weeks of Treatment.
Baseline Dyspnea Index (BDI)/Transition Dyspnea Index (TDI) focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. BDI was measured at day 1 prior to the first dose with domain scores ranging from 0=very severe to 4=no impairment and a total score ranging from 0 to 12(best). TDI captures changes from baseline. Each domain is scored from -3=major deterioration to 3=major improvement to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score. missing values were replaced by the latest observed value (LOCF)
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Tiotropium 18µg, once daily is administered via the manufacturer's proprietary inhalation device.
Formoterol 12µg, twice daily is administered via the manufacturer's proprietary inhalation device.
Placebo to QVA149 is administered via a single-dose dry powder inhaler. Placebo QVA149 inhalation capsules were equally matched in size, shape and color to QVA149 110/50 μg q.d. inhalation capsules
Novartis Investigative Site
Berlin, Germany, Germany
Novartis Investigative Site
Berlin, Germany, Germany
Novartis Investigative Site
Berlin, Germany, Germany
Novartis Investigative Site
Dresden, Germany, Germany
Novartis Investigative Site
Heidelberg, Germany, Germany
Novartis Investigative Site
Leipzig, Germany, Germany
Novartis Investigative Site
Mainz, Germany, Germany
Novartis Investigative Site
Marburg, Germany, Germany
Novartis Investigative Site
Potsdam, Germany, Germany
Novartis Investigative Site
Teterow, Germany, Germany
...and 134 more locations
Time frame: Week 26
Percent of Participants With at Least One Exacerbation Requiring Systemic Corticosteroids and/or Antibiotics Over 26 Weeks
The percent of participants with at least one moderate exacerbation within the 26 weeks that required systemic corticosteroids and/or antibiotics during the treatment
Time frame: Week 26
Percent of Participants With at Least One Exacerbation Requiring Hospitalization
The percent of patients with at least one severe exacerbation within the 26 weeks that required hospitalization. COPD exacerbations were considered to be severe if hospitalization were required.
Time frame: Week 26
Time- Event Analysis, Number of Participants With at Least One COPD Exacerbation (Moderate or Severe) During the Treatment Period
The number of participants with at least one moderate or severe COPD exacerbation. COPD exacerbations are considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required. COPD exacerbations are considered to be severe if hospitalizations were required.
Time frame: Week 26
Trough FEV1 at Baseline and Week 26
Trough FEV1 is the mean value of FEV1 (forced expiratory volume in one second) measured at 23:15h and 23:45h after the morning doses. The baseline value was measured at day 1 prior to the first dose.
Time frame: Baseline, Week 26
FEV1 30 Min After the Morning Dose at Baseline and Week 26
FEV1 30min is the forced expiratory volume in one second measured 30 min after the morning dose.
Time frame: Baseline, Week 26
Symptoms Score Reported by the Patients Using Part I "Symptoms" of SGRO-C
Part I of the SGRQ-C covers "symptoms" and is concerned with respiratory symptoms, their frequency and severity. Each questionnaire response has a unique empirically derived "weight". A score was calculated from these weights. The lowest possible value is zero and the highest 100. A higher value corresponds to greater impairment of health status.
Time frame: Baseline, Week 26