Comparison of Long-term Safety of the Combination Product QVA149A Against Placebo and Standard of Care Treatment in Chronic Obstructive Pulmonary Disease Patients With Moderate to Severe Airflow Limitation
- Conditions
- Chronic Obstructive Pulmonary Disease (COPD)
- Interventions
- Registration Number
- NCT01610037
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
The study will assess the long-term safety of the fixed combination product QVA149 versus placebo and a standard of care treatment (tiotropium) in Chronic Obstructive Pulmonary Disease (COPD) patients with moderate to severe airflow limitation.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1215
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description QVA149 QVA149 - placebo placebo - Tiotropium Tiotropium -
- Primary Outcome Measures
Name Time Method Number of Patients With Serious Adverse Events Week 52 The overall rate of serious adverse events reported from initiation through 30 days post last dose.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Percentage of no Daytime Symptoms 52 weeks A day with 'no daytime symptoms' is defined from the diary data as any day where the patient has recorded in the evening no cough, no wheeze, no production of sputum and no feeling of breathlessness (other than when running) during the past 12 hours (approx. 8 am to 8 pm).
Change From Baseline in Pre-Dose Forced Expiratory Volume Over in Second (FEV1) Day 22, 43, 85, 183, 274 and 364 Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1.
Change From Baseline in 1 Hour Post-dose FEV1 Measurements Day 1, 22, 43, 85, 183, 274 and 364 The avg 60 min post dose forced expiratory volume in 1 second (FEV1) at visit 4, 5, 6, 7, 8 and 9 will be analyzed.
Post-hoc Analysis: Percentage of Patients With Composite Endpoint of Cardiovascular Death and MACE 52 weeks The composite endpoint included all deaths and all serious CCV events, including MACE and events which were not considered MACE. A rigorous post hoc analysis was done on composite endpoint of CV deaths and major adverse cardiovascular events (MACE). The patients with an event in the analysis were those who had at least one of the 2 events namely, CV deaths and MACE, during treatment or within 30 days after the date of last dose of study drug.
Change From Baseline in Daily, Morning and Evening Symptom Scores 52 weeks Patients will be provided with an electronic diary (eDiary) to record daily clinical symptoms, or rescue medication. The patients will be instructed to routinely complete the patient diary twice daily. There are 9 total symptom questions for a total possible score of 27 at each timepoint. A higher score means the patient is reporting more symptoms related to Chronic Obstructive Pulmonary Disease. The mean daily total symptom score, the mean daytime total symptom score and the mean nighttime total symptom score were calculated for each patient over 52 weeks. Diary data recorded during the 14 day run-in period were used to calculate the baseline.
Percentage of Patients With Composite Endpoint of All-cause Mortality, and Serious Cardio- and Cerebrovascular (CCV) Events. 52 weeks The endpoint of all-cause mortality and serious CCV events (composite) was chosen to further characterize any discernible risks. The patients with an event in the analysis were those who had at least one of the 2 events namely, all-cause mortality and serious CCV, during treatment or within 30 days after the date of last dose of study drug.
Change From Baseline in Health Status as Measured by St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Measurment at day 364 The SGRQ-C contains 40 items divided into two parts covering three aspects of health related to COPD: Part I covers "Symptoms" and is concerned with respiratory symptoms, their frequency and severity; Part II covers "Activity" and is concerned with activities that cause or are limited by breathlessness; Part II is also concerned with "Impacts" which covers a range of aspects concerned with social functioning and psychological disturbances resulting from airways disease. A score will be calculated for each of these three subscales and a "Total" score will also be calculated. In each case the lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status.
Change From Baseline in Percentage of Nights With 'no Nighttime Awakenings 52 weeks A night with 'no nighttime awakenings' is defined from diary data as any night where the patient did not wake up due to symptoms.
Change From Baseline in Percentage of Days Able to Perform Usual Daily Activities. 52 weeks A day able to perform usual daily activities' is defined from diary data as any day where the patient was not prevented from performing their usual daily activities due to respiratory symptoms.
Change From Baseline in 1 Hour Post-dose Forced Vital Capacity (FVC) Measurements Day 1, 22, 43, 85, 183, 274 and 364 Pulmonary function assessments were performed using centralized spirometry according to international standards
Time to Premature Discontinuation Time varied from 5 - 407 days Time to premature treatment discontinuation for each treatment group was displayed using a Kaplan-Meier curve. The date of last dose of study medication was considered as the event date and also as the censoring date for those patients who did not discontinue treatment early. The range of the 'time to treatment discontinuation' varied from 5-407 days in the Tiotropium group. Hence the model estimated lower limit of the median time to treatment discontinuation is greater than the scheduled treatment period of 52 weeks.
Trial Locations
- Locations (1)
Novartis Investigative Site
🇬🇧Wolverhampton, United Kingdom