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
|ClinicalTrials.gov Identifier: NCT01610037|
Recruitment Status : Completed
First Posted : June 1, 2012
Results First Posted : June 15, 2016
Last Update Posted : June 15, 2016
|Condition or disease||Intervention/treatment||Phase|
|Chronic Obstructive Pulmonary Disease (COPD)||Drug: QVA149 Drug: Tiotropium Drug: placebo||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1215 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||A Placebo and Active Controlled Study to Assess the Long-term Safety of Once Daily QVA149 for 52 Weeks in Chronic Obstructive Pulmonary Disease (COPD) Patients With Moderate to Severe Airflow Limitation|
|Study Start Date :||October 2012|
|Primary Completion Date :||February 2015|
|Study Completion Date :||February 2015|
QVA149 110/50 µg will be supplied as capsules in blister packs for once daily inhalation using the Novartis Concept1 SDDPI
|Active Comparator: Tiotropium||
Tiotropium 18 µg will be supplied as capsules in blister packs for once daily inhalation using the HandiHaler SDDPI
|Placebo Comparator: placebo||
placebo to QVA149A and Tiotropium will be supplied in the appropriate capsule in blister packs for use in either the Novartis Concept1 SDDPI or the HandiHaler SDDPI
- Number of Patients With Serious Adverse Events [ Time Frame: Week 52 ]The overall rate of serious adverse events reported from initiation through 30 days post last dose.
- Percentage of Patients With Composite Endpoint of All-cause Mortality, and Serious Cardio- and Cerebrovascular (CCV) Events. [ Time Frame: 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.
- Post-hoc Analysis: Percentage of Patients With Composite Endpoint of Cardiovascular Death and MACE [ Time Frame: 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 Pre-Dose Forced Expiratory Volume Over in Second (FEV1) [ Time Frame: 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 Health Status as Measured by St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C) [ Time Frame: 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 Daily, Morning and Evening Symptom Scores [ Time Frame: 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.
- Change From Baseline in Percentage of Nights With 'no Nighttime Awakenings [ Time Frame: 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 no Daytime Symptoms [ Time Frame: 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 Percentage of Days Able to Perform Usual Daily Activities. [ Time Frame: 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 [ Time Frame: 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 Frame: 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.
- Change From Baseline in 1 Hour Post-dose FEV1 Measurements [ Time Frame: 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01610037
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|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|