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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01610037
First received: May 30, 2012
Last updated: May 9, 2016
Last verified: May 2016

May 30, 2012
May 9, 2016
October 2012
February 2015   (final data collection date for primary outcome measure)
Number of Patients With Serious Adverse Events [ Time Frame: Week 52 ] [ Designated as safety issue: Yes ]
The overall rate of serious adverse events reported from initiation through 30 days post last dose.
overall serious adverse event rate [ Time Frame: 56 weeks ] [ Designated as safety issue: Yes ]
The overall rate of serious adverse events reported from initiation through 30 days post last dose will be analyzed.
Complete list of historical versions of study NCT01610037 on ClinicalTrials.gov Archive Site
  • Percentage of Patients With Composite Endpoint of All-cause Mortality, and Serious Cardio- and Cerebrovascular (CCV) Events. [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Pulmonary function assessments were performed using centralized spirometry according to international standards
  • Time to Premature Discontinuation [ Time Frame: Time varied from 5 - 407 days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.
  • Electrocardiogram [ Time Frame: weeks 1, 26 and 52 ] [ Designated as safety issue: No ]
    Data from the electrocardiograms will be summarized by treatment at all times.
  • Health Status as measured by Saint George's Respiratory Questionnaire (SGRQ-C) for Chronic Obstructive Pulmonary Disease (COPD) patients [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    The Saint George's Respiratory Questionnaire (SGRQ-C) will be used to provide the health status measurement. The SGRQ-C contains 40 items divided into two parts covering three aspects of health related to Chronic Obstructive Pulmonary Disease. A score will be calculated for each of these three parts 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
  • Impairment of health status daily, morning and evening symptom scores [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    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.
  • Percentage of nights with 'no nighttime awakenings' [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    A night with 'no nighttime awakenings' is defined from diary data as any night where the patient did not wake up due to symptoms. The percentage of nights with 'no nighttime awakenings' will be analyzed.
  • Percentage of days with 'no daytime symptoms' [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    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). The percentage of days with 'no daytime symptoms' will be analyzed.
  • Percentage of 'days able to perform usual daily activities' [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    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. The percentage of 'days able to perform usual daily activities' will be analyzed.
  • Pre-dose Forced Expiratory Volume in one second (FEV1) [ Time Frame: Weeks 3, 6, 12, 26, 39, and 52 ] [ Designated as safety issue: No ]
    The average pre-dose forced expiratory volume in 1 second (FEV1) at visit 4, 5, 6, 7, 8 and 9 will be analyzed.
  • Pre-Dose forced vital capacity (FVC) [ Time Frame: Weeks 3, 6, 12, 26, 39 and 52 ] [ Designated as safety issue: No ]
    The average pre-dose forced vital capacity (FVC) at visit 4, 5, 6, 7, 8 and 9 will be analyzed.
  • Post dose forced expiratory volume in one second (FEV1) [ Time Frame: Weeks 3, 6, 12, 26, 39, and 52 ] [ Designated as safety issue: No ]
    The average 60 minute post dose forced expiratory volume in 1 second (FEV1) at visit 4, 5, 6, 7, 8 and 9 will be analyzed
  • Post Dose forced vital capacity (FVC) [ Time Frame: Weeks 3, 6, 12, 26, 39, and 52 ] [ Designated as safety issue: No ]
    The average 60 minute post dose forced vital capacity (FVC)at visit 4, 5, 6, 7, 8 and 9 will be analyzed.
  • Time to discontinuation [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Time to premature discontinuation will be displayed graphically for each treatment group.
  • Vital signs [ Time Frame: Weeks 6, 12, 26, 39, and 52 ] [ Designated as safety issue: Yes ]
    Vital signs (blood pressure and radial pulse rate) data will be summarized by treatment at pre-dose and 30 minute post-dose time points at visits 3-9.
  • Lab values [ Time Frame: Weeks 6, 12, 26, 39, and 52 ] [ Designated as safety issue: Yes ]
    All lab data will be listed with abnormal values flagged. The lab values and the change from baseline for continuous lab parameters will be summarized at each visit. A frequency table of results for categorical lab parameters will be produced by visit. Shift tables relative to normal ranges will be used to summarize the change from baseline to post-baseline by visit.
  • Composite endpoint of all-cause mortality and serious cerebro-cardiovascular events [ Time Frame: 56 weeks ] [ Designated as safety issue: Yes ]
    A composite endpoint of all-cause mortality and serious cerebro-cardiovascular events will be analyzed.
Not Provided
Not Provided
 
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
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
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.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Chronic Obstructive Pulmonary Disease (COPD)
  • Drug: QVA149
    QVA149 110/50 µg will be supplied as capsules in blister packs for once daily inhalation using the Novartis Concept1 SDDPI
  • Drug: Tiotropium
    Tiotropium 18 µg will be supplied as capsules in blister packs for once daily inhalation using the HandiHaler SDDPI
  • Drug: 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
  • Experimental: QVA149
    Intervention: Drug: QVA149
  • Active Comparator: Tiotropium
    Intervention: Drug: Tiotropium
  • Placebo Comparator: placebo
    Intervention: Drug: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1215
February 2015
February 2015   (final data collection date for primary outcome measure)

Inclusion criteria:

  • Male and female adults aged ≥40 years.
  • Patients with stable COPD according to GOLD strategy (GOLD 2011).
  • Patients with airflow limitation indicated by a post-bronchodilator FEV1 ≥ 30% and <80% of the predicted normal, and a post-bronchodilator.
  • FEV1/FVC < 0.70.
  • Current or ex-smokers who have a smoking history of at least 10 pack years.
  • Patients with an mMRC ≥ grade 2

Exclusion criteria:

  • History of long QT syndrome or prolonged QTc.
  • Patients who have had a COPD exacerbation that required treatment with antibiotics and/or systemic corticosteroids and/or hospitalization in the 6 weeks prior to Visit 1.
  • Patients with Type I or uncontrolled Type II diabetes.
  • Patients with a history of asthma or have concomitant pulmonary disease.
  • Patients with paroxysmal (e.g. intermittent) atrial fibrillation. Only patients with persistent atrial fibrillation and controlled with a rate control strategy for at least six months could be eligible.
  • Patients who have clinically significant renal, cardiovascular, neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or hematological abnormalities which could interfere with the assessment of safety.
Both
40 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Colombia,   Croatia,   Estonia,   Hungary,   India,   Israel,   Korea, Republic of,   Latvia,   Mexico,   Panama,   Poland,   Russian Federation,   Serbia,   Slovenia,   Turkey,   United Kingdom
Dominican Republic,   Former Serbia and Montenegro,   Guatemala,   Ireland,   Lithuania
 
NCT01610037
CQVA149A2339, 2012-002057-38
Yes
Not Provided
Not Provided
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP