Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Lumacaftor in Combination With Ivacaftor
- Registration Number
- NCT02544451
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
Study 110 is a Phase 3, multicenter study in subjects aged 6 years and older with cystic fibrosis (CF) who are homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation and who participated in Study 109 (NCT02514473) or Study 011B (NCT01897233). Study 110 is designed to evaluate the safety and efficacy of long term treatment of lumacaftor in combination with ivacaftor.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 246
Subjects entering the Treatment Cohort must meet both of the following criteria:
- Completed study visits up to Week 24 of Study 109 or Week 26 of Study 011B and did not permanently discontinue treatment
- Willing to remain on a stable CF medication through the Safety Follow-up Visit.
Subjects entering the Observational Cohort must meet 1 of the following criteria:
- Completed 24 weeks of study drug treatment in Study 109 or completed 24 weeks of study drug treatment and the Week 26 Safety Follow up in Study 011B.
- Received at least 4 weeks of study drug and completed visits up to Week 24 of Study 109 or Week 26 of Study 011B.
Exclusion Criteria (Treatment Cohort Only):
- History of any comorbidity or laboratory abnormality that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject (e.g., cirrhosis with portal hypertension).
- Pregnant and nursing females.
- Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements.
- History of drug intolerance in the prior study that would pose an additional risk to the subject in the opinion of investigator
- History of poor compliance with study drug and/or procedure in the previous study as deemed by the investigator.
- Participation in an investigational drug trial (including studies investigating lumacaftor and/or ivacaftor).
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment Period 1: Placebo (PBO) to LUM/IVA LUM/IVA - Treatment Period 1: LUM/IVA to LUM/IVA LUM/IVA - Treatment Period 2: LUM/IVA LUM/IVA -
- Primary Outcome Measures
Name Time Method Treatment Period 1 (Treatment Cohorts): Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Day 1 up to Week 100
- Secondary Outcome Measures
Name Time Method Absolute Change in Weight From Parent Study Baseline at Week 96 Absolute Change in Height-for-age Z-score From Parent Study Baseline at Week 96 z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Time-to-first Pulmonary Exacerbation From Parent Study Baseline through Week 96 Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Number of Pulmonary Exacerbation Events Per Patient-year From Parent Study Baseline through Week 96 Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Observational Cohort: Safety as Assessed by Serious Adverse Events (SAEs) Day 1 up to Week 100 Absolute Change in Body Mass Index (BMI) From Parent Study Baseline at Week 96 BMI was defined as weight in kilograms divided by height in square meter (m\^2).
Rate of Change in ppFEV1 Day 15 after first dose of LUM/IVA through Week 96 Rate of change analysis evaluates the change in ppFEV1 after long term treatment with LUM/IVA. A rate of change equal to zero would indicate that treatment effects were stable.
Absolute Change in BMI-for-age Z-score From Parent Study Baseline at Week 96 BMI was defined as weight in kilograms divided by height in m\^2. z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Absolute Change in Sweat Chloride From Parent Study Baseline at Week 96 Sweat samples were collected using an approved collection device.
Absolute Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Total Domain Score From Parent Study Baseline at Week 96 The TSQM measures participants' experiences with their medication on four dimensions: effectiveness, side effects, convenience and global satisfaction. For each dimension, responses are added and transformed in the total domain score, which ranges from 0 to 100, where higher scores indicate greater satisfaction.
Rate of Change in LCI 2.5 Day 15 after first dose of LUM/IVA through Week 96 Rate of change analysis evaluates the change in LCI 2.5 after long term treatment with LUM/IVA. A rate of change equal to zero would indicate that treatment effects were stable.
Rate of Change in LCI 5.0 Day 15 after first dose of LUM/IVA through Week 96 Rate of change analysis evaluates the change in LCI 5.0 after long term treatment with LUM/IVA. A rate of change equal to zero would indicate that treatment effects were stable.
Absolute Change in Lung Clearance Index (LCI) 2.5 From Parent Study Baseline at Week 96 LCI 2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Parent Study Baseline at Week 96 The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Absolute Change in LCI 5.0 From Parent Study Baseline at Week 96 LCI 5.0 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/20th of its starting value.
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Parent Study Baseline at Week 96 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Relative Change in ppFEV1 From Parent Study Baseline at Week 96 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Absolute Change in Height From Parent Study Baseline at Week 96 Treatment Period 2: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) Day 1 up to Week 168 Absolute Change in Weight-for-age Z-score From Parent Study Baseline at Week 96 z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Percentage of Participants Having At Least 1 Pulmonary Exacerbation Event From Parent Study Baseline through Week 96 Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.