A Phase 3, 2-Part, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Pharmacokinetics, Efficacy and Safety of VX-770 in Subjects Aged 6 to 11 Years With Cystic Fibrosis and the G551D Mutation
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Cystic Fibrosis
- Sponsor
- Vertex Pharmaceuticals Incorporated
- Enrollment
- 52
- Locations
- 29
- Primary Endpoint
- Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
The purpose of this study was to evaluate the efficacy and safety of ivacaftor in subjects with cystic fibrosis aged 6 to 11 years who have the G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Ivacaftor is a potent and selective potentiator of wild-type, G551D, F508del, and R117H forms of human CFTR protein. Potentiators are pharmacological agents that increase the chloride ion transport properties of the channel in the presence of cyclic adenosine monophosphate (AMP)-dependent protein kinase A (PKA) activation.
Detailed Description
This is a Phase 3, 2-part, randomized, double-blind, placebo-controlled, parallel group multicenter study of orally administered ivacaftor in subjects with cystic fibrosis (CF) 6 to 11 years of age who have the G551D-CFTR mutation and a forced expiratory volume in 1 second (FEV1) between 90% and 105% predicted (using Knudson standards). Based on in vitro studies and pharmacologic, pharmacokinetic (PK), and safety profiles, ivacaftor was selected for clinical development as a possible treatment for patients with CF. Patients with the G551D mutation were the targeted population for this study because ivacaftor is a potentiator of the gating effect of the CFTR protein, and the most prevalent mutation with a gating defect in CF is the G551D mutation. This study was conducted in 2 parts. Part A was conducted to analyze the PK properties of ivacaftor and to determine the most appropriate dose to administer to subjects in Part B of this study. Part B explored the safety and efficacy of ivacaftor over long-term treatment in subjects 6 to 11 years of age.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Weighing at least 15 kg
- •Confirmed diagnosis of cystic fibrosis (CF) and G551D mutation in at least 1 allele
- •Forced expiratory volume in 1 second (FEV1) of 40% to 105% (inclusive) of predicted normal for age, gender, and height (Knudson standards) at Screening
- •Able to swallow tablets
- •As judged by the investigator, parent or legal guardian and subject must have been able to understand protocol requirements, restrictions, and instructions, and the parent or legal guardian should have been able to ensure that the subject complied with, and was likely to complete, the study as planned
- •Parent or legal guardian must have signed the informed consent form and corresponding assent must be obtained from the subject
- •Willing to use at least 1 highly effective birth control method during the study
- •No clinically significant abnormalities that would have interfered with the study assessments, as judged by the investigator
Exclusion Criteria
- •History of any illness or condition that might confound the results of the study or pose an additional risk in administering study drug to the subject
- •Acute respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks of Day 1 of the study
- •Abnormal liver function ≥ 3x the upper limit of normal
- •Abnormal renal function at Screening
- •History of solid organ or hematological transplantation
- •Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days prior to Screening
- •Use of inhaled hypertonic saline treatment
- •Concomitant use of any inhibitors or inducers of cytochrome P450 3A4 (CYP 3A4)
Arms & Interventions
Placebo
Subjects who received placebo every 12 hours (q12h) for up to 48 weeks.
Intervention: Placebo
150 mg Ivacaftor q12h
Subjects who received 150 mg of ivacaftor q12h for up to 48 weeks.
Intervention: Ivacaftor
Outcomes
Primary Outcomes
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 24
Time Frame: baseline through 24 weeks
Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.
Secondary Outcomes
- Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 48(baseline through 48 weeks)
- Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Through Week 24 and Week 48 (Respiratory Domain Score, Children)(baseline through 24 weeks and 48 weeks)
- Absolute Change From Baseline in Sweat Chloride Concentration Through Week 24 and Week 48(baseline through 24 weeks and 48 weeks)
- Absolute Change From Baseline in Weight at Week 24 and Week 48(baseline to 24 weeks and 48 weeks)