Study of Ivacaftor in Cystic Fibrosis Subjects Aged 12 Years and Older Homozygous for the F508del-CFTR Mutation

A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety and Efficacy of VX-770 in Subjects Aged 12 Years and Older With Cystic Fibrosis Who Are Homozygous for the F508del-CFTR Mutation

The purpose of this study was to evaluate the safety and efficacy of ivacaftor in participants with cystic fibrosis (CF) who were aged 12 years or older and were homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation. Ivacaftor is a potent and selective CFTR 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.

This study investigated the effects of ivacaftor in participants with cystic fibrosis (CF) >=12 years of age with a forced expiratory volume in 1 second (FEV1) >=40 percent (%) predicted. This study was conducted in 2 parts.

• Part A of this study was a randomized, double-blind, placebo-controlled, parallel-group evaluation of participants with CF who were aged 12 years or older and were homozygous for the F508del-CFTR mutation.
• Part B of this study was an open-label extension of Part A, enrolling participants who completed Part A and met pre-specified endpoint criteria, and explored the safety and efficacy of ivacaftor over long-term treatment in participants with CF aged 12 years or older who were homozygous for the F508del-CFTR mutation.

Inclusion Criteria:

• Confirmed diagnosis of cystic fibrosis (CF) and homozygous for F508del-CFTR mutation
• Forced expiratory volume in 1 second (FEV1) of at least 40% of predicted normal for age, gender, and height
• Willing to use at least 2 highly effective birth control methods during the study
• No clinically significant abnormalities that would have interfered with the study assessments, as judged by the investigator
• Able to understand and comply with protocol requirements, restrictions, and instructions and likely to complete the study as planned, 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
• History of alcohol, medication or illicit drug abuse within one year prior to Day 1
• Abnormal liver function >=3 x the upper limit of normal
• Abnormal renal function at Screening
• History of solid organ or hematological transplantation
• Pregnant or breast-feeding (for women)
• Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days prior to screening
• Previous participation in a VX-809 study
• Used inhaled hypertonic saline treatment
• Concomitant use of any inhibitors or inducers of cytochrome P450 3A4 (CYP3A4)