A Study to Evaluate Safety and Pharmacokinetics of VX-659 in Healthy Subjects and in Adults With Cystic Fibrosis
Cystic fibrosis (CF) is an autosomal recessive chronic disease with serious morbidities and
frequent premature mortality. At present, there is no cure. CF affects approximately
70,000 individuals worldwide
The aims of the study is to evaluate the safety and tolerability of VX-659 in triple combination with TEZ/IVA for 14 days in subjects with CF
This is a randomized, double-blind, placebo-controlled, single- and multiple-dose, first-in-human dose escalation study of VX-659 that includes evaluations of relative and absolute bioavailability.
Part D (Subjects with CF)
Part D has a randomized, double-blind, placebo-controlled, parallel-group design. Approximately 12 subjects will be enrolled and randomized 3:1 to TC:placebo. Subjects will receive 14 days of treatment. Part D may be initiated while Parts A, B, and C are ongoing after review of safety, tolerability, and available PK data. The dose of VX-659 will be at least 1 dose level below the highest Part C dose for which safety and tolerability results are available and supportive. The dosage of TEZ/IVA will be TEZ 100 mg qd/IVA 150 mg q12h, which will be administered as TEZ 100-mg/IVA 150-mg FDC in
the morning and IVA 150 mg in the evening.
The decision to initiate successive cohorts and dose selection will be based on safety and tolerability data from preceding dose group(s) and available PK data from a minimum of 6 subjects (to ensure 4 subjects receiving active drug) in the preceding cohort.