A Study to Evaluate Safety and Pharmacokinetics of VX-659 in Healthy Subjects and in Adults With Cystic Fibrosis

A Phase 1, Randomized, Double Blind, Placebo Controlled, Dose Escalation, and Bioavailability Study Evaluating the Safety and Pharmacokinetics of VX-659 in Healthy Subjects and in Subjects With Cystic Fibrosis

Evaluate the safety and tolerability of VX-659 in healthy subjects

Inclusion Criteria:

Healthy Volunteers: PARTS A, B, and C

• Males and Females of non-childbearing potential.
• Between the ages of 18 and 60 years inclusive
• Healthy, as defined per protocol.
• Body mass index (BMI) of 18.0 to 32.0 kg/m2 inclusive
• Body weight >50 kg

CF Patients: PART D

• Body weight ≥35 kg.
• Males and Females of non-childbearing potential.
• Sweat chloride value ≥ 60 mmol/L at screening.
• Heterozygous for F508del and a minimal function CFTR mutation
• Forced expiratory volume in 1 second (FEV1) ≥40% and ≤90% of predicted at screening

Exclusion Criteria:

Healthy Volunteers: PARTS A, B, and C

• History of any illness or any clinical condition that in the opinion of the investigator might confound the results of the study or pose additional risk to the subject.
• Any condition possibly affecting drug absorption.
• History of febrile illness within 14 days before the first study drug dose.
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.

CF Patients: PART D

• History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the subject.
• History of cirrhosis with portal hypertension.
• Risk factors for Torsade de Pointes.
• G6PD deficiency assessed at Screening.
• Abnormal Laboratory Values.
• Lung infection with organisms associated with a more rapid decline in pulmonary status
• History of solid organ or hematological transplantation.