Cystic Fibrosis
Conditions
Brief summary
Evaluate the safety and tolerability of VX-659 in healthy subjects
Interventions
DRUGVX-659
DRUGTezacaftor
DRUGIvacaftor
DRUGVX-659 Matching Placebo
DRUGTriple Combination (TC) Matching Placebos
Sponsors
Vertex Pharmaceuticals Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and Tolerability assessments as determined by number of subjects with adverse events (AEs) and serious adverse events (SAEs) | from baseline up to Day 50 |
Secondary
| Measure | Time frame |
|---|---|
| Cmax of TEZ and selected metabolites (μg/mL) | from baseline up to Day 18 |
| Cmax of IVA and selected metabolites (μg/mL) | from baseline up to Day 18 |
| Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-659 and selected metabolites (μg,h/mL) | from baseline up to Day 18 |
| AUCtau of TEZ and selected metabolites (μg,h/mL) | from baseline up to Day 18 |
| Maximum observed concentration (Cmax) of VX-659 and selected metabolites (μg/mL) | from baseline up to Day 18 |
| Observed pre-dose concentration (Ctrough) of VX-659 and selected metabolites (μg/mL) | from baseline up to Day 18 |
| Ctrough of TEZ and selected metabolites (μg/mL) | from baseline up to Day 18 |
| Ctrough of IVA and selected metabolites (μg/mL) | from baseline up to Day 18 |
| AUCtau of IVA and selected metabolites (μg,h/mL) | from baseline up to Day 18 |
Countries
United Kingdom
Outcome results
None listed