A Study to Evaluate Safety and Pharmacokinetics of VX-659 in Healthy Subjects and in Adults With Cystic Fibrosis
Phase 1
Completed
- Conditions
- Cystic Fibrosis
- Interventions
- Drug: VX-659 Matching PlaceboDrug: Triple Combination (TC) Matching Placebos
- Registration Number
- NCT03029455
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
Evaluate the safety and tolerability of VX-659 in healthy subjects
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 163
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: VX-659 or Matching Placebo VX-659 Matching Placebo Part A includes single-dose escalation. Part B: VX-659 or Matching Placebo VX-659 Part B includes multiple-dose escalation. Part B: VX-659 or Matching Placebo VX-659 Matching Placebo Part B includes multiple-dose escalation. Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo VX-659 Part C includes multiple dose escalation of VX-659 administered in Triple Combination (TC). Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo Tezacaftor Part C includes multiple dose escalation of VX-659 administered in Triple Combination (TC). Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo Ivacaftor Part C includes multiple dose escalation of VX-659 administered in Triple Combination (TC). Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo Triple Combination (TC) Matching Placebos Part C includes multiple dose escalation of VX-659 administered in Triple Combination (TC). Part A: VX-659 or Matching Placebo VX-659 Part A includes single-dose escalation. Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo Ivacaftor Part D includes subjects with CF. Participants will receive TC or matching placebos. Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo Triple Combination (TC) Matching Placebos Part D includes subjects with CF. Participants will receive TC or matching placebos. Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo VX-659 Part D includes subjects with CF. Participants will receive TC or matching placebos. Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo Tezacaftor Part D includes subjects with CF. Participants will receive TC or matching placebos.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Maximum observed concentration (Cmax) of VX-659 and selected metabolites (μg/mL) from baseline up to Day 18 AUCtau of TEZ and selected metabolites (μg,h/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 Cmax of TEZ 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 Observed pre-dose concentration (Ctrough) of VX-659 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