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

Study Overview
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Brief Summary
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Evaluate the safety and tolerability of VX-659 in healthy subjects

Official Title
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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

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: VX-659
* Drug: Tezacaftor
* Drug: Ivacaftor
* Drug: VX-659 Matching Placebo
* Drug: Triple Combination (TC) Matching Placebos


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: VX-659 or Matching Placebo<br>Part A includes single-dose escalation. | Drug: VX-659<br> <br> Drug: VX-659 Matching Placebo<br> <br> |
| Experimental: Part B: VX-659 or Matching Placebo<br>Part B includes multiple-dose escalation. | Drug: VX-659<br> <br> Drug: VX-659 Matching Placebo<br> <br> |
| Experimental: Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo<br>Part C includes multiple dose escalation of VX-659 administered in Triple Combination (TC). | Drug: VX-659<br> <br> Drug: Tezacaftor<br> <br> * Other names: TEZ;Drug: Ivacaftor<br> <br> * Other names: IVA;Drug: Triple Combination (TC) Matching Placebos<br> <br> |
| Experimental: Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo<br>Part D includes subjects with CF. Participants will receive TC or matching placebos. | Drug: VX-659<br> <br> Drug: Tezacaftor<br> <br> * Other names: TEZ;Drug: Ivacaftor<br> <br> * Other names: IVA;Drug: Triple Combination (TC) Matching Placebos<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed concentration (Cmax) of VX-659 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 | 
| 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 | 
| 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 | 
| 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 |