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

Vertex Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Cystic Fibrosis

Treatments: Drug: Triple Combination (TC) Matching Placebos; Drug: VX-659; Drug: VX-659 Matching Placebo; Drug: Tezacaftor; Drug: Ivacaftor

Study type: Interventional

Funder types: Industry

Identifiers

NCT03029455

2016-003048-35 (EudraCT Number)

VX16-659-001

Details and patient eligibility

About

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

Enrollment: 163 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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163 participants in 4 patient groups

Part A: VX-659 or Matching Placebo

Experimental group

Description:

Part A includes single-dose escalation.

Treatment:

Drug: VX-659 Matching Placebo

Drug: VX-659

Part B: VX-659 or Matching Placebo

Experimental group

Description:

Part B includes multiple-dose escalation.

Treatment:

Drug: VX-659 Matching Placebo

Drug: VX-659

Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo

Experimental group

Description:

Part C includes multiple dose escalation of VX-659 administered in Triple Combination (TC).

Treatment:

Drug: Ivacaftor

Drug: VX-659

Drug: Tezacaftor

Drug: Triple Combination (TC) Matching Placebos

Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo

Experimental group

Description:

Part D includes subjects with CF. Participants will receive TC or matching placebos.

Treatment:

Drug: Ivacaftor

Drug: VX-659

Drug: Tezacaftor

Drug: Triple Combination (TC) Matching Placebos