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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT03029455
• Date of registration: 11/01/2017
• Prospective Registration: No
• Primary sponsor: Vertex Pharmaceuticals Incorporated
• Public title: A Study to Evaluate Safety and Pharmacokinetics of VX-659 in Healthy Subjects and in Adults With Cystic Fibrosis
• Scientific title: 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
• Date of first enrolment: November 2016
• Target sample size: 163
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03029455
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 1

Countries of recruitment

United Kingdom

Key inclusion & exclusion criteria

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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Drug: Tezacaftor

Drug: VX-659

Drug: Triple Combination (TC) Matching Placebos

Drug: VX-659 Matching Placebo

Drug: Ivacaftor

Primary Outcome(s)

Safety and Tolerability assessments as determined by number of subjects with adverse events (AEs) and serious adverse events (SAEs) [Time Frame: from baseline up to Day 50]

Secondary Outcome(s)

Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-659 and selected metabolites (µg,h/mL) [Time Frame: from baseline up to Day 18]

Observed pre-dose concentration (Ctrough) of VX-659 and selected metabolites (µg/mL) [Time Frame: from baseline up to Day 18]

AUCtau of TEZ and selected metabolites (µg,h/mL) [Time Frame: from baseline up to Day 18]

Ctrough of TEZ and selected metabolites (µg/mL) [Time Frame: from baseline up to Day 18]

AUCtau of IVA and selected metabolites (µg,h/mL) [Time Frame: from baseline up to Day 18]

Cmax of IVA and selected metabolites (µg/mL) [Time Frame: from baseline up to Day 18]

Cmax of TEZ and selected metabolites (µg/mL) [Time Frame: from baseline up to Day 18]

Ctrough of IVA and selected metabolites (µg/mL) [Time Frame: from baseline up to Day 18]

Maximum observed concentration (Cmax) of VX-659 and selected metabolites (µg/mL) [Time Frame: from baseline up to Day 18]

Secondary ID(s)

VX16-659-001

2016-003048-35

Source(s) of Monetary Support

Please refer to primary and secondary sponsors