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

Sponsor

Vertex Pharmaceuticals Incorporated (Industry)

Overall Status

Completed

CT.gov ID

NCT03029455

Collaborator

(none)

163

Enrollment

Locations

Arms

Duration (Months)

16.3

Patients Per Site

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: VX-659 Drug: Tezacaftor Drug: Ivacaftor Drug: VX-659 Matching Placebo Drug: Triple Combination (TC) Matching Placebos	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

163 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official 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

Study Start Date :

Nov 1, 2016

Actual Primary Completion Date :

Aug 1, 2017

Actual Study Completion Date :

Aug 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: VX-659 or Matching Placebo Part A includes single-dose escalation.	Drug: VX-659 Drug: VX-659 Matching Placebo
Experimental: Part B: VX-659 or Matching Placebo Part B includes multiple-dose escalation.	Drug: VX-659 Drug: VX-659 Matching Placebo
Experimental: Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo Part C includes multiple dose escalation of VX-659 administered in Triple Combination (TC).	Drug: VX-659 Drug: Tezacaftor Other Names: VX-661 TEZ Drug: Ivacaftor Other Names: VX-770 IVA Drug: Triple Combination (TC) Matching Placebos
Experimental: Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo Part D includes subjects with CF. Participants will receive TC or matching placebos.	Drug: VX-659 Drug: Tezacaftor Other Names: VX-661 TEZ Drug: Ivacaftor Other Names: VX-770 IVA Drug: Triple Combination (TC) Matching Placebos

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	City	Country
1	Birmingham	United Kingdom
2	Cambridge	United Kingdom
3	Exeter	United Kingdom
4	Glasgow	United Kingdom
5	Leeds	United Kingdom
6	Liverpool	United Kingdom
7	London	United Kingdom
8	Manchester	United Kingdom
9	Newcastle upon Tyne	United Kingdom
10	Southampton	United Kingdom

Sponsors and Collaborators

Vertex Pharmaceuticals Incorporated

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Vertex Pharmaceuticals Incorporated

ClinicalTrials.gov Identifier:

NCT03029455

Other Study ID Numbers:

VX16-659-001
2016-003048-35

First Posted:

Jan 24, 2017

Last Update Posted:

Sep 5, 2017

Last Verified:

Sep 1, 2017

Additional relevant MeSH terms:

Study Results

No Results Posted as of Sep 5, 2017