A Study to Evaluate Safety and Pharmacokinetics of VX-659 in Healthy Subjects and in Adults With Cystic Fibrosis
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
2 other identifiers
interventional
163
1 country
10
Brief Summary
Evaluate the safety and tolerability of VX-659 in healthy subjects
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Nov 2016
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2016
CompletedFirst Submitted
Initial submission to the registry
January 11, 2017
CompletedFirst Posted
Study publicly available on registry
January 24, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2017
CompletedSeptember 5, 2017
September 1, 2017
9 months
January 11, 2017
September 1, 2017
Conditions
Outcome Measures
Primary Outcomes (1)
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 Outcomes (9)
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
- +4 more secondary outcomes
Study Arms (4)
Part A: VX-659 or Matching Placebo
EXPERIMENTALPart A includes single-dose escalation.
Part B: VX-659 or Matching Placebo
EXPERIMENTALPart B includes multiple-dose escalation.
Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
EXPERIMENTALPart C includes multiple dose escalation of VX-659 administered in Triple Combination (TC).
Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo
EXPERIMENTALPart D includes subjects with CF. Participants will receive TC or matching placebos.
Interventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (10)
Unknown Facility
Birmingham, United Kingdom
Unknown Facility
Cambridge, United Kingdom
Unknown Facility
Exeter, United Kingdom
Unknown Facility
Glasgow, United Kingdom
Unknown Facility
Leeds, United Kingdom
Unknown Facility
Liverpool, United Kingdom
Unknown Facility
London, United Kingdom
Unknown Facility
Manchester, United Kingdom
Unknown Facility
Newcastle upon Tyne, United Kingdom
Unknown Facility
Southampton, United Kingdom
Related Publications (3)
Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.
PMID: 37983082DERIVEDSouthern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
PMID: 33331662DERIVEDDavies JC, Moskowitz SM, Brown C, Horsley A, Mall MA, McKone EF, Plant BJ, Prais D, Ramsey BW, Taylor-Cousar JL, Tullis E, Uluer A, McKee CM, Robertson S, Shilling RA, Simard C, Van Goor F, Waltz D, Xuan F, Young T, Rowe SM; VX16-659-101 Study Group. VX-659-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles. N Engl J Med. 2018 Oct 25;379(17):1599-1611. doi: 10.1056/NEJMoa1807119. Epub 2018 Oct 18.
PMID: 30334693DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 11, 2017
First Posted
January 24, 2017
Study Start
November 1, 2016
Primary Completion
August 1, 2017
Study Completion
August 1, 2017
Last Updated
September 5, 2017
Record last verified: 2017-09