VX-695 Bioavailability Study in Healthy and Cystic Fibrosis Subjects
Research type
Research Study
Full 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
IRAS ID
214779
Contact name
Ashley Brooks
Contact email
Sponsor organisation
Vertex Pharmaceuticals Limited
Eudract number
2016-003048-35
Duration of Study in the UK
0 years, 8 months, 27 days
Research summary
Cystic fibrosis is caused by reduced quantity and/or function of the CFTR protein due to mutations in the CFTR gene. (CFTR = cystic fibrosis transmembrane conductance regulator). The CFTR protein is an epithelial chloride channel that aids in regulating salt and water absorption and secretion and pH balance in sweat glands and multiple organs, including the lungs, pancreas and other gastrointestinal organs. Two complementary approaches have been developed to address the decreased quantity and/or function of CFTR. ’Correctors’ increase the quantity of functional CFTR protein and ’Potentiators’ increase the channel open probability of the CFTR protein to enhance ion transport. This trial involves the administration of Ivacaftor (’IVA’ - a marketed CFTR potentiator), Tezacaftor (’TEZ’ - an unmarketed first-generation CFTR corrector) and VX-659 (a next generation CFTR corrector). This trial is the first time VX-659 will be administered to man both alone and in combination with IVA and IVA/TEZ.\nThis trial is split into 4 parts, A, B, C and D. Parts A to C will involve dosing in healthy volunteers and Part D will involve dosing in patients.\nPart A - SAD (single ascending dose design) - In Cohorts A1-A6, subjects will receive a single oral dose of VX-659 suspension or placebo. In Cohort A7, subjects will receive three single oral doses of VX-659 on separate days as a suspension, a tablet (to assess relative bioavailability) and as an intravenous dose (to assess absolute bioavailability).\nPart B - MAD (multiple ascending dose design) - In Cohorts B1 and B3-B6, subjects will receive multiple oral doses of VX-659 suspension or placebo for 10 days. In Cohort B2, subjects will receive multiple oral doses of VX-659 suspension or placebo for 10 days (Days 1-10) plus a dose of IVA on Day -1 and on Day 10. In Cohort B6, subjects will undergo a baseline endoscopy (camera test of the upper gastrointestinal tract) on Day -1 and a further endoscopy on Day 11 or 12 (due to gastrointestinal toxicological findings).\nPart C - Multiple dosing - In Cohorts C1 and C2, subjects will receive multiple oral doses of VX-659 suspension or placebo from Days 1-14. In addition they will receive a combination of TEZ/IVA on the mornings of Days 1-14 and a dose of IVA in the evenings of Days 1-14.\nPart D - Multiple dosing - In Part D patients will receive multiple oral doses of VX-659 suspension or placebo from Days 1-14. In addition they will receive a combination of TEZ/IVA on the mornings of Days 1-14 and a dose of IVA in the evenings of Days 1-14.
REC name
South Central - Berkshire B Research Ethics Committee
REC reference
16/SC/0497
Date of REC Opinion
7 Nov 2016
REC opinion
Further Information Favourable Opinion