Clinical trial NCT03029455: A Study to Evaluate Safety and Pharmacokinetics of VX-659 in Healthy Subjects and in Adults With Cystic Fibrosis
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2017-01-24
Enrollment: 163
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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.

Primary outcomes:
measure: Safety and Tolerability assessments as determined by number of subjects with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: from baseline up to Day 50
Secondary outcomes:
measure: Maximum observed concentration (Cmax) of VX-659 and selected metabolites (μg/mL)
timeFrame: from baseline up to Day 18
measure: Cmax of TEZ and selected metabolites (μg/mL)
timeFrame: from baseline up to Day 18
measure: Cmax of IVA and selected metabolites (μg/mL)
timeFrame: from baseline up to Day 18
measure: Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-659 and selected metabolites (μg,h/mL)
timeFrame: from baseline up to Day 18
measure: AUCtau of TEZ and selected metabolites (μg,h/mL)
timeFrame: from baseline up to Day 18
measure: AUCtau of IVA and selected metabolites (μg,h/mL)
timeFrame: from baseline up to Day 18
measure: Observed pre-dose concentration (Ctrough) of VX-659 and selected metabolites (μg/mL)
timeFrame: from baseline up to Day 18
measure: Ctrough of TEZ and selected metabolites (μg/mL)
timeFrame: from baseline up to Day 18
measure: Ctrough of IVA and selected metabolites (μg/mL)
timeFrame: from baseline up to Day 18
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Exeter
country: United Kingdom
city: Glasgow
country: United Kingdom
city: Leeds
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Newcastle upon Tyne
country: United Kingdom
city: Southampton
country: United Kingdom
Study officials:
References:
citation: 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. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
citation: Davies 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.