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

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ClinicalTrials.gov Identifier: NCT03029455

Recruitment Status : Completed

First Posted : January 24, 2017

Last Update Posted : September 5, 2017

Sponsor:

Information provided by (Responsible Party):

Vertex Pharmaceuticals Incorporated

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

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Study Type :	Interventional (Clinical Trial)
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 :	November 2016
Actual Primary Completion Date :	August 2017
Actual Study Completion Date :	August 2017

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

Genetic and Rare Diseases Information Center resources: Cystic Fibrosis

U.S. FDA Resources

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) [ Time Frame: from baseline up to Day 50 ]

Secondary Outcome Measures :

Maximum observed concentration (Cmax) of VX-659 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 ]
Cmax of IVA and selected metabolites (μg/mL) [ Time Frame: 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) [ 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 ]
AUCtau of IVA 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 ]
Ctrough 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 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03029455

Locations

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United Kingdom

Birmingham, United Kingdom

Cambridge, United Kingdom

Exeter, United Kingdom

Glasgow, United Kingdom

Leeds, United Kingdom

Liverpool, United Kingdom

London, United Kingdom

Manchester, United Kingdom

Newcastle upon Tyne, United Kingdom

Southampton, United Kingdom

Sponsors and Collaborators

Vertex Pharmaceuticals Incorporated

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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Responsible Party:	Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:	NCT03029455 History of Changes
Other Study ID Numbers:	VX16-659-001 2016-003048-35 ( EudraCT Number )
First Posted:	January 24, 2017 Key Record Dates
Last Update Posted:	September 5, 2017
Last Verified:	September 2017

Additional relevant MeSH terms:

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Fibrosis Cystic Fibrosis Pathologic Processes Pancreatic Diseases Digestive System Diseases Lung Diseases Respiratory Tract Diseases	Genetic Diseases, Inborn Infant, Newborn, Diseases Ivacaftor Chloride Channel Agonists Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action

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