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

Primary Purpose

Cystic Fibrosis

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

VX-659

Tezacaftor

Ivacaftor

VX-659 Matching Placebo

Triple Combination (TC) Matching Placebos

About this trial

This is an interventional treatment trial for Cystic Fibrosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Part A: VX-659 or Matching Placebo

Part B: VX-659 or Matching Placebo

Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo

Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo

Arm Description

Part A includes single-dose escalation.

Part B includes multiple-dose escalation.

Part C includes multiple dose escalation of VX-659 administered in Triple Combination (TC).

Part D includes subjects with CF. Participants will receive TC or matching placebos.

Outcomes

Primary Outcome Measures

Safety and Tolerability assessments as determined by number of subjects with adverse events (AEs) and serious adverse events (SAEs)

Secondary Outcome Measures

Maximum observed concentration (Cmax) of VX-659 and selected metabolites (μg/mL)

Cmax of TEZ and selected metabolites (μg/mL)

Cmax of IVA and selected metabolites (μg/mL)

Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-659 and selected metabolites (μg,h/mL)

AUCtau of TEZ and selected metabolites (μg,h/mL)

AUCtau of IVA and selected metabolites (μg,h/mL)

Observed pre-dose concentration (Ctrough) of VX-659 and selected metabolites (μg/mL)

Ctrough of TEZ and selected metabolites (μg/mL)

Ctrough of IVA and selected metabolites (μg/mL)

Full Information

NCT ID

NCT03029455

First Posted

January 11, 2017

Last Updated

September 1, 2017

Sponsor

Vertex Pharmaceuticals Incorporated

1. Study Identification

Unique Protocol Identification Number

NCT03029455

Brief Title

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

2. Study Status

Record Verification Date

September 2017

Overall Recruitment Status

Completed

Study Start Date

November 2016 (undefined)

Primary Completion Date

August 2017 (Actual)

Study Completion Date

August 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Vertex Pharmaceuticals Incorporated

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cystic Fibrosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

163 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part A: VX-659 or Matching Placebo

Arm Type

Experimental

Arm Description

Part A includes single-dose escalation.

Arm Title

Part B: VX-659 or Matching Placebo

Arm Type

Experimental

Arm Description

Part B includes multiple-dose escalation.

Arm Title

Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo

Arm Type

Experimental

Arm Description

Part C includes multiple dose escalation of VX-659 administered in Triple Combination (TC).

Arm Title

Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo

Arm Type

Experimental

Arm Description

Part D includes subjects with CF. Participants will receive TC or matching placebos.

Intervention Type

Drug

Intervention Name(s)

VX-659

Intervention Type

Drug

Intervention Name(s)

Tezacaftor

Other Intervention Name(s)

VX-661, TEZ

Intervention Type

Drug

Intervention Name(s)

Ivacaftor

Other Intervention Name(s)

VX-770, IVA

Intervention Type

Drug

Intervention Name(s)

VX-659 Matching Placebo

Intervention Type

Drug

Intervention Name(s)

Triple Combination (TC) Matching Placebos

Primary Outcome Measure Information:

Title

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 Measure Information:

Title

Maximum observed concentration (Cmax) of VX-659 and selected metabolites (μg/mL)

Time Frame

from baseline up to Day 18

Title

Cmax of TEZ and selected metabolites (μg/mL)

Time Frame

from baseline up to Day 18

Title

Cmax of IVA and selected metabolites (μg/mL)

Time Frame

from baseline up to Day 18

Title

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

Title

AUCtau of TEZ and selected metabolites (μg,h/mL)

Time Frame

from baseline up to Day 18

Title

AUCtau of IVA and selected metabolites (μg,h/mL)

Time Frame

from baseline up to Day 18

Title

Observed pre-dose concentration (Ctrough) of VX-659 and selected metabolites (μg/mL)

Time Frame

from baseline up to Day 18

Title

Ctrough of TEZ and selected metabolites (μg/mL)

Time Frame

from baseline up to Day 18

Title

Ctrough of IVA and selected metabolites (μg/mL)

Time Frame

from baseline up to Day 18

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Facility Information:

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

12. IPD Sharing Statement

Citations:

PubMed Identifier

33331662

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.

Results Reference

derived

PubMed Identifier

30334693

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.

Results Reference

derived

Learn more about this trial

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

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