Study of VX-661 Alone and in Combination With Ivacaftor in Subjects Homozygous or Heterozygous to the F508del-Cystic Fibrosis Transmembrane Conductance Regulator(CFTR) Mutation

NCT ID: NCT01531673

Last Updated: 2018-04-13

Study Results

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Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

194 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-02-29

Study Completion Date

2014-03-31

Brief Summary

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The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) effects of VX-661 alone and when coadministered with ivacaftor in participants with cystic fibrosis (CF) who are homozygous or heterozygous for the F508del-CFTR mutation.

Detailed Description

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This is a Phase 2, randomized, multicenter, double-blinded, placebo-controlled, study of VX-661 monotherapy, and VX-661/ivacaftor co-therapy in participants with CF who are homozygous or heterozygous for the F508del CFTR mutation.

This study is separated into seven groups: Group 1-7, respectively. Approximately 180 participants were randomized in a ratio of 4:1; active drug to matching placebo in each group.

Conditions

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Cystic Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Group 1-6d Combined: Placebo

All participants in group 1, 2a, 2b, 3a, 3b, 4, 5a, 5b, 6a and 6d who received placebo matched to VX-661 tablet and/or placebo matched to ivacaftor tablet for up to 28 days.

Group Type PLACEBO_COMPARATOR

Placebo matched to VX-661

Intervention Type DRUG

Placebo matched to ivacaftor

Intervention Type DRUG

Group 1: VX-661 10 mg qd

All participants in group 1 who received VX-661 10 milligram (mg) tablet orally once daily (qd) for up to 28 days.

Group Type EXPERIMENTAL

VX-661

Intervention Type DRUG

Group 2a: VX-661 30 mg qd

All participants in group 2a who received VX-661 30 mg tablet orally qd and placebo matched to Ivacaftor tablet every 12 hours (q12h) for up to 28 days.

Group Type EXPERIMENTAL

VX-661

Intervention Type DRUG

Placebo matched to ivacaftor

Intervention Type DRUG

Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h

All participants in group 2b who received VX-661 10 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.

Group Type EXPERIMENTAL

VX-661

Intervention Type DRUG

Ivacaftor

Intervention Type DRUG

Group 3a: VX-661 100 mg qd

All participants in group 3a who received VX-661 100 mg tablet orally qd and placebo matched to Ivacaftor tablet q12h for up to 28 days.

Group Type EXPERIMENTAL

VX-661

Intervention Type DRUG

Placebo matched to ivacaftor

Intervention Type DRUG

Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h

All participants in group 3b who received VX-661 30 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.

Group Type EXPERIMENTAL

VX-661

Intervention Type DRUG

Ivacaftor

Intervention Type DRUG

Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h

All participants in group 4 who received VX-661 100 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.

Group Type EXPERIMENTAL

VX-661

Intervention Type DRUG

Ivacaftor

Intervention Type DRUG

Group 5a: VX-661 150 mg qd

All participants in group 5a who received VX-661 150 mg tablet orally qd for up to 28 days.

Group Type EXPERIMENTAL

VX-661

Intervention Type DRUG

Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h

All participants in group 5b who received VX-661 150 mg tablet qd and Ivacaftor 150 mg tablet q12h orally for up to 28 days.

Group Type EXPERIMENTAL

VX-661

Intervention Type DRUG

Ivacaftor

Intervention Type DRUG

Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h

All participants in group 6a who received VX-661 100 mg tablet qd and Ivacaftor 50 mg tablet q12h orally for up to 28 days.

Group Type EXPERIMENTAL

VX-661

Intervention Type DRUG

Ivacaftor

Intervention Type DRUG

Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h

All participants in group 6d who received VX-661 50 mg tablet and Ivacaftor 150 mg tablet q12h orally for up to 28 days.

Group Type EXPERIMENTAL

VX-661

Intervention Type DRUG

Ivacaftor

Intervention Type DRUG

Group 7: Placebo

All participants in group 7 who received placebo matched to VX-661 tablet orally qd in combination with physician-prescribed Kalydeco (Ivacaftor) for up to 28 days.

Group Type PLACEBO_COMPARATOR

Ivacaftor

Intervention Type DRUG

Placebo matched to VX-661

Intervention Type DRUG

Group 7: VX-661 100 mg qd

All participants in group 7 who received VX-661 100 mg tablet orally qd in combination with physician-prescribed Kalydeco (Ivacaftor) for up to 28 days.

Group Type EXPERIMENTAL

VX-661

Intervention Type DRUG

Ivacaftor

Intervention Type DRUG

Interventions

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VX-661

Intervention Type DRUG

Ivacaftor

Intervention Type DRUG

Placebo matched to VX-661

Intervention Type DRUG

Placebo matched to ivacaftor

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Male or female with confirmed diagnosis of CF
* Must have the F508del-CFTR gene mutation in both alleles (Groups 1, 2, 3, 4, 5, 6). Group 7 participants must have the F508del-CFTR mutation on 1 allele, and gating mutation G551D on the second allele and have been on their physician prescribed 150 mg KalydecoTM q12h (commercially available ivacaftor) for at least 28 days at the Screening Visit.
* Forced expiratory volume in 1 second(FEV1) 40% to 90% (inclusive) of predicted normal for age, gender, and height (Knudson standards) at screening
* Weight \>40 kg and BMI \>18.5
* Participants of child-bearing potential and who are sexually active must meet the contraception requirements.

Exclusion Criteria

* History of any illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant.
* An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Study Day 1.
* History of solid organ or hematological transplantation
* Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever is longer) before screening
* History of alcohol, medication, or illicit drug abuse within 1 year prior to screening
* Pregnant, breast-feeding, or not willing to follow contraception requirements
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vertex Pharmaceuticals Incorporated

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Scott Donaldson, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina

Locations

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Vertex Investigational Site

Birmingham, Alabama, United States

Site Status

Vertex Investigational Site

Oakland, California, United States

Site Status

Vertex Investigational Site

Boise, Idaho, United States

Site Status

Vertex Investigational Site

Chicago, Illinois, United States

Site Status

Vertex Investigational Site

Boston, Massachusetts, United States

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Vertex Investigational Site

Grand Rapids, Michigan, United States

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Vertex Investigational Site

Kansas City, Missouri, United States

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Vertex Investigational Site

Long Branch, New Jersey, United States

Site Status

Vertex Investigational Site

New Hyde Park, New York, United States

Site Status

Vertex Investigational Site

Chapel Hill, North Carolina, United States

Site Status

Vertex Investigational Site

Cincinnati, Ohio, United States

Site Status

Vertex Investigational Site

Columbus, Ohio, United States

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Vertex Investigational Site

Oklahoma City, Oklahoma, United States

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Vertex Investigational Site

Hershey, Pennsylvania, United States

Site Status

Vertex Investigational Site

Pittsburgh, Pennsylvania, United States

Site Status

Vertex Investigational Site

Charleston, South Carolina, United States

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Vertex Investigational Site

Salt Lake City, Utah, United States

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Vertex Investigational Site

Burlington, Vermont, United States

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Vertex Investigational Site

Seattle, Washington, United States

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Vertex Investigational Site

Calgary, Alberta, Canada

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Vertex Investigational Site

Vancouver, British Columbia, Canada

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Vertex Investigational Site

Halifax, Nova Scotia, Canada

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Vertex Investigational Site

Toronto, Ontario, Canada

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Vertex Investigational Site

Erlangen, Bavaria, Germany

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Vertex Investigational Site

Frankfurt am Main, Hesse, Germany

Site Status

Vertex Investigational Site

Hanover, Lower Saxony, Germany

Site Status

Vertex Investigational Site

Cologne, North Rhine-Westphalia, Germany

Site Status

Vertex Investigational Site

Berlin, , Germany

Site Status

Vertex Investigational Site

Bochum, , Germany

Site Status

Vertex Investigational Site

Jena, , Germany

Site Status

Vertex Investigational Site

Munich, , Germany

Site Status

Vertex Investigational Site

Cambridge, Cambridgeshire, United Kingdom

Site Status

Vertex Investigational Site

London, Greater London, United Kingdom

Site Status

Vertex Investigational Site

Manchester, Greater Manchester, United Kingdom

Site Status

Vertex Investigational Site

Southhampton, Hampshire, United Kingdom

Site Status

Vertex Investigational Site

Cardiff, Vale of Glamorgen, United Kingdom

Site Status

Countries

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United States Canada Germany United Kingdom

Other Identifiers

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2011-003821-93

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VX11-661-101

Identifier Type: -

Identifier Source: org_study_id

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