Cystic FibrosisPhase 2NCT01531673

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

A Phase 2 study testing VX-661 and Ivacaftor in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 36 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 12 years and older
Conditions the study is for: Cystic Fibrosis
What is being tested?: VX-661 and Ivacaftor
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 194 participants
Where: 36 sitesin 4 countries
Study dates: Feb 2012to Mar 2014
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Trial locations and contacts

36 sites in 4 countries.

Country

City, postcode or hospital

36 sites in 4 countries

United States19 sites

Vertex Investigational Site
Birmingham, Alabama
Vertex Investigational Site
Boise, Idaho
Vertex Investigational Site
Boston, Massachusetts
Vertex Investigational Site
Burlington, Vermont
Vertex Investigational Site
Chapel Hill, North Carolina
Vertex Investigational Site
Charleston, South Carolina
Vertex Investigational Site
Chicago, Illinois
Vertex Investigational Site
Cincinnati, Ohio
Vertex Investigational Site
Columbus, Ohio
Vertex Investigational Site
Grand Rapids, Michigan
Vertex Investigational Site
Hershey, Pennsylvania
Vertex Investigational Site
Kansas City, Missouri
Vertex Investigational Site
Long Branch, New Jersey
Vertex Investigational Site
New Hyde Park, New York
Vertex Investigational Site
Oakland, California
Vertex Investigational Site
Oklahoma City, Oklahoma
Vertex Investigational Site
Pittsburgh, Pennsylvania
Vertex Investigational Site
Salt Lake City, Utah
Vertex Investigational Site
Seattle, Washington

Other trials in United States

Germany8 sites

Vertex Investigational Site
Berlin
Vertex Investigational Site
Bochum
Vertex Investigational Site
Cologne, North Rhine-Westphalia
Vertex Investigational Site
Erlangen, Bavaria
Vertex Investigational Site
Frankfurt am Main, Hesse
Vertex Investigational Site
Hanover, Lower Saxony
Vertex Investigational Site
Jena
Vertex Investigational Site
Munich

Other trials in Germany

United Kingdom5 sites

Vertex Investigational Site
Cambridge, Cambridgeshire
Vertex Investigational Site
Cardiff, Vale of Glamorgen
Vertex Investigational Site
London, Greater London
Vertex Investigational Site
Manchester, Greater Manchester
Vertex Investigational Site
Southhampton, Hampshire

Other trials in United Kingdom

Canada4 sites

Vertex Investigational Site
Calgary, Alberta
Vertex Investigational Site
Halifax, Nova Scotia
Vertex Investigational Site
Toronto, Ontario
Vertex Investigational Site
Vancouver, British Columbia

Other trials in Canada

About this study

Official title: A Phase 2, Multicenter, Double-Blinded, Placebo Controlled Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-661 Monotherapy and VX-661/Ivacaftor Cotherapy in Subjects With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation

Read the detailed description

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: Cystic Fibrosis
Being tested: VX-661, Ivacaftor, Placebo matched to VX-661, Placebo matched to ivacaftor
Medical subject headings: Cystic Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VX-661Drug
IvacaftorDrug
Placebo matched to VX-661Drug
Placebo matched to ivacaftorDrug

Study groups in NCT01531673
Study group	Role	What they receive
Group 1-6d Combined: Placebo	Placebo comparator	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. Receives: Drug: Placebo matched to VX-661; Drug: Placebo matched to ivacaftor
Group 1: VX-661 10 mg qd	Experimental	All participants in group 1 who received VX-661 10 milligram (mg) tablet orally once daily (qd) for up to 28 days. Receives: Drug: VX-661
Group 2a: VX-661 30 mg qd	Experimental	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. Receives: Drug: VX-661; Drug: Placebo matched to ivacaftor
Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h	Experimental	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. Receives: Drug: VX-661; Drug: Ivacaftor
Group 3a: VX-661 100 mg qd	Experimental	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. Receives: Drug: VX-661; Drug: Placebo matched to ivacaftor
Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h	Experimental	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. Receives: Drug: VX-661; Drug: Ivacaftor
Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h	Experimental	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. Receives: Drug: VX-661; Drug: Ivacaftor
Group 5a: VX-661 150 mg qd	Experimental	All participants in group 5a who received VX-661 150 mg tablet orally qd for up to 28 days. Receives: Drug: VX-661
Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h	Experimental	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. Receives: Drug: VX-661; Drug: Ivacaftor
Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h	Experimental	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. Receives: Drug: VX-661; Drug: Ivacaftor
Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h	Experimental	All participants in group 6d who received VX-661 50 mg tablet and Ivacaftor 150 mg tablet q12h orally for up to 28 days. Receives: Drug: VX-661; Drug: Ivacaftor
Group 7: Placebo	Placebo comparator	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. Receives: Drug: Ivacaftor; Drug: Placebo matched to VX-661
Group 7: VX-661 100 mg qd	Experimental	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. Receives: Drug: VX-661; Drug: Ivacaftor

What is being measured

The primary outcome is the main question the study is designed to answer.

Safety as Determined by Adverse Events (AEs)
An AE is defined as any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the Informed Consent Form is signed. AE includes serious as well as non-serious AEs. Serious Adverse Event (SAE) is any AE that results in any of the following: death; life-threatening condition; inpatient hospitalization or prolongation of hospitalization; persistent or significant disability or incapacity; congenital anomaly or birth defect; or other important medical event. Treatment-emergent adverse events are defined as adverse events that were reported or worsened on or after start of study drug through the Follow-up Visit (28 days after last dose of study drug) or premature discontinuation.
Measured: Start of study drug through the Follow-up Visit (Up to Day 56)
Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.
Measured: Baseline through Day 28
Change in Sweat Chloride From Baseline Through Study Day 28 for Group 6
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.
Measured: Baseline through Day 28
Change in Sweat Chloride From Baseline Through Study Day 28 for Group 7
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.
Measured: Baseline through Day 28

Secondary outcomes (14)

Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.
Measured: Baseline, Day 7, Day 14, Day 21, Day 28
Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.
Measured: Baseline, Day 7, Day 14, Day 21, Day 28
Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 7
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.
Measured: Baseline, Day 7, Day 14, Day 21, Day 28
Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measured: Baseline, Day 7, Day 14, Day 21, Day 28
Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.
Measured: Baseline, Day 7, Day 14, Day 21, Day 28
Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measured: Baseline, Day 7, Day 14, Day 21, Day 28
Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measured: Baseline, Day 7, Day 14, Day 21, Day 28
Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.
Measured: Baseline, Day 7, Day 14, Day 21, Day 28
Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Measured: Baseline, Day 7, Day 14, Day 21, Day 28
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Measured: Baseline, Day 14, Day 28
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.
Measured: Baseline, Day 14, Day 28
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Measured: Baseline, Day 14, Day 28
Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 After Administration of VX-661 Monotherapy
Participants who received VX-661 monotherapy (Group 1, 2a, 3a and 5a) were analyzed for this outcome measure. PK analysis (AUC0-24h) was not planned for placebo reporting arms.
Measured: Day 28
AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor
Participants who received VX-661 in combination with Ivacaftor (Group 2b, 3b, 4, 5b, 6a, 6d and 7) were analyzed for this outcome measure. PK analysis was not planned for placebo reporting arms.
Measured: Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2012Mar 2014

First posted13 Feb 2012 (estimated)
Study startFeb 2012
Primary completionMar 2014
Study completionMar 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Cystic FibrosisStudies of the same condition, open and under way.
More trials run by Vertex Pharmaceuticals IncorporatedThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 194 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01531673
Sponsor's protocol ID: VX11-661-101
Other IDs: 2011-003821-93
Status last verified: Mar 2018
First submitted: 1 Feb 2012
Last updated: 13 Apr 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 13 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2, Multicenter, Double-Blinded, Placebo Controlled Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-661 Monotherapy and VX-661/Ivacaftor Cotherapy in Subjects With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation
ClinicalTrials.gov ID: NCT01531673
Acronym / sponsor ID: VX11-661-101
Conditions: Cystic Fibrosis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 194 participants (actual)
Lead sponsor: Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
Study start: Feb 2012
Primary completion: Mar 2014 (actual)
Study completion: Mar 2014 (actual)
First posted: 13 Feb 2012 (estimated)
Results: Posted 13 Apr 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 13

Arm	Type	Receives
Group 1-6d Combined: Placebo	Placebo comparator	Drug: Placebo matched to VX-661, Drug: Placebo matched to ivacaftorAll 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 1: VX-661 10 mg qd	Experimental	Drug: VX-661All participants in group 1 who received VX-661 10 milligram (mg) tablet orally once daily (qd) for up to 28 days.
Group 2a: VX-661 30 mg qd	Experimental	Drug: VX-661, Drug: Placebo matched to ivacaftorAll 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 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h	Experimental	Drug: VX-661, Drug: IvacaftorAll 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 3a: VX-661 100 mg qd	Experimental	Drug: VX-661, Drug: Placebo matched to ivacaftorAll 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 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h	Experimental	Drug: VX-661, Drug: IvacaftorAll 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 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h	Experimental	Drug: VX-661, Drug: IvacaftorAll 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 5a: VX-661 150 mg qd	Experimental	Drug: VX-661All participants in group 5a who received VX-661 150 mg tablet orally qd for up to 28 days.
Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h	Experimental	Drug: VX-661, Drug: IvacaftorAll 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 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h	Experimental	Drug: VX-661, Drug: IvacaftorAll 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 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h	Experimental	Drug: VX-661, Drug: IvacaftorAll participants in group 6d who received VX-661 50 mg tablet and Ivacaftor 150 mg tablet q12h orally for up to 28 days.
Group 7: Placebo	Placebo comparator	Drug: Ivacaftor, Drug: Placebo matched to VX-661All 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 7: VX-661 100 mg qd	Experimental	Drug: VX-661, Drug: IvacaftorAll 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.

Who may qualify

Ages: 12 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (5 listed)

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.

Key exclusion criteria (6 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
VX-661	Drug	Group 1: VX-661 10 mg qd, Group 2a: VX-661 30 mg qd, Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h, Group 3a: VX-661 100 mg qd, Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h, Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h, Group 5a: VX-661 150 mg qd, Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h, Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h, Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h, Group 7: VX-661 100 mg qd
Ivacaftor	Drug	Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h, Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h, Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h, Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h, Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h, Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h, Group 7: Placebo, Group 7: VX-661 100 mg qd
Placebo matched to VX-661	Drug	Group 1-6d Combined: Placebo, Group 7: Placebo
Placebo matched to ivacaftor	Drug	Group 1-6d Combined: Placebo, Group 2a: VX-661 30 mg qd, Group 3a: VX-661 100 mg qd

Primary outcome

Safety as Determined by Adverse Events (AEs)
Time frame: Start of study drug through the Follow-up Visit (Up to Day 56)
An AE is defined as any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the Informed Consent Form is signed. AE includes serious as well as non-serious AEs. Serious Adverse Event (SAE) is any AE that results in any of the following: death; life-threatening condition; inpatient hospitalization or prolongation of hospitalization; persistent or significant disability or incapacity; congenital anomaly or birth defect; or other important medical event. Treatment-emergent adverse events are defined as adverse events that were reported or worsened on or after start of study drug through the Follow-up Visit (28 days after last dose of study drug) or premature discontinuation.
Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b
Time frame: Baseline through Day 28
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.
Change in Sweat Chloride From Baseline Through Study Day 28 for Group 6
Time frame: Baseline through Day 28
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.
Change in Sweat Chloride From Baseline Through Study Day 28 for Group 7
Time frame: Baseline through Day 28
Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.

14 secondary outcomes

Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b
Time frame: Baseline, Day 7, Day 14, Day 21, Day 28
Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6
Time frame: Baseline, Day 7, Day 14, Day 21, Day 28
Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 7
Time frame: Baseline, Day 7, Day 14, Day 21, Day 28
Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b
Time frame: Baseline, Day 7, Day 14, Day 21, Day 28
Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6
Time frame: Baseline, Day 7, Day 14, Day 21, Day 28
Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7
Time frame: Baseline, Day 7, Day 14, Day 21, Day 28
Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b
Time frame: Baseline, Day 7, Day 14, Day 21, Day 28
Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6
Time frame: Baseline, Day 7, Day 14, Day 21, Day 28
Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7
Time frame: Baseline, Day 7, Day 14, Day 21, Day 28
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b
Time frame: Baseline, Day 14, Day 28
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6
Time frame: Baseline, Day 14, Day 28
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7
Time frame: Baseline, Day 14, Day 28
Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 After Administration of VX-661 Monotherapy
Time frame: Day 28
AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor
Time frame: Day 28

Results and safety

Results posted to the registry on 13 Apr 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group 1-6d Combined: Placebo	33	33
Group 1: VX-661 10 mg qd	8	7
Group 2a: VX-661 30 mg qd	8	8
Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h	18	17
Group 3a: VX-661 100 mg qd	8	7
Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h	19	18
Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h	17	17
Group 5a: VX-661 150 mg qd	9	9
Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h	17	17
Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h	19	18
Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h	16	16
Group 7: Placebo	4	4
Group 7: VX-661 100 mg qd	14	14

Primary outcome: Safety as Determined by Adverse Events (AEs)

Time frame: Start of study drug through the Follow-up Visit (Up to Day 56). Number. Unit: participants

Measure	Group 1-6d Combined: Placebo n = 33	Group 1: VX-661 10 mg qd n = 8	Group 2a: VX-661 30 mg qd n = 8	Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h n = 18	Group 3a: VX-661 100 mg qd n = 8	Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h n = 19	Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h n = 17	Group 5a: VX-661 150 mg qd n = 9	Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h n = 17	Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h n = 19	Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h n = 16	Group 7: Placebo n = 4	Group 7: VX-661 100 mg qd n = 14
Participants with AEs	30	8	7	15	7	18	10	8	17	16	16	2	12
Participants with SAEs	5	1	1	1	0	2	2	0	0	1	2	0	1

Population analysed: Analysis was done using safety set which included all participants who received at least 1 dose of study drug.

Primary outcome: Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b

Time frame: Baseline through Day 28. Least squares mean (95% Confidence Interval). Unit: millimole per liter (mmol/L)

Measure	Group 1: VX-661 10 mg qd n = 8	Group 2a: VX-661 30 mg qd n = 6	Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h n = 18	Group 3a: VX-661 100 mg qd n = 8	Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h n = 18	Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h n = 17	Group 5a: VX-661 150 mg qd n = 9	Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h n = 17	Group 1-5b Combined Placebo n = 24
Value	3.92 (-0.5 to 8.34)	-4.76 (-9.75 to 0.22)	-5.06 (-8.02 to -2.09)	-20.43 (-24.75 to -16.12)	-6 (-8.98 to 3.02)	-6.04 (-9.12 to -2.96)	-10.46 (-14.53 to -6.39)	-2.63 (-5.67 to 0.41)	-0.86 (-3.36 to 1.65)

Group 1: VX-661 10 mg qd vs Group 1-5b Combined Placebo: Least Squares (LS) Mean Difference: 4.77 (95% CI -0.3 to 9.84), p = 0.0647, Mixed-effect repeated measure (MMRM)
Group 2a: VX-661 30 mg qd vs Group 1-5b Combined Placebo: LS Mean Difference: -3.91 (95% CI -9.5 to 1.68), p = 0.1686, MMRM
Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h vs Group 1-5b Combined Placebo: LS Mean Difference: -4.2 (95% CI -8.1 to -0.31), p = 0.0348, MMRM

Population analysed: The analysis was done using Full Analysis Set (FAS) which included all randomized participants who received at least 1 dose of study drug. Here, 'Number of participants analyzed' = those participants who were evaluable for this endpoint.

Primary outcome: Change in Sweat Chloride From Baseline Through Study Day 28 for Group 6

Time frame: Baseline through Day 28. Least squares mean (95% Confidence Interval). Unit: mmol/L

Measure	Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h n = 18	Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h n = 16	Group 4 and 6 Combined: Placebo n = 14
Value	-6.07 (-10.84 to -1.31)	-7.89 (-12.3 to -3.48)	-1.19 (-5.5 to 3.12)

Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h vs Group 4 and 6 Combined: Placebo: LS Mean Difference: -6.7 (95% CI -12.94 to -0.46), p = 0.0357, MMRM

Primary outcome: Change in Sweat Chloride From Baseline Through Study Day 28 for Group 7

Time frame: Baseline through Day 28. Least squares mean (95% Confidence Interval). Unit: mmol/L

Measure	Group 7: Placebo n = 4	Group 7: VX-661 100 mg qd n = 13
Value	10.18 (-2.48 to 22.84)	-7.02 (-14.15 to 0.11)

Group 7: Placebo vs Group 7: VX-661 100 mg qd: LS Mean Difference: -17.2 (95% CI -31.75 to -2.65), p = 0.0238, MMRM

Population analysed: The analysis was done using FAS which included all randomized participants who received at least 1 dose of study drug. Here, 'Number of participants analyzed' = those participants who were evaluable for this endpoint.

14 secondary outcomes are reported in the full results.

Adverse events

Time frame: Start of study drug through the Follow-up Visit (Up to Day 56). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group 1-6d Combined: Placebo	5 of 33 (15.2%)	30 of 33 (90.9%)	Not reported
Group 1: VX-661 10 mg qd	1 of 8 (12.5%)	8 of 8 (100%)	Not reported
Group 2a: VX-661 30 mg qd	1 of 8 (12.5%)	7 of 8 (87.5%)	Not reported
Group 2b: VX-661 10 mg qd/Ivacaftor 150 mg q12h	1 of 18 (5.6%)	15 of 18 (83.3%)	Not reported
Group 3a: VX-661 100 mg qd	0 of 8 (0%)	7 of 8 (87.5%)	Not reported
Group 3b: VX-661 30 mg qd/Ivacaftor 150 mg q12h	2 of 19 (10.5%)	18 of 19 (94.7%)	Not reported
Group 4: VX-661 100 mg qd/Ivacaftor 150 mg q12h	2 of 17 (11.8%)	9 of 17 (52.9%)	Not reported
Group 5a: VX-661 150 mg qd	0 of 9 (0%)	8 of 9 (88.9%)	Not reported
Group 5b: VX-661 150 mg qd/Ivacaftor 150 mg q12h	0 of 17 (0%)	17 of 17 (100%)	Not reported
Group 6a: VX-661 100 mg qd/Ivacaftor 50 mg q12h	1 of 19 (5.3%)	16 of 19 (84.2%)	Not reported
Group 6d: VX-661 50 mg q12h/Ivacaftor 150 mg q12h	2 of 16 (12.5%)	16 of 16 (100%)	Not reported
Group 7: Placebo	0 of 4 (0%)	2 of 4 (50%)	Not reported
Group 7: VX-661 100 mg qd	1 of 14 (7.1%)	12 of 14 (85.7%)	Not reported

Limitations and caveats (from the sponsor): Pharmacokinetic (PK) final data are not yet available. Once the data are available for PK endpoints, the posting will be updated to include the same.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Scott Donaldson, MD principal investigator

University of North Carolina

36 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing VX-661 and Ivacaftor in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 36 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 36 sites in United States, Germany, United Kingdom, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety as Determined by Adverse Events (AEs) (time frame: Start of study drug through the Follow-up Visit (Up to Day 56)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01531673.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2018.