Study of VX-661 Alone and in Combination With VX-770 in Subjects Homozygous to the F508del-CFTR Mutation - Full Text View

Purpose

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 VX-770 in subjects with CF who are homozygous for the F508del-CFTR mutation.

Condition	Intervention	Phase
Cystic Fibrosis	Drug: VX-661 Drug: VX-770 Drug: VX-661 placebo Drug: VX-770 placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase 2, Multicenter, Double-Blinded, Placebo Controlled, 3-Part Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-661 Monotherapy and VX-661/VX-770 Cotherapy in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation

Resource links provided by NLM:

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis Sweat

Drug Information available for: Ivacaftor

U.S. FDA Resources

Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:

Safety and tolerability of active drug vs placebo [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
Measured by incidence of treatment-emergent adverse events
Safety and tolerability of active drug vs placebo [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
Measured by clinical laboratory values (serum chemistry, hematology, coagulation studies, and urinalysis)
Safety and tolerability of active drug vs placebo [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
Measured by 12-lead ECG outcomes
Safety and tolerability of active drug vs placebo [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
Measured by vital signs
Absolute change in sweat chloride [ Time Frame: From baseline across all visits through Day 28 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in sweat chloride [ Time Frame: From baseline to each visit up to Day 28 ] [ Designated as safety issue: No ]
Change in percent predicted forced expiratory volume in 1 second [ Time Frame: From baseline through Day 28 ] [ Designated as safety issue: No ]
Change in forced expiratory volume in 1 second [ Time Frame: From baseline to each visit and from baseline through Day 28 ] [ Designated as safety issue: No ]
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score [ Time Frame: From baseline to each visit up to Day 28 ] [ Designated as safety issue: No ]
Maximum plasma concentration (Cmax) of VX-661, VX-770, and their respective metabolites in plasma when VX-661 is administered alone and when the 2 drugs are administered together. [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
PK blood samples will be drawn on Days 1, 7, 14, 21, 28, 35, 42, and at the follow-up visit.
Minimum plasma concentration (Cmin) of VX-661, VX-770, and their respective metabolites in plasma when VX-661 is administered alone and when the 2 drugs are administered together. [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
PK blood samples will be drawn on Days 1, 7, 14, 21, 28, 35, 42, and at the follow-up visit.
Average plasma concentration (Cavg) of VX-661, VX-770, and their respective metabolites in plasma when VX-661 is administered alone and when the 2 drugs are administered together. [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
PK blood samples will be drawn on Days 1, 7, 14, 21, 28, 35, 42, and at the follow-up visit.
Area under the plasma concentration versus time curve (AUC) of VX-661, VX-770, and their respective metabolites in plasma when VX-661 is administered alone and when the 2 drugs are administered together. [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
PK blood samples will be drawn on Days 1, 7, 14, 21, 28, 35, 42, and at the follow-up visit.
Time to attain maximum plasma concentration (tmax) of VX-661, VX-770, and their respective metabolites in plasma when VX-661 is administered alone and when the 2 drugs are administered together. [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
PK blood samples will be drawn on Days 1, 7, 14, 21, 28, 35, 42, and at the follow-up visit.
Apparent clearance after oral administration (CL/F) of VX-661, VX-770, and their respective metabolites in plasma when VX-661 is administered alone and when the 2 drugs are administered together. [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
PK blood samples will be drawn on Days 1, 7, 14, 21, 28, 35, 42, and at the follow-up visit.
Apparent volume of distribution (V/F) of VX-661, VX-770, and their respective metabolites in plasma when VX-661 is administered alone and when the 2 drugs are administered together. [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
PK blood samples will be drawn on Days 1, 7, 14, 21, 28, 35, 42, and at the follow-up visit.
Apparent terminal elimination half-life (t1/2z) of VX-661, VX-770, and their respective metabolites in plasma when VX-661 is administered alone and when the 2 drugs are administered together. [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
PK blood samples will be drawn on Days 1, 7, 14, 21, 28, 35, 42, and at the follow-up visit.
Accumulation and metabolic ratio of VX-661, VX-770, and their respective metabolites in plasma when VX-661 is administered alone and when the 2 drugs are administered together. [ Time Frame: Through Day 56 ] [ Designated as safety issue: No ]
PK blood samples will be drawn on Days 1, 7, 14, 21, 28, 35, 42, and at the follow-up visit.

Estimated Enrollment:	208
Study Start Date:	February 2012
Estimated Primary Completion Date:	August 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Part A: Monotherapy Subjects randomized to Experimental monotherapy arms will receive different doses of VX-661 monotherapy. Subjects will take VX-661 once daily for 28 days. Some subjects may also receive VX-770 Placebo, which will be taken every 12hr for 28 days.	Drug: VX-661 Tablet, taken once daily (qd) Drug: VX-770 placebo Tablet, taken every 12 hours (q12h)
Experimental: Part A: Co-therapy Subjects randomized to Experimental Co-therapy arms will receive different doses of VX-661 combined with VX-770. The dose of VX-770 will remain the same across all subjects. Subjects randomized to study drug will take VX-661 and VX-770 daily for 28 days.	Drug: VX-661 Tablet, taken once daily (qd) Drug: VX-770 Tablet, taken every 12 hours (q12h) Other Name: ivacaftor
Placebo Comparator: Part A: Placebo Subjects randomized to Placebo arms will receive VX-661 placebo. Some subjects may also receive VX-770 placebo. Subjects will remain on placebo for 28 days. Subjects will be given tablets that match VX-661 and VX-770 and will follow the same dosing regimen as subjects receiving study drug.	Drug: VX-661 placebo Tablet, taken once daily (qd) Drug: VX-770 placebo Tablet, taken every 12 hours (q12h)

Detailed Description:

This is a Phase 2, randomized, multicenter, double-blinded, placebo-controlled, 3-part study of VX 661 monotherapy, VX 770 monotherapy, and VX 661/VX 770 cotherapy in subjects with CF homozygous for the F508del CFTR mutation.

This study will be separated into three parts: Part A, Part B, or Part C. Subjects may only participate in one part of the study. Part A will enroll 120 subjects. Part B will enroll 80 subjects. Part C will enroll 4-8 subjects.

Initiation of Parts B and C will depend on results from PK, PD, and safety data from Part A.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female with confirmed diagnosis of CF
Must have the F508del-CFTR gene mutation in both alleles.
FEV1 40% to 90% (inclusive) of predicted normal for age, gender, and height (Knudson standards)
Subjects of child-bearing and who are sexually active potential 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 subject.
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01531673

Contacts

Contact: Medical Information

617.341.6777

medicalinfo@vrtx.com

Show 37 Study Locations

Sponsors and Collaborators

Vertex Pharmaceuticals Incorporated

Investigators

Principal Investigator:

Scott Donaldson, MD

University of North Carolina

More Information

No publications provided

Responsible Party:	Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:	NCT01531673 History of Changes
Other Study ID Numbers:	VX11-661-101, 2011-003821-93
Study First Received:	February 1, 2012
Last Updated:	May 9, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Cystic Fibrosis
Fibrosis
Pancreatic Diseases
Digestive System Diseases
Lung Diseases

Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on June 17, 2013