Study of VX-809 Alone and in Combination With VX-770 in Cystic Fibrosis (CF) Patients Homozygous or Heterozygous for the F508del-CFTR Mutation - Full Text View

Purpose

The purpose of this study is to evaluate of the safety, efficacy, pharmacokinetics (PK) and pharmacodynamic (PD) effects of VX-809 alone and when coadministered with VX-770. This is the first study to assess the combination of VX-809 and VX-770 in CF subjects homozygous or heterozygous for the F508del-CFTR mutation.

Condition	Intervention	Phase
Cystic Fibrosis	Drug: VX-809 Drug: VX-770 Drug: VX-809 placebo Drug: VX-770 placebo Drug: VX-809 (Cohort 3) Drug: VX-770 (Cohort 3)	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	A Phase 2, Multicenter, Double-Blinded, Placebo-Controlled, Multiple-Dose Study to Evaluate Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-809 Alone and in Combination With VX-770 in Subjects With Cystic Fibrosis, Homozygous or Heterozygous 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:

Change in sweat chloride when VX-770 is administered in combination with VX-809 [ Time Frame: From Day 14 to Day 21 (Cohort 1); Day 28 to Day 56 (Cohort 2 and Cohort 3) ] [ Designated as safety issue: No ]
Safety and Tolerability [ Time Frame: Through Day 35 (Cohort 1); Day 70 (Cohort 2 and Cohort 3) ] [ Designated as safety issue: No ]
Assessments will be measured based on adverse events, plasma samples (hematology, clinical chemistry, coagulation), urinalysis, electrocardiograms, and vital signs

Secondary Outcome Measures:

Change in percent predicted Forced expiratory volume in 1 second (FEV1) [ Time Frame: Through Day 21 (Cohort 1); Day 56 (Cohort 2 and Cohort 3) ] [ Designated as safety issue: No ]
Change in sweat chloride of increasing doses of VX-809 administered alone [ Time Frame: From Baseline to Day 14 (Cohort 1); From baseline to Day 28 (Cohort 2 and Cohort 3) ] [ Designated as safety issue: No ]
PK parameters, including exposure, concentration and half-life, of VX-809 and metabolite in plasma in the presence and absence of VX-770 [ Time Frame: Through Day 21 (Cohort 1); Day 56 (Cohort 2 and Cohort 3) ] [ Designated as safety issue: No ]
Blood samples drawn during the study will be analyzed to measure the PK parameters, such as concentration, exposure and half-life of VX-809 and its metabolite.
PK parameters, including exposure, concentration and half-life, of VX-770 and metabolites in plasma in the presence of VX-809 [ Time Frame: Through Day 21 (Cohort 1); Day 56 (Cohort 2 and Cohort 3) ] [ Designated as safety issue: No ]
Blood samples drawn during the study will be analyzed to measure the PK parameters, such as concentration, exposure and half-life of VX-770 and its metabolites.
Cystic Fibrosis Questionnaire (CFQ-R) Score [ Time Frame: Through Day 56 (Cohort 2 and Cohort 3) ] [ Designated as safety issue: No ]

Estimated Enrollment:	240
Study Start Date:	October 2010
Estimated Study Completion Date:	April 2013
Estimated Primary Completion Date:	April 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Treatment Arm (Cohort 1) Subjects randomized to study drug will take VX-809 once daily for 14 days. Beginning on Day 15, subjects will take both VX-809 and VX-770 through Day 21.	Drug: VX-809 tablet, taken once daily (qd) (Period 1 and 2) Drug: VX-770 tablet, taken every 12 hours (q12h) (Period 2)
Placebo Comparator: Placebo Arm (Cohort 1) Subjects randomized to placebo will remain on placebo from Day 1 through Day 21. Subjects will be given tablets that match both VX-809 and VX-770 and will follow the same dosing regimen as subjects receiving study drug.	Drug: VX-809 placebo tablet, taken once daily (qd) (Period 1 and 2) Drug: VX-770 placebo tablet, taken every 12 hours (q12h) (Period 2) Drug: VX-809 placebo tablet, taken every 12 hours (q12h) or every 8 hours (q8h) (Period 1 and 2) Drug: VX-770 placebo tablet, taken every 12 hours (q12h) or every 8 hours (q8h) (Period 2)
Experimental: Treatment Arm (Cohort 2) Subjects randomized to study drug will take VX-809 once daily for 28 days (Period 1). Beginning on Day 29, subjects will take both VX-809 and VX-770 through Day 56 (Period 2).	Drug: VX-809 tablet, taken once daily (qd) (Period 1 and 2) Drug: VX-770 tablet, taken every 12 hours (q12h) (Period 2)
Placebo Comparator: Placebo Arm (Cohort 2) Subjects randomized to placebo will remain on placebo from Day 1 through Day 56 (Period 1). Subjects will be given tablets that match both VX-809 and VX-770 and will follow the same dosing regimen as subjects receiving study drug (Period 2).	Drug: VX-809 placebo tablet, taken once daily (qd) (Period 1 and 2) Drug: VX-770 placebo tablet, taken every 12 hours (q12h) (Period 2) Drug: VX-809 placebo tablet, taken every 12 hours (q12h) or every 8 hours (q8h) (Period 1 and 2) Drug: VX-770 placebo tablet, taken every 12 hours (q12h) or every 8 hours (q8h) (Period 2)
Experimental: Treatment Arm (Cohort 3) Subjects randomized to study drug will take VX-809 for 28 days (Period 1). Beginning on Day 29, subjects will take both VX-809 and VX-770 through Day 56 (Period 2).	Drug: VX-809 (Cohort 3) tablet, taken every 12 hours (q12h) or every 8 hours (q8h) (Period 1 and 2) Drug: VX-770 (Cohort 3) tablet, taken every 12 hours (q12h) or every 8 hours (q8h) (Period 2)
Placebo Comparator: Placebo Arm (Cohort 3) Subjects randomized to placebo will remain on placebo from Day 1 through Day 56 (Period 1). Subjects will be given tablets that match both VX-809 and VX-770 and will follow the same dosing regiment as subjects receiving study drug (Period 2).	Drug: VX-809 placebo tablet, taken once daily (qd) (Period 1 and 2) Drug: VX-770 placebo tablet, taken every 12 hours (q12h) (Period 2) Drug: VX-809 placebo tablet, taken every 12 hours (q12h) or every 8 hours (q8h) (Period 1 and 2) Drug: VX-770 placebo tablet, taken every 12 hours (q12h) or every 8 hours (q8h) (Period 2)

Detailed Description:

This is a Phase 2, randomized, double-blind, placebo-controlled, multiple-dose study of orally administered VX-809 and VX-770 in CF subjects homozygous or heterozygous for the F508del-CFTR mutation. The primary objectives of the study are to evaluate the safety and tolerability when VX 809 is administered alone and when VX-809 is coadministered with VX-770 and to evaluate the effect of VX-809 administered alone and in combination VX-770 on sweat chloride

Enrollment is planned at clinical sites in the United States, Germany, Belgium, Australia and New Zealand. Up to 240 subjects may be enrolled. The study will be separated into 3 Cohorts. Cohort 1 will enroll 60 subjects. Cohorts 2 will enroll 100 subjects. Cohort 3 evaluating doses higher than Cohort 2, will enroll up to 80 subjects.

Eligibility

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

Criteria

Inclusion Criteria:

Male or female subjects with confirmed diagnosis of CF
Must have the F508del-CFTR mutation on at least 1 allele.
FEV1 >= 40% of predicted normal for age, gender, and height (Knudson standards)
Subjects of child-bearing potential and who are sexually active must meet the contraception requirements

Exclusion Criteria:

History of any illness or condition 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 (e.g., cirrhosis with portal hypertension).
An acute illness including acute upper or lower respiratory infection, pulmonary exacerbation or changes in therapy (including antibiotics) for pulmonary disease within 14 days before receiving the first dose of study drug.
History of solid organ or hematological transplantation.
History of alcohol abuse or drug addiction in the past year, including cannabis, cocaine,and opiates.
Ongoing participation in another therapeutic clinical study, or prior participation in an investigational drug study without appropriate washout
Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of non hormonal contraception
Subjects enrolled in Cohort 1 or Cohort 2 will not be eligible for Cohort 3.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01225211

Hide Study Locations

Locations

United States, Alabama

Birmingham, Alabama, United States
United States, California

Palo Alto, California, United States
United States, Florida

Orlando, Florida, United States
United States, Georgia

Atlanta, Georgia, United States
United States, Illinois

Chicago, Illinois, United States
United States, Kentucky

Lexington, Kentucky, United States
United States, Maryland

Baltimore, Maryland, United States
United States, Massachusetts

Boston, Massachusetts, United States
United States, Minnesota

Minneapolis, Minnesota, United States
United States, New York

Buffalo, New York, United States

Rochester, New York, United States
United States, North Carolina

Chapel Hill, North Carolina, United States
United States, Ohio

Akron, Ohio, United States

Cleveland, Ohio, United States

Columbus, Ohio, United States
United States, South Carolina

Charleston, South Carolina, United States
Australia

Brisbane, Australia

Chermside, Australia

Nedlands, Australia

Parkville, Australia

Perth, Australia

Subiaco, Australia
Belgium

Leuven, Belgium
Germany

Cologne, Germany
New Zealand

Auckland, New Zealand

Christchurch, New Zealand

Sponsors and Collaborators

Vertex Pharmaceuticals Incorporated

Investigators

Study Chair:

Naimish Patel, MD

Vertex Pharmaceuticals Incorporated

More Information

No publications provided

Responsible Party:	Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:	NCT01225211 History of Changes
Other Study ID Numbers:	VX09-809-102, 2010-020413-90
Study First Received:	October 15, 2010
Last Updated:	October 2, 2012
Health Authority:	United States: Food and Drug Administration Australia: Therapeutic Goods Administration Belgium: Federal Agency for Medicinal Products and Health Products Germany: Federal Institute for Drugs and Medical Devices New Zealand: Medsafe

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 13, 2013