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Study of VX-809 in Cystic Fibrosis Subjects With the ∆F508-CFTR Gene Mutation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT00865904
First received: March 18, 2009
Last updated: August 1, 2015
Last verified: June 2015
  Purpose
The primary objective of the study was to evaluate the safety and tolerability of VX-809 in participants with cystic fibrosis (CF) who are homozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene.

Condition Intervention Phase
Cystic Fibrosis
Drug: VX-809
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study of VX-809 to Evaluate Safety, Pharmacokinetics, and Pharmacodynamics of VX-809 in Cystic Fibrosis Subjects Homozygous for the ∆F508-CFTR Gene Mutation

Resource links provided by NLM:


Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • Safety and Tolerability Based on Adverse Events (AEs) [ Time Frame: Up to 14 days after last dose (last dose = Day 28) ] [ Designated as safety issue: Yes ]
    AE: 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) (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Number of participants with AEs and SAEs are reported. An AE that started at or after initial dosing of study drug, or increased in severity after initial dosing of study drug visit is considered treatment-emergent.


Secondary Outcome Measures:
  • Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Day 28 [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

  • Change From Baseline in Percent Predicted FEV1 at Day 28 [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]
    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Predicted FEV1 (for age, gender, and height) was calculated using the Knudson method.

  • Change From Baseline in Forced Vital Capacity (FVC) at Day 28 [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]
    FVC is the volume of air that can be forcibly exhaled from the lungs after taking the deepest breath possible.

  • Change From Baseline in Forced Expiratory Flow Over the Middle Half of the FVC (FEF25-75) at Day 28 [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]
    FEF25-75 is total volume of air exhaled from the lungs over the middle half of the FVC test, expressed as liters per second (L/sec).

  • Change From Baseline in Sweat Chloride at Day 28 [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]
    Sweat samples were collected using an approved Macroduct (Wescor) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride.

  • Change From Baseline in Nasal Potential Difference (NPD) of Zero Chloride Plus Isoproterenol Response at Day 28 [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]

    Nasal potential difference (NPD) provides a direct and sensitive evaluation of sodium and chloride transport in secretory epithelial cells via assessment of transepithelial bioelectric properties. NPD under conditions of zero chloride concentration perfusion solution in the presence of isoproterenol is reported.

    NPDs were performed according to Cystic Fibrosis Foundation Therapeutics Development Network (CFFT TDN) Standard Operating Procedure (SOP) 528.00 "Standardization of Measurement of Nasal Membrane Transepithelial Potential Difference (NPD) - electronic data capture (EDC) and Perfusion or Perfusion-Free Probe".


  • Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Domain Scores at Day 28 [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]
    The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. CFQ-R domains include: Body, Digestion, Eat, Emotion, Health Perceptions, Physical, Respiratory, Role, Social, Treatment Burden, Vitality, and Weight. Individual domain score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

  • Maximum Plasma Concentration (Cmax) of VX-809 [ Time Frame: Day 1 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post-dose), Day 28 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, 24, and 30-60 hours post dose) ] [ Designated as safety issue: No ]
    Only participants who received VX-809 were analyzed for this outcome measure.

  • Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of VX-809 [ Time Frame: Day 1 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post-dose), Day 28 (pre dose, 0.75, 1.5, 3, 4, 6, 9, 12, and 24 hours post dose) ] [ Designated as safety issue: No ]
    Only participants who received VX-809 were analyzed for this outcome measure.


Enrollment: 93
Study Start Date: March 2009
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo matched to VX-809 capsule orally once daily for 28 days.
Drug: Placebo
Placebo matched to VX-809 capsules.
Experimental: VX-809, 25 mg
VX-809, 25 milligram (mg) capsule orally once daily for 28 days.
Drug: VX-809
Capsules
Experimental: VX-809, 50 mg
VX-809, 50 mg capsule orally once daily for 28 days.
Drug: VX-809
Capsules
Experimental: VX-809, 100 mg
VX-809, 100 mg capsule orally once daily for 28 days.
Drug: VX-809
Capsules
Experimental: VX-809, 200 mg
VX-809, 200 mg capsule orally once daily for 28 days.
Drug: VX-809
Capsules

Detailed Description:
This was a Phase 2, randomized, double-blind, placebo-controlled, multiple-dose study of orally-administered VX-809 in participants with CF who are homozygous for the specific CFTR mutation known as ∆F508 or F508del. Enrollment was planned for 90 participants at approximately 20 centers. Participants were planned to be randomized in a 4:1 ratio to receive 1 of 4 doses of VX-809 or placebo once a day for 28 days in a parallel design. Participants were outpatients during the study, except for overnight stays on Day 1 and 28.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of CF with ∆F508-CFTR mutation in both alleles
  • Forced expiratory volume in 1 second (FEV1) greater than or equal to (>=) 40 percent (%) of predicted normal for age, gender, and height
  • Weight >=40 kilograms (kg) and body mass index greater than or equal to 18.5 kilogram per square meter (kg/m^2)
  • Screening laboratory values, tests, and physical examination within acceptable ranges
  • Negative pregnancy test (for women of child-bearing potential)
  • Able and willing to follow contraceptive requirements
  • Willing to remain on a stable medication regimen for the duration of study participation

Exclusion Criteria:

  • History of any illness, or any ongoing acute illness, that could impact the safety of the study participant or may confound results of study
  • Pulmonary exacerbation or changes in therapy for pulmonary disease within 14 days before receiving the first dose of study drug
  • Impaired hepatic or renal function
  • History of organ or hematological transplant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00865904

  Show 25 Study Locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Investigators
Study Director: Medical Monitor Vertex Pharmaceuticals Incorporated
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT00865904     History of Changes
Other Study ID Numbers: VX08-809-101 
Study First Received: March 18, 2009
Results First Received: August 1, 2015
Last Updated: August 1, 2015
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Germany: Federal Institute for Drugs and Medical Devices
Belgium: Federal Agency for Medicinal Products and Health Products
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Vertex Pharmaceuticals Incorporated:
∆F508
F508del
Cystic Fibrosis Transmembrane Conductance Regulator
CFTR
Pancreatic diseases
Lung diseases
Genetic disease, inborn
Infant, newborn, diseases

Additional relevant MeSH terms:
Fibrosis
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases

ClinicalTrials.gov processed this record on December 02, 2016