Study of the Effect of Ivacaftor on Lung Clearance Index in Subjects With Cystic Fibrosis and the G551D Mutation

This study has been completed.
Sponsor:
Collaborator:
Cystic Fibrosis Foundation
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT01262352
First received: December 15, 2010
Last updated: February 4, 2013
Last verified: February 2013
  Purpose

The purpose of this study is to evaluate the effect of ivacaftor (VX-770) on lung clearance index (LCI) in subjects aged 6 years and older with cystic fibrosis (CF) who have the G551D-CFTR mutation on at least 1 allele.


Condition Intervention Phase
Cystic Fibrosis
Drug: Ivacaftor
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Effect of VX-770 on Lung Clearance Index in Subjects With Cystic Fibrosis, the G551D Mutation, and FEV1 >90% Predicted

Resource links provided by NLM:


Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • Absolute Change From Baseline in Lung Clearance Index (LCI) [ Time Frame: Baseline through Day 29 ] [ Designated as safety issue: No ]
    Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal SF6 concentration to 1/40th of the starting value.


Secondary Outcome Measures:
  • Absolute Change From Baseline in Percent Predicted FEV1 [ Time Frame: Baseline through Day 29 ] [ Designated as safety issue: No ]
    Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies.

  • Change From Baseline in Sweat Chloride [ Time Frame: Baseline through Day 29 ] [ Designated as safety issue: No ]
    The sweat chloride (quantitative pilocarpine iontophoresis) test is a standard diagnostic tool for cystic fibrosis (CF), serving as an indicator of cystic fibrosis transmembrane conductance regulator (CFTR) activity.

  • Change From Baseline in CF Questionnaire-Revised (CFQ-R) Score (Respiratory Domain Score, Pooled) [ Time Frame: Baseline through Day 29 ] [ Designated as safety issue: No ]
    The CFQ-R is a health-related quality of life measure for subjects with cystic fibrosis. Each domain is scored from 0 (worst) to 100 (best). A difference of at least 4 points in the respiratory domain score of the CFQ-R is considered a minimal clinically important difference (MCID). The primary analytical focus was the respiratory health domain, which was analyzed by combining all self-response questionnaire versions from different age groups (e.g., Adult/Adolescent and Child versions).


Enrollment: 21
Study Start Date: January 2011
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Sequence 1
Ivacaftor administered in Treatment Period 1 and placebo administered in Treatment Period 2.
Drug: Ivacaftor
150 mg tablet, oral use, twice daily every 12 hours (q12h)
Drug: Placebo
Tablet, oral use, twice daily every 12 hours (q12h)
Experimental: Treatment Sequence 2
Placebo administered in Treatment Period 1 and ivacaftor administered in Treatment Sequence 2.
Drug: Ivacaftor
150 mg tablet, oral use, twice daily every 12 hours (q12h)
Drug: Placebo
Tablet, oral use, twice daily every 12 hours (q12h)

Detailed Description:

Currently, limited objective measures are available to quantify lung function in CF patients with mild lung disease. Lung clearance index (LCI) derived from inert gas multiple-breath washout (MBW) testing hold considerable promise to evaluate early lung disease as studies have detected abnormalities in a high percentage of CF patients with normal spirometry in both infants and children.

This study explored the effect of ivacaftor on LCI and the efficacy of ivacaftor on other clinical and biomarker endpoints of CF lung disease in subjects aged 6 years and older with CF who have the G551D-CFTR mutation on at least 1 allele.

  Eligibility

Ages Eligible for Study:   6 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 G551D-CFTR mutation in at least 1 allele
  • FEV1 >90% of predicted normal for age, gender, and height

Exclusion Criteria:

  • Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within the 30 days prior to screening
  • Use of inhaled hypertonic saline treatment within 2 weeks of the Period 1, Day 1 visit
  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: NCT01262352

Locations
United States, California
Stanford, California, United States
United States, Iowa
Iowa City, Iowa, United States
United States, North Carolina
Durham, North Carolina, United States
United States, Pennsylvania
Pittsburgh, Pennsylvania, United States
Canada, Ontario
Toronto, Ontario, Canada
United Kingdom
Belfast, United Kingdom
Edinburgh, United Kingdom
London, United Kingdom
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Cystic Fibrosis Foundation
Investigators
Principal Investigator: Jane Davies Royal Brompton Hospital and Imperial College
Principal Investigator: Felix Ratjen The Hospital for Sick Children
  More Information

No publications provided by Vertex Pharmaceuticals Incorporated

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01262352     History of Changes
Other Study ID Numbers: VX10-770-106
Study First Received: December 15, 2010
Results First Received: October 31, 2012
Last Updated: February 4, 2013
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Canada: Health Canada

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 August 21, 2014