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

Phase 2

Completed

• Conditions: Cystic Fibrosis
• Interventions: Drug: Ivacaftor; Drug: Placebo

• Registration Number: NCT01262352
• Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary

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.

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.

Study Timeline

• Study First Submitted: 2010-12-15
• Study First Submitted QC: 2010-12-15
• Study First Posted: 2010-12-17
• Study Start: 2011-01
• Primary Completion: 2011-11
• Study Completion: 2011-11
• Results First Submitted: 2012-10-31
• Results First Submitted QC: 2012-12-18
• Results First Posted: 2013-01-30
• Status Verified: 2013-02
• Last Update Submitted: 2013-02-04
• Last Update Posted: 2013-02-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment Sequence 1	Ivacaftor	Ivacaftor administered in Treatment Period 1 and placebo administered in Treatment Period 2.
Treatment Sequence 1	Placebo	Ivacaftor administered in Treatment Period 1 and placebo administered in Treatment Period 2.
Treatment Sequence 2	Ivacaftor	Placebo administered in Treatment Period 1 and ivacaftor administered in Treatment Sequence 2.
Treatment Sequence 2	Placebo	Placebo administered in Treatment Period 1 and ivacaftor administered in Treatment Sequence 2.

Primary Outcome Measures

Name	Time	Method
Absolute Change From Baseline in Lung Clearance Index (LCI)	Baseline through Day 29	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

Name	Time	Method
Absolute Change From Baseline in Percent Predicted FEV1	Baseline through Day 29	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	Baseline through Day 29	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)	Baseline through Day 29	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).