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

Study Overview
=================
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.

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

Conditions
-----------------
Cystic Fibrosis

Intervention / Treatment
-----------------
* Drug: Ivacaftor
* Drug: Placebo


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 6 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Sequence 1<br>Ivacaftor administered in Treatment Period 1 and placebo administered in Treatment Period 2. | Drug: Ivacaftor<br>* 150 mg tablet, oral use, twice daily every 12 hours (q12h)<br>Drug: Placebo<br>* Tablet, oral use, twice daily every 12 hours (q12h)<br>|
| Experimental: Treatment Sequence 2<br>Placebo administered in Treatment Period 1 and ivacaftor administered in Treatment Sequence 2. | Drug: Ivacaftor<br>* 150 mg tablet, oral use, twice daily every 12 hours (q12h)<br>Drug: Placebo<br>* Tablet, oral use, twice daily every 12 hours (q12h)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in Lung Clearance Index (LCI) | 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. | Baseline through Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in Percent Predicted FEV1 | Spirometry (as measured by FEV1) is a standardized assessment to evaluate lung function that is the most widely used endpoint in cystic fibrosis studies. | Baseline through Day 29 | 
| Change From Baseline in Sweat Chloride | 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. | Baseline through Day 29 | 
| Change From Baseline in CF Questionnaire-Revised (CFQ-R) Score (Respiratory Domain Score, Pooled) | 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). | Baseline through Day 29 |