Conditions: Cystic Fibrosis
Keywords: Fibrosis Pancreatic Diseases Digestive System Diseases Lung Diseases Respiratory Tract Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Pathologic Processes
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 52
Healthy volunteers: no

Brief summary:
The purpose of this study was to evaluate the efficacy and safety of ivacaftor in subjects with cystic fibrosis aged 6 to 11 years who have the G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Ivacaftor is a potent and selective potentiator of wild-type, G551D, F508del, and R117H forms of human CFTR protein. Potentiators are pharmacological agents that increase the chloride ion transport properties of the channel in the presence of cyclic adenosine monophosphate (AMP)-dependent protein kinase A (PKA) activation.

Detailed description:
This is a Phase 3, 2-part, randomized, double-blind, placebo-controlled, parallel group multicenter study of orally administered ivacaftor in subjects with cystic fibrosis (CF) 6 to 11 years of age who have the G551D-CFTR mutation and a forced expiratory volume in 1 second (FEV1) between 90% and 105% predicted (using Knudson standards).

Based on in vitro studies and pharmacologic, pharmacokinetic (PK), and safety profiles, ivacaftor was selected for clinical development as a possible treatment for patients with CF. Patients with the G551D mutation were the targeted population for this study because ivacaftor is a potentiator of the gating effect of the CFTR protein, and the most prevalent mutation with a gating defect in CF is the G551D mutation.

This study was conducted in 2 parts. Part A was conducted to analyze the PK properties of ivacaftor and to determine the most appropriate dose to administer to subjects in Part B of this study. Part B explored the safety and efficacy of ivacaftor over long-term treatment in subjects 6 to 11 years of age.

Arms:
arm 1: Subjects who received placebo every 12 hours (q12h) for up to 48 weeks. arm 2: Subjects who received 150 mg of ivacaftor q12h for up to 48 weeks.

Interventions: intervention 1: Ivacaftor intervention 2: Placebo
Intervention descriptions: intervention 1: 150-mg tablet given orally q12h for up to 48 weeks intervention 2: Tablet given orally q12h for up to 48 weeks

Protocol document: