WS01.5 An open-label study of the safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2 to 5 years with cystic fibrosis and a CFTR gating mutation: The KIWI study

Abstract

Background Ivacaftor potentiates CFTR chloride transport and improves outcomes in patients ≥6 y with CF and a CFTR gating mutation. This 2-part study evaluated ivacaftor in patients aged 2–5 y with CF and a gating mutation. Methods In Part A, patients received ivacaftor (50 or 75 mg granules q12h for weight Results Part A enrolled 9 and Part B 34 patients (mean age 3.2 y). Ivacaftor exposure in Parts A and B was similar to that of adults in other studies. In Part A, the most common AE was pyrexia (44%); in Part B, cough (56%). Five patients (14.7%) experienced elevations in ALT or AST of >8×ULN, all of whom had liver function tests (LFTs) >2×ULN at study baseline and returned to baseline following interruption. At Week 24, significant mean (±SD) changes were seen in sweat chloride (–46.9±26.2 mmol/L; P Conclusion Ivacaftor 50 and 75 mg q12h regimens are appropriate for children aged 2–5 y. Improvements in sweat chloride, nutrition status, and pancreatic function were observed over 24 weeks. The majority of AEs seen were mild to moderate in severity. Elevations in ALT or AST were noted in some patients with abnormal baseline LFTs.