S17 Ivacaftor treatment in patients 6 to <12 months old with cystic fibrosis with a CFTR gating mutation: results of a 2-part, single-arm, phase 3 study

Objectives ARRIVAL (NCT02725567) is a single-arm, Phase 3 study of the pharmacokinetics (PK) and safety of ivacaftor (IVA) in patients aged Methods Patients received IVA (5 to Results A and B enrolled 6 and 11 patients; mean age (standard deviation [SD]) was 7.7 (1.9) and 9.0 (1.3) months, respectively. PK from 4 days of IVA dosing in A informed dosing in B, in which exposure was consistent with that observed in adult patients. IVA was generally safe and well tolerated in both parts. In A, one patient had adverse events (AEs) (constipation, vomiting and sleep disorder) considered to be related to study drug. There were no deaths, serious AEs (SAEs) or AEs leading to study drug interruption or discontinuation. In B, one patient had increased alanine aminotransferase (>3 to ≤5 × upper limit of normal) that normalised with continued dosing; three patients reported SAEs (none were deemed related to IVA). Improvements were seen in multiple efficacy endpoints (table 1). Conclusion These results suggest that IVA can be dosed safely in patients aged 6 to Sponsor Vertex Pharmaceuticals Incorporated.