Introduction and objectives Ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, has demonstrated improved outcomes in patients aged ≥6 years with cystic fibrosis (CF) and a CFTR gating mutation. The phase 3, open-label, 24-week KIWI study assessed safety and pharmacokinetics of ivacaftor (50- or 75-mg granules twice daily [bid] for weight.

Methods Patients who completed KIWI could enrol in KLIMB (an 84-week, open-label extension study). Dosing was the same as in KIWI for patients aged <6 years; for patients aged ≥6 years, dosing was 150-mg tablets bid.

Results KIWI enrolled 34 patients (mean age, 3.2 years); 33 enrolled in KLIMB. Cough was the most common AE in both KIWI (56%) and KLIMB (64%). Over the total 72-week treatment period, 8 patients had ALT or AST elevations of >8× the upper limit of normal (ULN), 6 of whom had liver function tests (LFTs) >2× ULN at pretreatment baseline. Six of the 8 patients with LFTs >8× ULN had drug interruption; study drug was subsequently resumed. In total, 3 patients permanently discontinued study drug (elevated LFTs, n = 2; needle phobia, n = 1). Improvements in sweat chloride, faecal elastase-1, and immunoreactive trypsinogen were maintained over 72 weeks. Overall improvements from baseline in other exploratory outcome measures were also observed (Table 1).

Conclusions A favourable overall safety profile was demonstrated with ivacaftor during extended follow-up in preschool patients with CF. Reported adverse events were consistent with the known safety profile of ivacaftor; additional monitoring of liver function may be required in this age group, particularly in patients with a history of elevated LFTs. Improvements in markers of pancreatic function and sweat chloride were sustained over the extended follow-up.