Ivacaftor in cystic fibrosis with residual function: Lung function results from an N-of-1 study

•N-of-1 studies may be useful in studying rare CFTR mutations in patients with CF.•The safety profile of ivacaftor was consistent with that of prior clinical trials.•Ivacaftor is effective in patients with residual-function CFTR mutations. Ivacaftor shows benefit in patients with cystic fibrosis (CF) and CFTR mutations associated with residual CF transmembrane conductance regulator (CFTR) function. Here we further assess the effect of ivacaftor in such patients using an N-of-1 study design. Patients aged ≥12 years with CF with clinical or molecular evidence of residual CFTR function were randomized to 1 of 4 treatment sequences for two 4-week, double-blind crossover cycles (each divided into 2 weeks of ivacaftor treatment and placebo) followed by 8 weeks of open-label ivacaftor treatment. The primary endpoint was absolute change from cycle baseline of percent predicted forced expiratory volume in 1 s (ppFEV1) after 2 weeks of treatment with ivacaftor relative to placebo. Absolute change (SD) from study baseline in ppFEV1 favored ivacaftor by 2.3 (1.0) percentage points (95% credible interval, 0.4–4.1) after 2 weeks of treatment. Absolute mean change (SD) from open-label baseline (defined as day 1 of the open-label ivacaftor treatment period) in ppFEV1 after 8 weeks of treatment was 4.7 (4.2) percentage points (P