The Lancet Respiratory Medicine. 2013, 1 (8).630-638

Phase 2, multicentre, placebo-controlled, double-blind 2×2 crossover study. Randomisation (ratio 1:1) was done with block sizes of 4, and all site personnel including the investigator, the study monitor, and the Vertex study team were masked to treatment assignment.

21 Patients with cystic fibrosis, at least one G551D-CFTR allele, and an FEV1 >90% predicted. Patients also had to have an LCI higher than 7•4 at screening, age of 6 years or older, and a weight higher than or equal to 15 kg.

Patients were randomly allocated to receive one of two treatment sequences (placebo first followed by ivacaftor 150 mg twice daily [sequence 1] or ivacaftor 150 mg twice daily first followed by placebo [sequence 2]) of 28 days' treatment in each period, with a 28-day washout between the two treatment periods.

The primary outcome measure was change from baseline in LCI.

21 patients were enrolled, of which 11 were assigned to the sequence 1 group, and 10 to the sequence 2 group. 20 of these patients received treatment and 17 completed the trial (eight in sequence 1 group and 9 in sequence 2 group). Treatment with ivacaftor led to significant improvements compared with placebo in LCI (difference between groups in the average of mean changes from baseline at days 15 and 29 was −2•16 [95% CI −2•88 to −1•44]; p<0•0001). Adverse events experienced by study participants were similar between treatment groups; at least one adverse event was reported by 15 (79%) of 19 patients who received placebo and 13 (72%) of 18 patients who received ivacaftor. No deaths occurred during study period.

In patients with cystic fibrosis aged 6 years or older who have at least one G551D-CFTR allele, ivacaftor led to improvements in LCI. LCI might be a more sensitive alternative to FEV1 in detecting response to intervention in these patients with mild lung disease.

Screening in cystic fibrosis