A phase 2, multicenter, double-blind, placebo-controlled, multiple-dose study to evaluate safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of lumacaftor alone and in combination with ivacaftor in subjects with cystic fibrosis, homozygous or heterozygous for the F508del-CFTR mutation
This phase 2 trial (NCT01225211) was conducted in 24 sites in 5 countries (Australia, Belgium, Germany, New Zealand and the USA) to evaluate safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of lumacaftor alone and in combination with ivacaftor in subjects with cystic fibrosis, homozygous or heterozygous for the F508del-CFTR mutation. Three cohorts of CF patients (≥ 18 years-old) homozygous or heterozygous for the F508del-CFTR mutation were enrolled in a double-blind, placebo-controlled, multiple-dose study to receive lumacaftor (200, 400 or 600 mg once a day) for 14 or 28 days followed by addition of ivacaftor (150 or 250 mg q12h) for 14 or 28 days, or placebo for 21 or 56 days. The results showed that in patients homozygous for the F508del-CFTR mutation, the lumacaftor 600 mg once per day significantly improved FEV1 from day 1 to 56 (difference compared with placebo group: +5.6 percentage points, p=0.013), primarily during the combination period. In some cohorts, mean sweat chloride concentrations decreased significantly but never more than by 10.3 mmol/L. In patients heterozygous for the F508del-CFTR mutation, there was no significant improvement in FEV1. Frequency and nature of adverse events were similar in the treatment and placebo groups during the combination treatment period. In conclusion, combination of lumacaftor and ivacaftor improves FEV1 for patients with cystic fibrosis who are homozygous for the F508del-CFTR, with a modest effect on sweat chloride concentration.
2 ECFS-CTN sites in Belgium and Germany participated in this study and enrolled 12 of the patients.
The summary of data provided here are from the article published in the Lancet Respir Med 2014; 2:527-38.