A randomized placebo-controlled trial of miglustat in cystic fibrosis based on nasal potential difference

Background: Preclinical data suggest that miglustat could restore the function of the cystic fibrosis transmembrane conductance regulator gene in cystic fibrosis cells. Methods: Single-center, randomized, double-blind, placebo-controlled, crossover Phase II study in 11 patients (mean +/- SD age, 26.3 +/- 7.7 years) homozygous for the F508del mutation received oral miglustat 200 mg t.i.d. or placebo for two 8-day cycles separated by a 14-day washout period. The primary endpoint was the change in total chloride secretion (TCS) assessed by nasal potential difference. Results: No statistically significant changes in TCS, sweat chloride values or FEV1 were detected. Pharmacokinetic and safety were similar to those observed in patients with other diseases exposed to miglustat. Conclusions: There was no evidence of a treatment effect on any nasal potential difference variable. Further studies with miglustat need to adequately address criteria for assessment of nasal potential difference. (C) 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.