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

Abstract

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 mgt.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 FEV(1) 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.