Variation in Sweat Testing Analysis: PTC VISTA

Sweat chloride determinations are used to confirm the diagnosis of CF and also serve as a biomarker for CFTR gene function in clinical trials using protein modulation therapy. Currently, there is uncertainty surrounding the appropriate degree of change in sweat chloride concentrations which reflects a positive response to an investigational drug. Being able to assess a meaningful change is critical to the evaluation of current and future CFTR modulators. The study is a retrospective analysis of repeated sweat chloride tests performed on CF subjects enrolled in placebo arms for clinical drug trials for a nonsense mutation of CFTR. The study data are sweat chloride concentrations from 110 placebo subjects enrolled in PTC Therapeutics Inc. (Planfield NJ) clinical trials evaluating a novel drug, Ataluren. The results from the Ataluren trial will supplement the knowledge gained from the previously funded CF grant, VISTA, which examined biological and analytical variation of sweat chloride concentrations in a drug trial with a different mutation of CFTR. By comparing the results from subjects with 2 different mutations Drs. LeGrys and Moon will be able to determine if variation is similar with differing mutations. This information will be important in assessing whether or not it is reasonable to apply a universal measurement of variation in sweat chloride in clinical drug trials.