Epithelial desquamation observed in a phase I study of an oral cathepsin C inhibitor (GSK2793660).

ABSTRACT:

Aims

Cathepsin C (CTSC) is necessary for the activation of several serine proteases including neutrophil elastase (NE), cathepsin G and proteinase 3. GSK2793660 is an oral, irreversible inhibitor of CTSC that is hypothesized to provide an alternative route to achieve NE inhibition and was tested in a Phase I study.

Methods

Single escalating oral doses of GSK2793660 from 0.5 to 20 mg or placebo were administered in a randomized crossover design to healthy male subjects; a separate cohort received once daily doses of 12 mg or placebo for 21 days. Data were collected on safety, pharmacokinetics, CTSC enzyme inhibition and blood biomarkers.

Results

Single, oral doses of GSK2793660 were able to dose-dependently inhibit whole blood CTSC activity. Once daily dosing of 12 mg

SUBMITTER: Miller BE 

PROVIDER: S-EPMC5698569 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature