biostudies-literatureUnknown83(12)Miller BE<h4>Aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Single, oral doses of GSK2793660 were able to dose-dependently inhibit whole blood CTSC activity. Once daily dosing of 12 mg British journal of clinical pharmacology2813-2820https://www.ebi.ac.uk/biostudies/studies/S-EPMC5698569biostudies-literatureEpithelial desquamation observed in a phase I study of an oral cathepsin C inhibitor (GSK2793660).PMC5698569Goyal NMayer RJLazaar ALHeslop TBoyce MBal JCarpenter DMiller BEChurchill ADallow NfalseEpithelial desquamation observed in a phase I study of an oral cathepsin C inhibitor (GSK2793660).<h4>Aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Single, oral doses of GSK2793660 were able to dose-dependently inhibit whole blood CTSC activity. Once daily dosing of 12 mg 2017-01-01T00:00:00Z2017 Dec2026-04-29T07:14:15.502Z2019-03-27T00:09:13ZS-EPMC56985692880038310.1111/bcp.13398