First-time-in-Human (FTIH) Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single (in Both Fed and Fasted States) or Repeat Doses of GSK3358699

Summary

This FTIH study, intends to identify the doses of GSK3358699, which are well tolerated by the subjects whilst delivering a robust pharmacodynamic (PD) response. This study will evaluate the safety, tolerability, pharmacokinetic (PK) and PD profile of single (in both fed and fasted states) and multiple ascending doses of GSK3358699 in healthy male subjects within a pre-defined and controlled pharmacodynamic and pharmacokinetic range for each cohort. It also intends to understand the effect of GSK3358699 on systemic markers of inflammation following low dose in vivo lipopolysaccharide (LPS) or Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) challenge and local inflammation in cantharidin-induced blisters. The study has been carefully designed to explore the in vivo biology of the target and the potential for the study drug to become a transformative medicine for subjects in multiple immuno-inflammatory disease indications.

Timeline

Start

2018-03-13

Primary completion

2019-05-02

Completion

2019-05-02

Publications

• Brown JA, Bal J, Simeoni M, Williams P, Mander PK, Soden PE, Daga S, Fahy WA, Wong GK, Bloomer JC, Erwig L, Cui Y, Fernando D, Carnaghan H, Banham-Hall EJ, Hopkins S, Davis BG, Oliveira JJD, Prinjha RK. A randomized study of the safety and pharmacokinetics of GSK3358699, a mononuclear myeloid-targeted bromodomain and extra-terminal domain inhibitor. Br J Clin Pharmacol. 2022 May;88(5):2140-2155. doi: 10.1111/bcp.15137. Epub 2021 Dec 18.

Drugs

Indications