GLPG1205, a GPR84 Modulator: Safety, Pharmacokinetics, and Pharmacodynamics in Healthy Subjects

GLPG1205 is a modulator of GPR84, a G‐protein–coupled receptor reported to be associated with several diseases. Safety, tolerability, pharmacokinetics, and pharmacodynamics of GLPG1205 in healthy subjects were evaluated in 2 randomized, double‐blind, placebo‐controlled, single‐site, phase 1 studies. In study 1, 16 (aged 21‐48 years) and 24 (24‐50 years) healthy men received single doses of GLPG1205 10 to 800 mg, and GLPG1205 50, 100, or 200 mg once daily for 14 days, respectively, or placebo. Study 2 evaluated the effect of aging on GLPG1205 pharmacokinetics: 24 healthy men (aged 37–83 years), weight‐matched into 3 age cohorts (65‐74, ≥75, and 18‐50 years), received GLPG1205 50 mg or placebo once daily for 14 days; an open‐label part of this study evaluated a GLPG1205 250‐mg loading dose followed by 50 mg once daily for 13 days in 8 healthy men (aged 68‐74 years). Single (up to 800 mg) and multiple (maximum tolerated dose 100 mg once daily) GLPG1205 doses had favorable safety and tolerability profiles. After single administration of GLPG1205, median time to occurrence of maximum observed plasma concentration and arithmetic mean apparent terminal half‐life ranged from 2.0 to 4.0 and from 30.1 to 140 hours, respectively. Age did not affect GLPG1205 exposure. GPR84 receptor occupancy with GLPG1205 vs placebo confirmed target engagement. These results support further clinical development of GLPG1205.