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GLPG1205 is a novel agent being investigated for the treatment of idiopathic pulmonary fibrosis. GLPG1205 may be concomitantly administered with pirfenidone in future clinical development; therefore, the potential for GLPG1205 to interact with enzymes involved in the metabolism of pirfenidone (cytochrome P450 [CYP] 1A2, CYP2C9, 2C19) was evaluated. In vitro experiments indicated weak inhibition of CYP1A2 and moderate but reversible inhibition of CYP2C9 and CYP2C19 by GLPG1205. A phase 1 randomized, double-blind crossover study in 14 healthy males (NCT02623296) evaluated the effect of GLPG1205 100 mg or placebo (once daily for 12 days) on the single-dose pharmacokinetics of a cocktail of CYP1A2, CYP2C9, and CYP2C19 substrates (coadministered on day 13). GLPG1205 had no effect on the exposure of CYP2C9 and CYP1A2 substrates or metabolites; however, a trend toward increased omeprazole (CYP2C19 substrate) exposure was observed. Although considered not clinically relevant, GLPG1205 increased the elimination rate of 5-hydroxyomeprazole (CYP2C19 metabolite) 1.16-fold versus placebo. GLPG1205 had no effect on the elimination of all other substrates or metabolites. GLPG1205 had a favorable safety and tolerability profile. In conclusion, GLPG1205 100 mg once daily does not interact with CYP2C9, CYP2C19, or CYP1A2 to a clinically relevant extent and may be administered concomitantly with drugs metabolized by these enzymes., (© 2021 Galápagos NV. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

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., (© 2021 Galápagos NV. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)