Effect of GLPG1205, a GPR84 Modulator, on CYP2C9, CYP2C19, and CYP1A2 Enzymes: In Vitro and Phase 1 Studies

Julie Desrivot, Tim Van Kaem, Lisa Allamassey, Eric Helmer, Julie Desrivot, Tim Van Kaem, Lisa Allamassey, Eric Helmer

Abstract

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.

Keywords: GLPG1205; cytochrome P450; drug-drug interaction; idiopathic pulmonary fibrosis.

Conflict of interest statement

T.V.K. and E.H. are employees of Galapagos. J.D. and L.A. are former employees of Galapagos. No COIs were reported by spouses/partners of the authors.

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

Figures

Figure 1
Figure 1
Flow chart to show details of subjects screened, randomized, and allocated to each treatment arm in the DDI study. DDI, drug‐drug interaction.
Figure 2
Figure 2
Effect of concomitant administration of GLPG1205 on plasma concentration‐versus‐time profiles of (A) (S)‐warfarin, (B) omeprazole, and (C) caffeine (mean ± standard error).

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