PI-064 - EFFECTS OF GLPG3970 ON SULFASALAZINE AND METHOTREXATE PHARMACOKINETICS IN HEALTHY ADULTS: RESULTS OF TWO OPEN-LABEL, PHASE I, DRUG–DRUG INTERACTION STUDIES.
Wednesday, March 22, 2023
5:00 PM – 6:30 PM EDT
M. van der plas1, J. Dao2, V. Zabela2, F. Gistenlinck3, S. Bellaire1; 1Galapagos NV, Leiden, The Netherlands, 2Galapagos SASU, Romainville, France, 3Galapagos NV, Mechelen, Belgium.
Clinical Pharmacology Leader Galapagos SASU, United States
Background: GLPG3970 is a selective salt-inducible kinase 2/3 inhibitor intended for the treatment of inflammatory diseases. In vitro studies indicate GLPG3970 inhibits breast cancer resistance protein (BCRP) transporter, suggesting a possible interaction risk with BCRP substrates e.g. sulfasalazine (SSZ) and methotrexate (MTX), both medications for inflammatory diseases.[1] Methods: Two non-randomized clinical studies (NCT04720183; EudraCT:2020-000391-37) evaluated the pharmacokinetics (PK) of SSZ 1000 mg or MTX 7.5 mg (oral tablets) alone and in combination with GLPG3970 350 mg (oral solution). Healthy adults (18–55 years) received: SSZ on day (D) 1, GLPG3970+SSZ on D5, and GLPG3970 2h after SSZ on D9 (N=8; SSZ study); or MTX on D1, GLPG3970+MTX on D5, and GLPG3970 on D6–8 (N=15; MTX study). Primary endpoints: AUC0-∞ and Cmax of SSZ and its metabolite sulfapyridine (SPD) or MTX; and SPD:SSZ AUC0-∞ ratio. Results: GLPG3970+SSZ increased SSZ exposure (AUC0-∞ and Cmax) ~1.8× and decreased the SPD:SSZ ratio ~2× vs SSZ alone (Table). GLPG3970 taken 2h after SSZ had no PK effect. GLPG3970+MTX had no relevant effect on MTX exposure vs MTX alone. No safety concerns with coadministration. Conclusion: GLPG3970 has a mild inhibitory effect on intestinal BCRP in vivo (SSZ exposure increased ~1.8×) and has no effect on the PK of MTX. GLPG3970+SSZ and GLPG3970+MTX were well tolerated.
[1] FDA. Drug development and drug interactions | table of substrates, inhibitors and inducers. https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers. Accessed September 6, 2022.
Effect of SSZ and GLPG3970 administration on SSZ and SPD PK parameters.
