Relugolix Combination Tablets in Healthy Japanese Premenopausal Women: Pharmacokinetics, Pharmacodynamics, and Safety Profile.

Purpose: To evaluate the applicability of overseas-approved dosage of relugolix combination tablets (relugolix 40 mg, estradiol [E2] 1 mg, and norethisterone acetate 0.5 mg) in healthy premenopausal Japanese women. Methods: A randomized, double-blind phase I/II study was conducted to compare the pharmacokinetics, pharmacodynamics, and safety of repeated once-daily administration of relugolix combination tablets and relugolix (40 mg) for 6 weeks. Results: There were 26 participants in each treatment group. The mean maximum concentration and area under the concentration-time curve from time zero to 24 h ratios for relugolix (relugolix combination tablet group/relugolix group) were both approximately 0.7-0.9. The mean E2 level ranged from 20 to 50 pg/mL. There was no notable difference in luteinizing hormone or follicle-stimulating hormone levels between the two groups. There was less change from baseline in type I collagen C-terminal telopeptide concentration and a lower cumulative incidence of hot flashes in the relugolix combination tablet group compared with the relugolix group, but more participants experienced uterine bleeding (mostly spotting or light bleeding). There were no new safety concerns and relugolix combination tablets were well tolerated. Conclusion: Relugolix combination tablets have favorable safety and efficacy profiles, potentially making them suitable for long-term use in Japanese patients. Trial Registration: The trial registration number is JapicRCT2071230042.