Safety and efficacy of zuranolone in Japanese adults with major depressive disorder: An open-label, repeated-treatment part of a Phase 3 clinical trial.

Aim: To evaluate the safety and tolerability of repeating 14-day treatment with zuranolone (30 mg) followed by a 6-week follow-up period (one treatment cycle) for a maximum of six treatment cycles in Japanese participants with major depressive disorder. Methods: This multicenter Phase 3 study was conducted in two parts (70 sites; Japan). Part B was an open-label study for participants who completed the initial double-blind study (Part A; zuranolone vs. placebo) in which all eligible participants received zuranolone regardless of their assignments in Part A. Endpoints included treatment-emergent adverse events (TEAEs) and efficacy using the 17-item Hamilton Depression Rating Scale (HAMD-17). Results: A total of 271, 213, 170, 147, 126, and 99 participants were evaluated in Cycles 1-6, respectively. TEAEs occurring in ≥5% of participants were somnolence and dizziness during the treatment period and nasopharyngitis during the follow-up period, and no new safety signals were observed with increased numbers of treatment cycles. Additionally, no TEAEs suggestive of drug dependence or withdrawal symptoms were identified. The HAMD-17 total score decreased by 8 and 15 days after the initiation of zuranolone in all six cycles, and there were no meaningful differences in the HAMD-17 total score reduction across treatment cycles. Conclusion: In this open-label part of the Phase 3 study in Japan, zuranolone decreased the HAMD-17 total scores from baseline over 15 days during repeated treatment cycles in patients with major depressive disorder, without any new safety signals.