Efficacy and safety of zuranolone in Japanese adults with major depressive disorder: A double‐blind, randomized, placebo‐controlled, Phase 3 clinical trial

Aim To evaluate the efficacy and safety of oral zuranolone for 14 days, compared with placebo, in Japanese patients with major depressive disorder (MDD). Methods This multicenter, Phase 3 study was conducted in two parts (70 sites; Japan) including a randomized, double‐blind, placebo‐controlled, parallel‐group part presented herein. Participants aged 18–75 years with the 17‐item Hamilton Rating Scale for Depression (HAMD‐17) total score ≥ 22 were randomized (1:1) ratio to receive either zuranolone (30 mg once daily) or placebo for 14 days with follow‐up on Days 3, 8, and 15 and then weekly for 6 weeks (57 days) thereafter. The primary endpoint was change from baseline in the HAMD‐17 total score at Day 15. Results Overall, 412 participants were randomized to receive either zuranolone 30 mg ( n = 207) or placebo ( n = 205). The difference in the least‐squares mean (95% confidence interval [CI]) change from baseline in the HAMD‐17 total score between groups (−1.20; 95% CI: −2.32, −0.08; P = 0.0365) was statistically significant on Day 15. A significant improvement in the HAMD‐17 total score was observed with zuranolone 30 mg during the early treatment period on Days 3 and 8 compared with placebo; however, no significant differences were observed between the groups at later time points, from Day 22 to Day 57. The frequency of adverse events was higher in the zuranolone group (55.1%) than in the placebo group (40.7%); however, no serious adverse events were reported. Conclusion Zuranolone improved depressive symptoms on Day 15, compared with placebo, in Japanese patients with MDD. No new safety signals were observed. Clinical Trial Registration jRCT2031210577.