Efficacy and safety of zuranolone in Japanese adults with major depressive disorder: A double-blind, randomized, placebo-controlled, phase 2 clinical trial

Aim: To evaluate the efficacy and safety of an oral, once-daily, 14-day treatment course of zuranolone in Japanese patients with major depressive disorder (MDD).Methods: This multicenter, randomized, double-blind, placebo-controlled study randomized eligible patients (1:1:1) to receive oral zuranolone 20 mg, zuranolone 30 mg, or placebo once daily for 14 days (treatment-period), followed by two 6-week follow-up periods. The primary endpoint was change from baseline in the 17-item Hamilton Depression Rating Scale (HAMD-17) total score on Day 15.Results: Overall, 250 patients (enrolled: 07/07/2020-05/26/2021) were randomized to receive placebo (n = 83), zuranolone 20 mg (n = 85), or zuranolone 30 mg (n = 82). The demographic and baseline characteristics were balanced between groups. The adjusted mean (standard error) change from baseline in the HAMD-17 total score on Day 15 was -6.22 (0.62), -8.14 (0.62), and - 8.31 (0.63) in the placebo, zuranolone 20-mg, and zuranolone 30-mg groups, respectively. Significant differences in the adjusted mean (95% confidence interval [CI]) for zuranolone 20 mg versus placebo (-1.92; [-3.65, -0.19]; P = 0.0296) and zuranolone 30 mg versus placebo (-2.09; [-3.83, -0.35]; P = 0.0190) groups were observed on Day 15, and also as early as Day 3. A nonsignificant yet distinct drug-placebo separation was observed during follow-up. Somnolence (placebo [3.7%], zuranolone 20 mg [10.6%], and zuranolone 30 mg [20.7%]) and dizziness (3.7%, 9.4%, and 9.8%, respectively) were more common with zuranolone.Conclusion: Oral zuranolone was safe and demonstrated significant improvements in depressive symptoms, as assessed by HAMD-17 total score change from baseline over 14 days in Japanese patients with MDD.