Efficacy and safety of zuranolone in Japanese adults with major depressive disorder: A double‐blind, randomized, placebo‐controlled, phase 2 clinical trial
Masaki Kato, Kazuyuki Nakagome, Takamichi Baba, Takuhiro Sonoyama, Daiki Okutsu, Hideki Yamanaka, Ryosuke Shimizu, Tomoko Motomiya, Takeshi Inoue
Abstract
[Corrections added on 20 December 2024, after first online publication: The Results section in the Abstract has been revised to report on updated data following the re‐analysis of the study results using revised numbers of patients in the three groups ‐ zuranolone 20 mg [N=84], zuranolone 30 mg [N=79], and placebo [N=79] ‐ that were included in the full analyses set and the safety analysis set.] 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, of whom 79 in the placebo group, 84 in the zuranolone 20‐mg group, and 79 in the zuranolone 30‐mg group were included in the full analysis set (FAS) population. 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 −6.09 (0.64), −8.18 (0.63), and − 8.33 (0.65) in the placebo, zuranolone 20‐mg, and zuranolone 30‐mg groups, respectively. Significant differences in the adjusted mean (95% confidence interval [CI]) for the zuranolone 20‐mg versus placebo (−2.09; [−3.86, −0.33]; P = 0.0204) and zuranolone 30‐mg versus placebo (−2.24; [−4.03, −0.45]; P = 0.0146) groups were observed on Day 15, and also as early as Day 3 for zuranolone 30 mg. A nonsignificant yet distinct drug‐placebo separation was observed in the zuranolone 30‐mg group during follow‐up. Somnolence (placebo [3.8%], zuranolone 20 mg [10.7%], and zuranolone 30 mg [21.5%]) and dizziness (2.5%, 9.5%, and 8.9%, respectively) were more common drug reactions in the treatment period with zuranolone. Conclusion Oral zuranolone was safe and demonstrated significant improvements in depressive symptoms, as assessed by the HAMD‐17 total score change from baseline over 14 days in Japanese patients with MDD.