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

Sep 28, 2026

Uploaded by Margaret

This Phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluated oral zuranolone for 14 days in Japanese adults with major depressive disorder (MDD). Participants aged 18–75 with HAMD-17 total score ≥22 were assigned 1:1 to zuranolone 30 mg once daily or placebo, with follow-up through Day 57. The primary endpoint was HAMD-17 change from baseline at Day 15. Zuranolone showed statistically significant improvement on Day 15 versus placebo, with no serious adverse events reported.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Aim

Methods

Study design

Results

Conclusion

Clinical Trial Registration

Keywords

PCNPsychiatry and Clinical Neurosciences REGULAR ARTICLE Efﬁcacy and safety of zuranolone in Japanese adults with major depressive disorder: A double-blind, randomized, placebo-controlled, Phase 3 clinical trial Masaki Kato, MD, PhD ,1 Kazuyuki Nakagome, MD, PhD ,2 Takamichi Baba, MS,3 Takuhiro Sonoyama, MD, PhD,3 Hiroki Fukuju, MS ,3 Ryosuke Shimizu, PhD,3 Juan Carlos Gomez, MD,4 Tomoko Motomiya, MS 3* and Takeshi Inoue, MD, PhD 5,6 | 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 .
Keywords: depressive disorder, efﬁcacy, Japan, phase 3, zuranolone.
[http://onlinelibrary.wiley.com/doi/10.1111/pcn.13917/full](http://onlinelibrary.wiley.com/doi/10.1111/pcn.13917/full) | | --- | --- | | Major depressive disorder (MDD) is a serious and debilitating illness | oral synthetic neuroactive steroid that displays a similar molecular | | that is also a risk factor for suicide 1, and early treatment intervention | pharmacological proﬁle to the endogenous neuroactive steroid | | is considered important. The estimated global prevalence of MDD in | allopregnanolone 12 and is currently in clinical development in | | 2020 was 2470.5 cases per 100,000 population, and after adjustment | Japan as an oral, once-daily, 14-day treatment course for adults | | for the COVID-19 pandemic, it was 3152.9 cases per 100,000 popu- | with MDD. Zuranolone has been evaluated in several clinical | | lation.2 In Japan, the prevalence of MDD using the Diagnostic and | trials.13–19 The safety and efﬁcacy of zuranolone were assessed in | | Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria was 2 .7% for 12 months and 5 .7% for lifetime.3 | patients with MDD (US [20, 17 30, 16,17 and 50 mg 18 doses]; Japan 19 [20 and 30 mg doses]) . A previous Japanese double-blind, | | While antidepressants are available for treatment of MDD, | Phase 2, placebo-controlled study demonstrated statistically signif- | | their time-to-response can range from weeks to months for | icant improvement in the symptoms of depression in patients with | | some patients,4–8 indicating an unmet need for rapid symptom improvement.9 | MDD on Day 15 after treatment with zuranolone (20 and 30 mg doses) for 2 weeks compared with placebo.19 Thus, the 30 mg | | The gamma-aminobutyric acid (GABA)-A receptor–positive | dose was moved forward for furt

FAQs

What was the primary endpoint of the Phase 3 trial?

The primary endpoint was the change from baseline in the HAMD-17 total score at Day 15.

How was zuranolone administered and for how long?

Participants received oral zuranolone 30 mg once daily for 14 days, compared with placebo.

What safety outcome was reported in the study?

Adverse event frequency was higher with zuranolone (55.1%) than placebo (40.7%), and no serious adverse events were reported.

Sep 28, 2026

Uploaded by Margaret