Efficacy and safety of GS1-144, a novel neurokinin 3 receptor antagonist, for moderate-to-severe vasomotor symptoms associated with menopause in Chinese women: a randomized, double-blind, placebo-controlled phase 2 trial
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: OBJECTIVE: This multicenter, randomised, double-blind, placebo-controlled, phase 2 trial investigated the efficacy and safety of the selective neurokinin 3 receptor (NK3R) antagonist GS1-144 for moderate-to-severe vasomotor symptoms (VMS). METHODS: Eligible participants aged between 40 and 64 years randomly (1:1:1:1) received GS1-144 30 mg once daily (QD), 60 mg QD, or 30 mg twice daily (BID) and placebo for 12 weeks. Co-primary endpoints were the mean change in the frequency and severity of moderate-to-severe VMS from baseline to weeks 4 and 12. RESULTS: Among 276 randomized participants, 271 (98.2%) and 258 (93.5%) completed 4 and 12 weeks of treatment, respectively. VMS frequency was significantly reduced versus placebo for GS1-144 30 mg BID at week 4 (difference in change in least squares mean -1.31 [90% CI: -2.35 to -0.26], P =0.04) and week 12 (-1.41 [-2.28 to -0.54], P =0.008), and for GS1-144 60 mg QD at week 12 (-1.42 [-2.28 to 0.55], P =0.007). GS1-144 30 mg BID and 60 mg QD significantly reduced VMS severity versus placebo at week 4 (-0.14 [-0.26 to -0.01], P =0.07; -0.13 [-0.26 to -0.01], P =0.07) and week 12 (-0.24 [-0.43 to -0.05], P =0.04; -0.19 [-0.38 to 0.00], P =0.098). Treatment-emergent adverse events occurred in 67.6% (140/207) of participants who received GS1-144 and 62.3% (43/69) in the placebo group. No liver safety risks were observed with GS1-144. CONCLUSIONS: GS1-144 is well tolerated and significantly reduces VMS frequency and severity in postmenopausal Chinese women.
Institutions: Peking Union Medical College Hospital, Zhujiang Hospital, Southern Medical University, Shanghai First Maternity and Infant Hospital, Fourth Affiliated Hospital of Guangxi Medical University, Shaoxing City Women and Children Hospital, Shanghai Pudong New Area Gongli Hospital, Zhejiang Provincial People's Hospital, Jiangxi Maternal and Child Health Hospital, Central Hospital of Wuhan, Chengdu Women's and Children's Central Hospital, Hunan Provincial Maternal and Child Health Hospital, First Affiliated Hospital of Zhengzhou University, Second Affiliated Hospital of Chongqing Medical University
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7154372344