Department of Obstetrics and Gynecology, Tokyo Dental College Ichikawa General Hospital, Tokyo, Japan.
Astellas Pharma Inc., Tokyo, Japan.
Climacteric. 2024 Aug;27(4):389-397. doi: 10.1080/13697137.2024.2356854. Epub 2024 Jun 12.
The phase II STARLIGHT study was conducted to investigate the efficacy/safety of fezolinetant in Japanese women and identify the optimal dose for future evaluation.
Participants were perimenopausal/postmenopausal women aged ≥40 to ≤65 years from 36 centers in Japan seeking treatment/relief for vasomotor symptoms (VMS) associated with menopause. After screening, participants were randomized 1:1:1, stratified by menopausal status, to receive fezolinetant 15 or 30 mg or placebo orally once daily for 12 weeks. Participants completed a daily VMS diary. The primary endpoint was mean change in frequency of VMS of any severity from baseline to week 8. Secondary endpoints included mean change in VMS frequency from baseline each week up to week 12 and frequency/severity of adverse events.
A total of 147 participants were randomized (placebo, = 47; fezolinetant 15 mg, = 53; fezolinetant 30 mg, = 47). Fezolinetant 15 and 30 mg demonstrated statistically significant reductions in mean VMS frequency at week 8 versus placebo. Least-squares mean estimates of mean change in frequency of VMS from baseline to week 8 were -7.04 for fezolinetant 15mg, -6.31 for fezolinetant 30mg, and -4.55 for placebo. The difference in least-squares mean estimates was -2.50 (95% CI: -4.03, -0.96), = 0.002 for fezolinetant 15mg and placebo, and was -1.76 (95% confidence interval [CI]: -3.35, -0.17), = 0.030 for fezolinetant 30mg and placebo. Reductions from baseline in mean VMS frequency versus placebo were seen after week 1 of treatment, maintained throughout 12 weeks. Fezolinetant was well tolerated, with no safety signals of concern for either dose to week 12.
Oral fezolinetant at once-daily doses of 15 or 30 mg was efficacious and well tolerated for treatment of mild, moderate and severe VMS associated with menopause in this Japanese study.
STARLIGHT Ⅱ期研究旨在评估 fezolinetant 在日本女性中的疗效/安全性，并确定其未来评估的最佳剂量。
研究纳入 36 家中心的 40 至 65 岁围绝经期/绝经后寻求治疗/缓解与绝经相关血管舒缩症状（VMS）的女性患者。筛选后，根据绝经状态，将患者以 1:1:1 的比例随机分为 fezolinetant 15 或 30mg 或安慰剂组，每日口服一次，疗程 12 周。患者每日填写 VMS 日记。主要终点为治疗第 8 周时任何严重程度 VMS 频率较基线的平均变化。次要终点包括治疗第 1 周至 12 周时每周 VMS 频率的平均变化以及不良事件的频率/严重程度。
共纳入 147 例患者随机分组（安慰剂组，n=47；fezolinetant 15mg 组，n=53；fezolinetant 30mg 组，n=47）。与安慰剂相比，fezolinetant 15 和 30mg 治疗后第 8 周时 VMS 频率的平均降幅均具有统计学意义。治疗第 8 周时 VMS 频率自基线的平均变化最小二乘均数估计值分别为 fezolinetant 15mg 组-7.04，fezolinetant 30mg 组-6.31，安慰剂组-4.55。最小二乘均数估计值的差异分别为-2.50（95%置信区间：-4.03，-0.96），fezolinetant 15mg 与安慰剂相比差异有统计学意义（P=0.002），为-1.76（95%置信区间：-3.35，-0.17），fezolinetant 30mg 与安慰剂相比差异亦有统计学意义（P=0.030）。治疗第 1 周时，与安慰剂相比，fezolinetant 组 VMS 频率即开始降低，且在 12 周内持续下降。Fezolinetant 耐受性良好，至第 12 周时，两种剂量均未出现安全性担忧信号。
在这项日本研究中，每日口服 fezolinetant 15 或 30mg 治疗绝经相关轻、中、重度 VMS 有效且耐受性良好。
