■进行了II期STARLIGHT研究,以调查非唑尼坦在日本女性中的疗效/安全性,并确定未来评估的最佳剂量。
参与者是来自日本36个中心的年龄≥40至≤65岁的围绝经期/绝经后妇女,她们寻求与绝经相关的血管舒缩症状(VMS)的治疗/缓解。筛选后,参与者以1:1:1随机分组,按绝经状态分层,每天一次口服fezolinetant15或30mg或安慰剂,共12周。参与者完成了每日VMS日记。主要终点是从基线到第8周的任何严重程度的VMS频率的平均变化。次要终点包括每周至第12周的VMS频率从基线的平均变化以及不良事件的频率/严重程度。
■共有147名参与者被随机分组(安慰剂,n=47;非唑尼坦15毫克,n=53;非唑林剂30毫克,n=47)。与安慰剂相比,Fezolinetant15和30mg在第8周显示平均VMS频率的统计学显着降低。Fezolinetant15mg的VMS从基线到第8周的平均变化的最小二乘均值估计为-7.04,-6.31用于非唑林坦30mg,安慰剂为-4.55。最小二乘均值估计的差异为-2.50(95%CI:-4.03,-0.96),对于fezolinetant15mg和安慰剂,p=0.002,为-1.76(95%置信区间[CI]:-3.35,-0.17),对于fezolinetant30mg和安慰剂,p=0.030。治疗第1周后,与安慰剂相比,平均VMS频率从基线降低,维持12周。Fezolinetant耐受性良好,没有安全信号的关注任一剂量到第12周。
■每日1次剂量为15或30mg的口服非唑啉对治疗轻度,在这项日本研究中,中度和重度VMS与更年期相关。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: A total of 147 participants were randomized (placebo, n = 47; fezolinetant 15 mg, n = 53; fezolinetant 30 mg, n = 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), p = 0.002 for fezolinetant 15mg and placebo, and was -1.76 (95% confidence interval [CI]: -3.35, -0.17), p = 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.
UNASSIGNED: 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.