iResearch Atlanta, LLC, Decatur, Georgia 30030, USA.
Employee of Astellas Pharma Global Development at the Time of the Study, Northbrook, IL, USA.
J Clin Endocrinol Metab. 2023 Jul 14;108(8):1981-1997. doi: 10.1210/clinem/dgad058.
Vasomotor symptoms (VMS) are common, bothersome, and can persist for years before and after menopause.
We aimed to assess efficacy/safety of fezolinetant for treatment of moderate to severe VMS associated with menopause.
In this double-blind, placebo-controlled, 12-week phase 3 trial with a 40-week active treatment extension (NCT04003142; SKYLIGHT 2), women aged 40 to 65 years with minimum average 7 moderate to severe VMS/day were randomized to 12 weeks of once-daily placebo, fezolinetant 30 mg, or fezolinetant 45 mg. Completers were rerandomized to fezolinetant 30/45 mg for 40 additional weeks. Coprimary efficacy endpoints were mean daily change from baseline to week 4 (W4) and W12 in VMS frequency and severity. Safety was also assessed.
Both fezolinetant doses statistically significantly reduced VMS frequency/severity at W4 and W12 vs placebo. For VMS frequency, W4 least squares mean (SE) reduction vs placebo: fezolinetant 30 mg, -1.82 (0.46; P < .001); 45 mg, -2.55 (0.46; P < .001); W12: 30 mg, -1.86 (0.55; P < .001); 45 mg, -2.53 (0.55; P < .001). For VMS severity, W4: 30 mg, -0.15 (0.06; P < .05); 45 mg, -0.29 (0.06; P < .001); W12: 30 mg, -0.16 (0.08; P < .05); 45 mg, -0.29 (0.08; P < .001). Improvement in VMS frequency and severity was observed by W1 and maintained through W52. Serious treatment-emergent adverse events were infrequent, reported by 2%, 1%, and 0% of those receiving fezolinetant 30 mg, fezolinetant 45 mg, and placebo, respectively.
Daily fezolinetant 30 and 45 mg were efficacious and well tolerated for treating moderate to severe VMS associated with menopause.
血管舒缩症状（VMS）很常见，令人困扰，并且在绝经前后可能持续多年。
我们旨在评估 fezolinetant 治疗与绝经相关的中度至重度 VMS 的疗效/安全性。
在这项双盲、安慰剂对照、为期 12 周的 3 期临床试验中，有 40 周的活性治疗扩展期（NCT04003142；SKYLIGHT 2），年龄在 40 至 65 岁之间、平均每天至少有 7 次中度至重度 VMS 的女性随机分配接受为期 12 周的每日一次安慰剂、fezolinetant 30mg 或 fezolinetant 45mg。完成者被重新随机分配接受 fezolinetant 30/45mg 治疗 40 周。主要疗效终点是从基线到第 4 周（W4）和第 12 周（W12）VMS 频率和严重程度的平均每日变化。还评估了安全性。
两种剂量的 fezolinetant 均在 W4 和 W12 时显著降低 VMS 频率/严重程度与安慰剂相比。对于 VMS 频率，W4 最小二乘均值（SE）与安慰剂相比的降低：fezolinetant 30mg，-1.82（0.46；P<.001）；45mg，-2.55（0.46；P<.001）；W12：30mg，-1.86（0.55；P<.001）；45mg，-2.53（0.55；P<.001）。对于 VMS 严重程度，W4：30mg，-0.15（0.06；P<.05）；45mg，-0.29（0.06；P<.001）；W12：30mg，-0.16（0.08；P<.05）；45mg，-0.29（0.08；P<.001）。从第 1 天开始观察到 VMS 频率和严重程度的改善，并在第 52 周时保持不变。严重的治疗相关不良事件很少见，分别有 2%、1%和 0%接受 fezolinetant 30mg、fezolinetant 45mg 和安慰剂治疗的患者报告。
每日 fezolinetant 30mg 和 45mg 治疗与绝经相关的中度至重度 VMS 有效且耐受良好。
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