Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT.
Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT.
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DOI：
10.1210/clinem/dgad058
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发表时间：
2023-07-14
影响因子：
5.8
通讯作者：
Santoro, Nanette
中科院分区：
文献类型：
--
作者：
Johnson, Kimball A.;Martin, Nancy;Nappi, Rossella E.;Neal-Perry, Genevieve;Shapiro, Marla;Stute, Petra;Thurston, Rebecca C.;Wolfman, Wendy;English, Marci;Franklin, Catherine;Lee, Misun;Santoro, Nanette
血管运动症状(VMS)是常见的、令人烦恼的，可以在绝经前后持续数年。我们的目标是评估非唑林奈特治疗与绝经相关的中到重度VMS的有效性/安全性。在这项为期12周的双盲、安慰剂对照、为期12周的第三阶段试验中，年龄在40岁到65岁之间、平均每天至少有7例中度到重度VMS的妇女被随机分成三组，每天服用一次安慰剂、30毫克或45毫克的非唑林奈特。补充者被重新随机给予苯唑仑30/45 mg，持续40周。主要疗效终点是从基线到第4周(W4)和W12的VMS频率和严重程度的平均日变化。安全性也进行了评估。与安慰剂相比，在W4和W12，两种剂量的苯唑仑都显著降低了VMS的频率/严重程度。对于VMS频率，与安慰剂相比，W4最小二乘平均(SE)减少：苯唑林特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)。对于VMS严重程度，W4：30 mg，−0.15(0.06；P<；0.05)；45 mg，−0.29(0.06；P<；.001)；W12：30 mg，−0.16(0.08；P<；0.05)；45 mg，−0.29(0.08；P<；.001)。W1观察到VMS频率和严重程度的改善，并持续到W52。严重的治疗-紧急不良事件很少见，分别报告了服用30毫克、45毫克和安慰剂的患者中2%、1%和0%的不良反应。每日服用苯唑仑30 mg和45 mg对治疗与绝经相关的中重度VMS有效且耐受性良好。
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.
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影响因子：
12.7
作者：
Gold, Ellen B.;Colvin, Alicia;Matthews, Karen
通讯作者：
Matthews, Karen
影响因子：
3.3
作者：
Freeman EW;Ensrud KE;Larson JC;Guthrie KA;Carpenter JS;Joffe H;Newton KM;Sternfeld B;LaCroix AZ
通讯作者：
LaCroix AZ
影响因子：
2.7
作者：
English M;Stoykova B;Slota C;Doward L;Siddiqui E;Crawford R;DiBenedetti D
通讯作者：
DiBenedetti D
影响因子：
7.4
作者：
Rance, Naomi E.;Dacks, Penny A.;Mittelman-Smith, Melinda A.;Romanovsky, Andrej A.;Krajewski-Hall, Sally J.
通讯作者：
Krajewski-Hall, Sally J.
影响因子：
39
作者：
Avis, Nancy E.;Crawford, Sybil L.;Greendale, Gail;Bromberger, Joyce T.;Everson-Rose, Susan A.;Gold, Ellen B.;Hess, Rachel;Joffe, Hadine;Kravitz, Howard M.;Tepper, Ping G.;Thurston, Rebecca C.
通讯作者：
Thurston, Rebecca C.