Efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist for vasomotor symptoms: a dose-finding clinical trial (SWITCH-1).
Efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist for vasomotor symptoms: a dose-finding clinical trial (SWITCH-1).
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DOI：
10.1097/gme.0000000000002138
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发表时间：
2023-03-01
影响因子：
2.7
通讯作者：
Pawsey, Steve
中科院分区：
文献类型：
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作者：
Simon, James A.;Anderson, Richard A.;Ballantyne, Elizabeth;Bolognese, James;Caetano, Cecilia;Joffe, Hadine;Kerr, Mary;Panay, Nick;Seitz, Christian;Seymore, Susan;Trower, Mike;Zuurman, Lineke;Pawsey, Steve
elinzanetant-1是一项2b期研究，评估elinzanetant（一种选择性神经激肽-1，3受体拮抗剂）治疗血管紧张症状的疗效、安全性和剂量-反应关系。Elinzanetant可显著改善血管痉挛症状、睡眠和生活质量，并具有临床意义，所有剂量均耐受良好。神经激肽（NK）-3和NK-1受体与绝经期血管紧张症状（VMS）和睡眠障碍的病因有关。这项2b期、适应性、剂量范围探索研究旨在评估多剂量elinzanetant（NT-814）（一种选择性NK-1，3受体拮抗剂）治疗绝经期相关VMS女性的疗效和安全性，并研究elinzanetant对睡眠和生活质量的影响。采用自适应设计算法，将每天发生7次或以上中度至重度VMS的40至65岁绝经后女性随机分配至接受elinzanetant 40、80、120或160 mg或安慰剂，每日1次。共同主要终点为第4周和第12周时中重度VMS的平均频率和严重程度降低。次要终点包括患者报告的睡眠和生活质量评估。从第1周至12周治疗期间，与安慰剂相比，Elinzanetant 120 mg和160 mg实现了VMS频率降低。在两个主要终点时间点，elinzanetant 120 mg组（第4周：− 3.93 [SE，1.02]，P <0.001;第12周：− 2.95 [1.15]，P = 0.01）和elinzanetant 160 mg组（第4周：− 2.63 [1.03]; P = 0.01）的最小二乘均值降低与安慰剂组相比具有统计学显著性。这两种剂量也导致睡眠和生活质量指标的临床有意义的改善。所有剂量的elinzanetant均耐受良好。Elinzanetant是一种有效且耐受性良好的非激素治疗选择，适用于患有VMS和相关睡眠障碍的绝经后妇女。Elinzanetant还可以改善VMS女性的生活质量。
SWITCH-1 was a phase 2b study assessing the efficacy, safety, and dose-response relationship of elinzanetant, a selective neurokinin-1,3 receptor antagonist, for the treatment of vasomotor symptoms. Elinzanetant resulted in significant and clinically meaningful improvements in vasomotor symptoms, sleep and quality of life and was well tolerated across all doses. Neurokinin (NK)-3 and NK-1 receptors have been implicated in the etiology of vasomotor symptoms (VMS) and sleep disturbances associated with menopause. This phase 2b, adaptive, dose-range finding study aimed to assess the efficacy and safety of multiple doses of elinzanetant (NT-814), a selective NK-1,3 receptor antagonist, in women experiencing VMS associated with menopause, and investigate the impact of elinzanetant on sleep and quality of life. Postmenopausal women aged 40 to 65 years who experienced seven or more moderate-to-severe VMS per day were randomized to receive elinzanetant 40, 80, 120, or 160 mg or placebo once daily using an adaptive design algorithm. Coprimary endpoints were reduction in mean frequency and severity of moderate-to-severe VMS at weeks 4 and 12. Secondary endpoints included patient-reported assessments of sleep and quality of life. Elinzanetant 120 mg and 160 mg achieved reductions in VMS frequency versus placebo from week 1 throughout 12 weeks of treatment. Least square mean reductions were statistically significant versus placebo at both primary endpoint time points for elinzanetant 120 mg (week 4: −3.93 [SE, 1.02], P < 0.001; week 12: −2.95 [1.15], P = 0.01) and at week 4 for elinzanetant 160 mg (−2.63 [1.03]; P = 0.01). Both doses also led to clinically meaningful improvements in measures of sleep and quality of life. All doses of elinzanetant were well tolerated. Elinzanetant is an effective and well-tolerated nonhormone treatment option for postmenopausal women with VMS and associated sleep disturbance. Elinzanetant also improves quality of life in women with VMS.