Safety and efficacy of ampreloxetine in symptomatic neurogenic orthostatic hypotension: a phase 2 trial.
Safety and efficacy of ampreloxetine in symptomatic neurogenic orthostatic hypotension: a phase 2 trial.
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DOI：
10.1007/s10286-021-00827-0
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Biaggioni I
中科院分区：
文献类型：
--
作者：
Kaufmann H;Vickery R;Wang W;Kanodia J;Shibao CA;Norcliffe-Kaufmann L;Haumann B;Biaggioni I
在神经源性直立性低血压中，由于去甲肾上腺素的释放受损，直立时血压下降，导致头晕。氨丙氯西汀是一种选择性去甲肾上腺素再摄取抑制剂，可增加循环中去甲肾上腺素的水平。本研究探讨氨丙西汀的安全性及其对神经源性直立性低血压患者血压和症状的影响。多中心递增剂量试验(范围1-20 mg，A部分)随后进行为期1天的双盲、随机、安慰剂对照研究(B部分，中位剂量15 mg)。然后，符合条件的患者进入为期20周的开放标签稳定状态扩展阶段(中位剂量10 mg，C部分)，然后停药4周。评估包括直立性低血压症状评定量表(项目1)、仰卧位/坐位/站立血压和安全性。入选患者34例(年龄66 ± 8岁，男性22例)。A部分：服用5毫克和10毫克氨丙西汀的受试者的阳性反应(即 ≥ 10毫米汞柱的静息收缩压较基线有所上升)的比例高于安慰剂或其他活性氨丙西汀剂量。B部分：服用氨丙西汀后4小时坐位血压升高15.7毫米汞柱，服用安慰剂后血压下降14.2毫米汞柱[最小二乘平均差(95%CI)29.9毫米汞柱(7.6-52.3)；P = 0.0112]。C部分：头晕/头晕症状较治疗前改善3.1mmHg± 3.0分，站立收缩压较治疗前升高11 ± 12分。停药4周后，症状恢复到治疗前水平。氨丙西汀在整个治疗过程中对仰卧位血压的影响很小。氨丙西汀耐受性良好，立位症状和坐立血压均有改善，仰卧位血压变化不大。NCT02705755(2016年3月10日首次发布)。
In neurogenic orthostatic hypotension, blood pressure falls when upright owing to impaired release of norepinephrine, leading to dizziness. Ampreloxetine, a selective norepinephrine reuptake inhibitor, increases circulating norepinephrine levels. This study explored the safety of ampreloxetine and its effect on blood pressure and symptoms in patients with neurogenic orthostatic hypotension. A multicenter ascending-dose trial (range 1–20 mg, Part A) was followed by a 1 day, double-blind, randomized, placebo-controlled study (median dose 15 mg, Part B). Eligible patients then enrolled in a 20-week, open-label, steady-state extension phase (median dose 10 mg, Part C) followed by a 4-week withdrawal. Assessments included the Orthostatic Hypotension Symptom Assessment Scale (item 1), supine/seated/standing blood pressure, and safety. Thirty-four patients (age 66 ± 8 years, 22 men) were enrolled. Part A: The proportion of participants with a positive response (i.e., increase from baseline in seated systolic blood pressure of ≥ 10 mmHg) was greater with the 5 and 10 mg ampreloxetine doses than with placebo or other active ampreloxetine doses. Part B: Seated blood pressure increased 15.7 mmHg 4 h after ampreloxetine and decreased 14.2 mmHg after placebo [least squares mean difference (95% CI) 29.9 mmHg (7.6–52.3); P = 0.0112]. Part C: Symptoms of dizziness/lightheadedness improved 3.1 ± 3.0 points from baseline and standing systolic blood pressure increased 11 ± 12 mmHg. After 4 weeks of withdrawal, symptoms returned to pretreatment levels. The effect of ampreloxetine on supine blood pressure was minimal throughout treatment duration. Ampreloxetine was well tolerated and improved orthostatic symptoms and seated/standing blood pressure with little change in supine blood pressure. NCT02705755 (first posted March 10, 2016).
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影响因子：
9.9
作者：
Palma, Jose-Alberto;Norcliffe-Kaufmann, Lucy;Kaufmann, Horatio
通讯作者：
Kaufmann, Horatio
影响因子：
11.2
作者：
Kaufmann H;Norcliffe-Kaufmann L;Palma JA;Biaggioni I;Low PA;Singer W;Goldstein DS;Peltier AC;Shibao CA;Gibbons CH;Freeman R;Robertson D;Autonomic Disorders Consortium
通讯作者：
Autonomic Disorders Consortium
影响因子：
11.2
作者：
Norcliffe-Kaufmann, Lucy;Katz, Stuart D.;Axelrod, Felicia;Kaufmann, Horacio
通讯作者：
Kaufmann, Horacio
影响因子：
11
作者：
HUGHES, AJ;DANIEL, SE;LEES, AJ
通讯作者：
LEES, AJ
影响因子：
5.3
作者：
Byun, Jung-Ick;Kim, Do-Yong;Chu, Kon
通讯作者：
Chu, Kon