Department of Neurology, Dysautonomia Center, NYU Langone Health, New York University School of Medicine, 530 First Avenue, Suite 9Q, New York, NY, 10016, USA.
Theravance Biopharma Ireland Limited, Dublin, Ireland.
Clin Auton Res. 2021 Dec;31(6):699-711. doi: 10.1007/s10286-021-00827-0. Epub 2021 Oct 17.
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).
在神经源性直立性低血压中，由于去甲肾上腺素释放受损，血压在直立时下降，导致头晕。安非他酮是一种选择性去甲肾上腺素再摄取抑制剂，可增加循环去甲肾上腺素水平。本研究探讨了安非他酮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。
一项多中心递增剂量试验（范围 1-20mg，A 部分）后进行了为期 1 天的双盲、随机、安慰剂对照研究（中位数剂量 15mg，B 部分）。符合条件的患者随后参加了 20 周的开放性、稳态扩展阶段（中位数剂量 10mg，C 部分），然后停药 4 周。评估包括直立性低血压症状评估量表（项目 1）、卧位/坐位/站立血压和安全性。
34 名患者（年龄 66±8 岁，22 名男性）入组。A 部分：与安慰剂或其他活性安非他酮剂量相比，5mg 和 10mg 安非他酮剂量的参与者出现阳性反应（即，坐位收缩压从基线升高≥10mmHg）的比例更高。B 部分：安非他酮给药后 4 小时坐位血压升高 15.7mmHg，安慰剂后下降 14.2mmHg[最小二乘均值差值（95%CI）29.9mmHg（7.6-52.3）；P=0.0112]。C 部分：头晕/头晕症状从基线改善 3.1±3.0 分，站立收缩压升高 11±12mmHg。停药 4 周后，症状恢复到治疗前水平。整个治疗过程中，安非他酮对卧位血压的影响很小。
安非他酮耐受性良好，可改善直立性症状和坐位/站立血压，卧位血压变化不大。
NCT02705755（首次发布于 2016 年 3 月 10 日）。
