Long-term use of naldemedine in the treatment of opioid-induced constipation in patients with chronic noncancer pain: a randomized, double-blind, placebo-controlled phase 3 study.
Long-term use of naldemedine in the treatment of opioid-induced constipation in patients with chronic noncancer pain: a randomized, double-blind, placebo-controlled phase 3 study.
复制标题
DOI：
10.1097/j.pain.0000000000001174
复制
发表时间：
2018-05
期刊：
影响因子：
7.4
通讯作者：
Arjona Ferreira JC
中科院分区：
文献类型：
--
作者：
Webster LR;Nalamachu S;Morlion B;Reddy J;Baba Y;Yamada T;Arjona Ferreira JC
补充数字内容可在文本中获得。Naldemedine治疗阿片类药物引起的便秘在52周内耐受性良好，没有引起阿片类药物戒断，并且增加了排便和生活质量。naldemedine是一种外周作用的微阿片受体拮抗剂，在一项为期52周的随机、双盲、3期研究中，对阿片诱导的便秘和慢性非癌性疼痛患者使用naldemedine的长期安全性进行了评估。可以接受常规泻药治疗的符合条件的成年人以1:1的比例随机分配，接受每日一次口服0.2 mg的纳尔德美定（n = 623）或安慰剂（n = 623）。主要终点是治疗不良事件（ae）的汇总测量。其他终点分别包括临床阿片类药物戒断量表和主观阿片类药物戒断量表的阿片类药物戒断，数值评定量表的疼痛强度，排便频率，便秘相关症状和生活质量患者便秘症状评估量表和患者便秘生活质量评估量表。相似比例的患者报告了治疗后出现的不良事件（纳地美定，68.4% vs安慰剂，72.1%，差异：- 3.6%[95%可信区间：- 8.7 - 1.5]）和导致研究终止的治疗后出现的不良事件（6.3% vs 5.8%，差异：0.5%[- 2.2 - 3.1）]。与安慰剂（5.3%；差异：5.6%[2.6-8.6]）相比，naldemedine组腹泻发生率更高（11.0%）。两组在阿片类药物戒断或疼痛强度方面无显著差异。在排便频率、总体便秘相关症状和生活质量方面，纳地美定均有持续显著的改善（与安慰剂相比，在所有时间点P≤0.0001）。Naldemedine在52周内耐受性良好，不干扰阿片类药物介导的镇痛或沉淀阿片类药物戒断。与安慰剂相比，纳地美定显著增加了排便频率，改善了阿片类药物引起的便秘的症状负担，并提高了患者的生活质量。
Supplemental Digital Content is Available in the Text. Naldemedine treatment of opioid-induced constipation was well tolerated for 52 weeks, did not precipitate opioid withdrawal, and increased bowel movements and quality of life. The long-term safety of naldemedine, a peripherally acting µ-opioid receptor antagonist, was evaluated in patients with opioid-induced constipation and chronic noncancer pain in a 52-week, randomized, double-blind, phase 3 study. Eligible adults who could be on a routine laxative regimen were randomized 1:1 to receive once-daily oral naldemedine 0.2 mg (n = 623) or placebo (n = 623). The primary endpoint was summary measures of treatment-emergent adverse events (AEs). Additional endpoints included opioid withdrawal on the Clinical Opiate Withdrawal Scale and the Subjective Opiate Withdrawal Scale, pain intensity on Numeric Rating Scale, frequency of bowel movements, and constipation-related symptoms and quality of life on the Patient Assessment of Constipation Symptoms and Patient Assessment of Constipation Quality of Life scales, respectively. Treatment-emergent AEs (naldemedine, 68.4% vs placebo, 72.1%; difference: −3.6% [95% confidence interval: −8.7 to 1.5]) and treatment-emergent AEs leading to study discontinuation (6.3% vs 5.8%; difference: 0.5% [−2.2 to 3.1)] were reported for similar proportions of patients. Diarrhea was reported more frequently with naldemedine (11.0%) vs placebo (5.3%; difference: 5.6% [2.6-8.6]). There were no meaningful differences between groups in opioid withdrawal or pain intensity. Sustained significant improvements in bowel movement frequency and overall constipation-related symptoms and quality of life were observed with naldemedine (P ≤ 0.0001 vs placebo at all time points). Naldemedine was generally well tolerated for 52 weeks and did not interfere with opioid-mediated analgesia or precipitate opioid withdrawal. Naldemedine significantly increased bowel movement frequency, improved symptomatic burden of opioid-induced constipation, and increased patients' quality of life vs placebo.