Upstate Clinical Research Associates, 8201 Main Street, Suite 1, Williamsville, NY, 14221, USA.
PRA Health Sciences, Salt Lake City, UT, USA.
Drugs Aging. 2020 Apr;37(4):271-279. doi: 10.1007/s40266-020-00753-2.
Opioid-induced constipation (OIC), the most common side effect of opioid treatment, is under-recognized and undertreated in older patients. Naldemedine, an oral, peripherally acting μ-opioid receptor antagonist (PAMORA), is approved in Japan, the United States, and the European Union for treatment of OIC in adult patients.
This integrated analysis of three phase 3 trials (COMPOSE-1, COMPOSE-2, and COMPOSE-3) evaluated the safety and efficacy of naldemedine for up to 12 weeks in a subgroup of patients aged ≥ 65 years.
Patients aged 18-80 years with chronic non-cancer pain for ≥ 3 months (treated with opioids for ≥ 3 months in COMPOSE-1 and COMPOSE-2) and OIC received oral naldemedine 0.2 mg or placebo once daily. Safety assessments included overall incidence of treatment-emergent adverse events (TEAEs), TEAEs in the gastrointestinal disorders System Organ Class, and TEAEs of opioid withdrawal or possible opioid withdrawal. Efficacy was based on the proportion of responders in COMPOSE-1 and COMPOSE-2, defined as having ≥ 3 spontaneous bowel movements/week and a ≥ 1-spontaneous bowel movement/week increase from baseline for ≥ 9 of 12 weeks and ≥ 3 of the last 4 weeks.
A total of 14.8% (344/2328) of patients were aged ≥ 65 years in all studies. The incidence of TEAEs in naldemedine-treated patients aged ≥ 65 years (45.9%) was comparable to that in patients aged ≥ 65 years receiving placebo (51.6%) and in the overall naldemedine group (47.1%). The incidence of gastrointestinal disorders System Organ Class TEAEs in naldemedine-treated patients aged ≥ 65 years (20.2%) was also comparable to that in patients aged ≥ 65 years receiving placebo (16.1%) and in the overall naldemedine group (21.8%). The incidence of TEAEs of opioid withdrawal with naldemedine was 1.1% in patients aged ≥ 65 years and 1.0% overall, and the incidence of TEAEs of possible opioid withdrawal was 1.1% in patients aged ≥ 65 years and 1.7% overall. The proportion of responders was higher in naldemedine-treated patients versus placebo, both overall (50.1% vs 34.1%; p < 0.0001) and in those aged ≥ 65 years (51.8% vs 37.6%).
This integrated analysis confirmed that OIC treatment with naldemedine 0.2 mg was generally well tolerated and effective in patients aged ≥ 65 years with chronic non-cancer pain. Safety and efficacy results were consistent with the overall patient population. CLINICALTRIALS.
NCT01965158, NCT01993940, NCT01965652.
阿片类药物诱导的便秘（OIC）是阿片类药物治疗中最常见的副作用，但在老年患者中往往未被充分认识和治疗。纳洛美丁是一种口服、外周作用μ-阿片受体拮抗剂（PAMORA），已在日本、美国和欧盟获批用于治疗成年患者的 OIC。
这项对三项 3 期临床试验（COMPOSE-1、COMPOSE-2 和 COMPOSE-3）的综合分析评估了纳洛美丁在年龄≥65 岁患者亚组中最长 12 周的安全性和疗效。
年龄 18-80 岁、慢性非癌痛≥3 个月（在 COMPOSE-1 和 COMPOSE-2 中接受阿片类药物治疗≥3 个月）且患有 OIC 的患者接受纳洛美丁 0.2mg 或安慰剂每日一次口服治疗。安全性评估包括治疗期间出现的不良事件（TEAE）的总发生率、胃肠道疾病系统器官类别中的 TEAEs 以及阿片类药物戒断或可能的阿片类药物戒断的 TEAEs。疗效基于 COMPOSE-1 和 COMPOSE-2 中的应答者比例，定义为≥3 次自发排便/周且与基线相比每周至少增加 1 次自发排便，持续 12 周中的≥9 周和最后 4 周中的≥3 周。
所有研究中共有 14.8%（344/2328）的患者年龄≥65 岁。纳洛美丁治疗的年龄≥65 岁患者（45.9%）的 TEAEs 发生率与安慰剂组（51.6%）和纳洛美丁总体组（47.1%）相似。纳洛美丁治疗的年龄≥65 岁患者中胃肠道疾病系统器官类别 TEAEs 的发生率（20.2%）与安慰剂组（16.1%）和纳洛美丁总体组（21.8%）相似。纳洛美丁治疗的年龄≥65 岁患者的阿片类药物戒断 TEAEs 发生率为 1.1%，总体发生率为 1.0%，阿片类药物可能戒断的 TEAEs 发生率为 1.1%，总体发生率为 1.7%。纳洛美丁治疗的患者与安慰剂组相比，总体应答者比例更高（50.1%比 34.1%；p<0.0001），年龄≥65 岁的患者也更高（51.8%比 37.6%）。
这项综合分析证实，纳洛美丁 0.2mg 治疗 OIC 在慢性非癌痛的老年患者中通常具有良好的耐受性和疗效。安全性和疗效结果与总体患者人群一致。临床试验注册：NCT01965158、NCT01993940、NCT01965652。
