在一项新型镇痛药 NKTR-181（羟考酮醇）治疗中重度慢性下腰痛的 3 期研究中测量阿片类药物戒断。

Measuring Opioid Withdrawal in a Phase 3 Study of a New Analgesic, NKTR-181 (Oxycodegol), in Patients with Moderate to Severe Chronic Low Back Pain.

机构信息

Pinney Associates, Bethesda, Maryland.

Englewood Hospital and Medical Center, Englewood, New Jersey.

出版信息

Pain Med. 2020 Aug 1;21(8):1553-1561. doi: 10.1093/pm/pnz326.

DOI:10.1093/pm/pnz326

PMID:32150255

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7530570/

Abstract

OBJECTIVE

To evaluate the SUMMIT-07 trial opioid withdrawal results of NKTR-181 (oxycodegol), a new molecular entity mu-opioid receptor agonist.

DESIGN

Phase 3, enriched-enrollment, double-blind, randomized-withdrawal study in patients with chronic low back pain (CLBP).

SETTING

Conducted in the United States at multiple sites.

METHODS

SUMMIT-07 was comprised of five periods: screening; NKTR-181 open-label titration (100 to 400 mg twice daily); 12-week randomized, double-blind study drug (NKTR-181 or placebo); one-week study drug taper; and two-week safety follow-up. Permitted rescue medication included hydrocodone 5 mg/acetaminophen 300 mg (two tablets daily) for two weeks after randomization, then acetaminophen 1.0 gm daily for the remainder of the trial. Signs and symptoms of drug withdrawal were evaluated using the Clinical Opiate Withdrawal Scale (COWS); Subjective Opiate Withdrawal Scale (SOWS); Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS); and withdrawal-related adverse events.

RESULTS

Of 1,190 patients entering titration, one patient had moderate withdrawal (COWS score 13/48 maximum) three days after discontinuing NKTR-181. Of 610 patients randomized (N = 309, NKTR-181; N = 301, placebo), no COWS scores indicating withdrawal at a moderate level or greater (i.e., score ≥13) were observed at any time point. At day 8 after randomization, week 12, and the end of tapering, COWS scores indicating mild withdrawal (<13) were observed in seven (2.4%), one (0.4%), and one (0.5%) placebo patients, respectively, and three (1.0%), one (0.4%), and five (2.3%) NKTR-181 patients, respectively. Mean SOWS scores in both arms were ≤2.8 of 64 possible points at all time points. During the randomized period, of 35 events identified by MADDERS, adjudicators identified 20 possible "withdrawal" events (9 [2.9%] NKTR-181 and 11 [3.7%] placebo).

CONCLUSIONS

NKTR-181 exhibited a low rate and severity of opioid withdrawal in SUMMIT-07 patients with CLBP.

摘要

目的

评估 SUMMIT-07 试验中新型阿片受体激动剂 NKTR-181（氧可酮醇）的阿片类药物戒断结果。

设计

一项在慢性下背痛（CLBP）患者中进行的、有富集入组人群的、双盲、随机撤药的 3 期研究。

设置

在美国多个地点进行。

方法

SUMMIT-07 由五个阶段组成：筛选期；NKTR-181 开放标签滴定期（每日两次，100 至 400mg）；为期 12 周的随机、双盲研究药物（NKTR-181 或安慰剂）期；一周的研究药物滴定期；两周的安全性随访期。允许使用的解救药物包括氢可酮 5mg/对乙酰氨基酚 300mg（随机分组后每日两片，持续两周），然后在试验的剩余时间内使用对乙酰氨基酚 1.0gm 每日一次。使用临床阿片类戒断量表（COWS）、主观阿片戒断量表（SOWS）、药物滥用、误用和转移事件报告系统（MADDERS）和与戒断相关的不良事件评估药物戒断的体征和症状。

结果

在进入滴定阶段的 1190 名患者中，1 名患者在停用 NKTR-181 三天后出现中度戒断（COWS 评分 13/48 满分）。在 610 名随机分组的患者中（N=309，NKTR-181；N=301，安慰剂），在任何时间点均未观察到 COWS 评分表明中度或更高级别的戒断（即评分≥13）。在随机分组后第 8 天、第 12 周和滴定结束时，安慰剂组分别有 7 名（2.4%）、1 名（0.4%）和 1 名（0.5%）患者出现轻度戒断（<13）COWS 评分，NKTR-181 组分别有 3 名（1.0%）、1 名（0.4%）和 5 名（2.3%）患者出现轻度戒断。在所有时间点，两臂的平均 SOWS 评分均≤64 分中的 2.8 分。在随机治疗期间，MADDERS 识别出 35 个事件，裁决者确定了 20 个可能的“戒断”事件（9 个[2.9%]NKTR-181 和 11 个[3.7%]安慰剂）。