Markman John, Meske Diana S, Kopecky Ernest A, Vaughn Ben, O'Connor Melinda L, Passik Steven D
Department of Neurosurgery, Translational Pain Research Program, University of Rochester, Rochester, NY, USA.
Collegium Pharmaceutical Inc, Canton, MA, USA,
J Pain Res. 2018 Sep 26;11:2051-2059. doi: 10.2147/JPR.S168836. eCollection 2018.
This post hoc analysis of data from a randomized, double-blind, placebo-controlled, enriched-enrollment randomized-withdrawal Phase III study evaluated the safety, tolerability, and analgesic efficacy of Oxycodone DETERx extended-release (ER), abuse-deterrent capsules (Xtampza ER) in subjects with chronic low back pain who were successfully transitioned from immediate-release (IR) oxycodone.
Continuous outcomes were analyzed using a mixed-model repeated-measures approach; binomial outcomes were analyzed using chi-squared; and time-to-event outcomes using Kaplan-Meier analyses.
A total of 110 subjects previously prescribed IR oxycodone entered the Open-label Titration Phase. Forty-four subjects were randomized to Oxycodone DETERx (n=22) or placebo (n=22) in the 12-week Double-blind Maintenance Phase. Efficacy results in this subgroup showed a statistically significant difference between Oxycodone DETERx and placebo in average pain intensity scores from Randomization Baseline to Week 12 (least squares mean [± standard error], -1.88 [0.70]; =0.0078). Additional efficacy results indicated that Oxycodone DETERx vs placebo was associated with a statistically significant benefit in durability of effect from Week 2 through Week 12 (<0.01), numbers of subjects with a ≥30% (n [%] 10 [45.5%] vs 0 [0%]; =0.0004) and ≥50% (10 [45.5%] vs 0 [0%]; =0.0004) improvement in pain intensity, longer time-to-exit (=0.0014), a greater number of subjects who completed the study (14 [63.6%] vs 4 [18.2%]), and less rescue medication use (acetaminophen; mean [SD], 163.5 [337.8] mg) vs 216.2 [377.3] mg). Adverse event profiles were consistent with opioid class effects and results from the original study; Oxycodone DETERx was well tolerated in subjects previously treated with short-acting oxycodone.
Oxycodone DETERx resulted in clinically meaningful and statistically significant efficacy in subjects with chronic low back pain who were previously prescribed IR oxycodone and were successfully switched to ER Oxycodone DETERx.
本项对一项随机、双盲、安慰剂对照、富集入组随机撤药III期研究数据的事后分析，评估了在成功从速释羟考酮转换过来的慢性下腰痛患者中，羟考酮控释（ER）、具滥用威慑作用的胶囊（Xtampza ER）的安全性、耐受性和镇痛疗效。
连续型结局采用混合模型重复测量法进行分析；二项分类结局采用卡方检验进行分析；生存结局采用Kaplan-Meier分析。
共有110名之前服用过速释羟考酮的受试者进入开放标签滴定阶段。44名受试者在12周双盲维持阶段被随机分配至羟考酮控释组（n = 22）或安慰剂组（n = 22）。该亚组的疗效结果显示，从随机化基线至第12周，羟考酮控释组与安慰剂组在平均疼痛强度评分上存在统计学显著差异（最小二乘均值[±标准误]，-1.88 [0.70]；P = 0.0078）。其他疗效结果表明，从第2周至第12周，羟考酮控释组相较于安慰剂组在疗效持久性方面具有统计学显著优势（P < 0.01），疼痛强度改善≥30%的受试者数量（n [%] 10 [45.5%] 对 0 [0%]；P = 0.0004）和≥50%的受试者数量（10 [45.5%] 对 0 [0%]；P = 0.0004）更多，退出时间更长（P = 0.0014），完成研究的受试者数量更多（14 [63.6%] 对 4 [18.2%]），且使用的急救药物更少（对乙酰氨基酚；均值[标准差]，163.5 [337.8] mg对216.2 [377.3] mg）。不良事件谱与阿片类药物的类别效应及原研究结果一致；羟考酮控释在之前接受短效羟考酮治疗的受试者中耐受性良好。
对于之前服用过速释羟考酮且成功转换为羟考酮控释的慢性下腰痛患者，羟考酮控释产生了具有临床意义且统计学显著的疗效。
