Rauck Richard L, Hale Martin E, Bass Almasa, Bramson Candace, Pixton Glenn, Wilson Jacquelyn G, Setnik Beatrice, Meisner Paul, Sommerville Kenneth W, Malhotra Bimal K, Wolfram Gernot
Center for Clinical Research, Carolinas Pain Institute, Winston-Salem, NC, USA Gold Coast Research, LLC, Plantation, FL, USA Pfizer Inc, Durham, NC, USA Pfizer Inc, Groton, CT, USA Duke University Medical Center, Durham, NC, USA Pfizer Inc, New York, NY, USA (B. Setnik is now with INC Research, Raleigh, NC, USA; P. Meisner is now with UCB BioSciences, Raleigh, NC, USA; K. W. Sommerville is now with GW Pharmaceuticals, Research Triangle Park, NC, USA).
Pain. 2015 Sep;156(9):1660-1669. doi: 10.1097/j.pain.0000000000000230.
The objective of this multicenter, double-blind, placebo-controlled, randomized withdrawal study was to evaluate the efficacy and safety of ALO-02, an abuse-deterrent formulation containing pellets of extended-release oxycodone hydrochloride (HCl) surrounding sequestered naltrexone HCl, compared with placebo in the treatment of moderate-to-severe chronic low back pain. An open-label titration period in which all patients received ALO-02 was followed by a double-blind treatment period where patients meeting treatment response criteria were randomized to either a fixed dose of ALO-02 or placebo. Daily average low back pain was assessed using an 11-point numeric rating scale (NRS)-Pain. Of the 663 patients screened, 410 received ALO-02 during the open-label conversion and titration period and 281 patients were randomized to the double-blind treatment period (n = 134, placebo; n = 147, ALO-02). Change in the mean NRS-Pain score from randomization baseline to the final 2 weeks of the treatment period was significantly different favoring ALO-02 compared with placebo (P = 0.0114). Forty-four percent of patients treated with placebo and 57.5% of patients treated with ALO-02 reported ≥30% improvement in weekly average NRS-Pain scores from screening to the final 2 weeks of the treatment period (P = 0.0248). In the double-blind treatment period, 56.8% of patients in the ALO-02 group and 56.0% of patients in the placebo group experienced a treatment-emergent adverse event (TEAE). The most common treatment-related TEAEs for ALO-02 during the treatment period were nausea, vomiting, and constipation, consistent with opioid therapy. ALO-02 has been demonstrated to provide significant reduction of pain in patients with chronic low back pain and has a safety profile similar to other opioids.
这项多中心、双盲、安慰剂对照、随机撤药研究的目的是评估ALO-02（一种含有包埋盐酸纳曲酮的盐酸羟考酮缓释微丸的防滥用制剂）与安慰剂相比，在治疗中度至重度慢性下腰痛方面的疗效和安全性。在一个开放标签滴定期，所有患者均接受ALO-02治疗，随后是双盲治疗期，符合治疗反应标准的患者被随机分配至固定剂量的ALO-02或安慰剂组。使用11点数字评定量表（NRS）-疼痛评估每日平均下腰痛情况。在663例筛查患者中，410例在开放标签转换和滴定期接受了ALO-02治疗，281例患者被随机分配至双盲治疗期（n = 134，安慰剂；n = 147，ALO-02）。从随机化基线至治疗期最后2周，平均NRS-疼痛评分的变化与安慰剂相比，显著有利于ALO-02（P = 0.0114）。从筛查至治疗期最后2周，44%接受安慰剂治疗的患者和57.5%接受ALO-02治疗的患者报告每周平均NRS-疼痛评分改善≥30%（P = 0.0248）。在双盲治疗期，ALO-02组56.8%的患者和安慰剂组56.0%的患者发生了治疗中出现的不良事件（TEAE）。治疗期内与ALO-02治疗相关的最常见TEAE为恶心、呕吐和便秘，与阿片类药物治疗一致。已证明ALO-02可显著减轻慢性下腰痛患者的疼痛，且安全性与其他阿片类药物相似。
