Kawamata Mikito, Iseki Masako, Kawakami Mamoru, Yabuki Shoji, Sasaki Takuma, Ishida Mitsuhiro, Nishiyori Atsushi, Hida Hideaki, Kikuchi Shin-Ichi
Department of Anesthesiology and Resuscitology, Shinshu University School of Medicine, Matsumoto, Japan,
Department of Anesthesiology and Pain Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
J Pain Res. 2019 Jan 17;12:363-375. doi: 10.2147/JPR.S179110. eCollection 2019.
Oxycodone is one of the options for the management of CLBP in patients with an inadequate response to other analgesics. However, oxycodone is not yet approved for noncancer pain in Japan. Here, we assessed the efficacy and long-term safety of S-8117, a controlled-release oxycodone formulation, for the management of Japanese CLBP patients.
An initial enriched enrollment randomized withdrawal, double-blind, placebo-controlled, 5-week phase III trial was conducted across 54 centers in Japan to assess the efficacy of S-8117 vs placebo in moderate-to-severe CLBP patients. Subsequently, a 52-week, open-label, single-arm study was conducted across 53 centers in Japan to evaluate the long-term safety of S-8117. The primary endpoint was the time to inadequate analgesic response during 35 days of the double-blind period. Secondary endpoints were the percentages of patients with inadequate analgesic response, discontinuation rate due to inadequate analgesic effects or AEs, and changes in scores of BPI severity, BPI pain interference, SF-36, and Roland-Morris Disability Questionnaire. Safety was assessed as the incidence of AEs and ADRs.
Of the 189 patients enrolled in the double-blind study, 130 patients who completed the initial titration period were randomized 1:1 to receive either S-8117 (n=62) or placebo (n=68). Baseline characteristics were comparable across the study groups. The time to inadequate analgesic response was significantly longer in patients treated with S-8117 than placebo (=0.0095). Secondary endpoints corroborated the efficacy of S-8117 vs placebo. Overall, 478 AEs were reported in 73/75 patients in the long-term study. The most frequent ADRs were somnolence, constipation, and nausea. No case of drug dependence was reported in the long-term study.
Short-term efficacy vs placebo and long-term safety of S-8117 were demonstrated for the management of Japanese patients with moderate-to-severe CLBP.
对于对其他镇痛药反应欠佳的慢性下腰痛（CLBP）患者，羟考酮是治疗选择之一。然而，在日本羟考酮尚未获批用于非癌性疼痛。在此，我们评估了控释羟考酮制剂S-8117治疗日本CLBP患者的疗效和长期安全性。
在日本的54个中心开展了一项初始富集入组随机撤药、双盲、安慰剂对照的5周III期试验，以评估S-8117对比安慰剂治疗中重度CLBP患者的疗效。随后，在日本的53个中心开展了一项52周的开放标签单臂研究，以评估S-8117的长期安全性。主要终点为双盲期35天内镇痛效果不佳的时间。次要终点为镇痛效果不佳的患者百分比、因镇痛效果不佳或不良事件导致的停药率，以及简明疼痛量表（BPI）严重程度评分、BPI疼痛干扰评分、健康调查简表（SF-36）评分和罗兰-莫里斯残疾问卷评分的变化。安全性评估指标为不良事件（AE）和药物不良反应（ADR）的发生率。
在双盲研究入组的189例患者中，130例完成初始滴定期的患者按1:1随机分组，分别接受S-8117（n = 62）或安慰剂（n = 68）治疗。各研究组的基线特征具有可比性。接受S-8117治疗的患者镇痛效果不佳的时间显著长于接受安慰剂治疗的患者（P = 0.0095）。次要终点证实了S-8117对比安慰剂的疗效。总体而言，长期研究中的75例患者中有73例报告了478例AE。最常见的ADR为嗜睡、便秘和恶心。长期研究中未报告药物依赖病例。
对于日本中重度CLBP患者，S-8117对比安慰剂显示出短期疗效和长期安全性。
