Vondrackova Dana, Leyendecker Petra, Meissner Winfried, Hopp Michael, Szombati Istvan, Hermanns Kai, Ruckes Christian, Weber Susanne, Grothe Birgit, Fleischer Wolfgang, Reimer Karen
CLB FN Bulovka, Praha, Czech Republic.
J Pain. 2008 Dec;9(12):1144-54. doi: 10.1016/j.jpain.2008.06.014. Epub 2008 Aug 16.
This randomized, double-blind, placebo- and active-controlled, parallel-group study was designed to demonstrate the superiority of oxycodone in combination with naloxone in a prolonged release (PR) formulation over placebo with respect to analgesic efficacy. The active control group was included for sensitivity and safety analyses, and furthermore to compare the analgesic efficacy and bowel function of oxycodone PR/naloxone PR with oxycodone PR alone. The analgesic efficacy was measured as the time from the initial dose of study medication to multiple pain events (ie, inadequate analgesia) in patients with moderate to severe chronic low back pain. The full analysis population consisted of 463 patients. The times to recurrent pain events were significantly longer in the oxycodone PR/naloxone PR group compared with placebo (P < .0001-.0003); oxycodone PR/naloxone PR reduced the risk of pain events by 42% (P < .0001; full analysis population). The appearance of pain events was comparable for oxycodone PR/naloxone PR versus oxycodone PR, confirming that the addition of naloxone PR to oxycodone PR in a combination tablet did not negatively affect analgesic efficacy of the opioid. Furthermore, oxycodone PR/naloxone PR offers benefits in terms of an improvement in bowel function. In a therapeutic area of great unmet need, therefore, the combination tablet of oxycodone PR/naloxone PR offers patients effective analgesia while improving opioid-induced bowel dysfunction. Taken together with the observation that the safety profile of oxycodone PR/naloxone PR is consistent with that expected from other opioid analgesics except opioid-induced constipation, these findings indicate that the addition of naloxone to oxycodone in a PR combination tablet offers improved tolerability. Oxycodone PR/naloxone PR is therefore a promising new treatment approach for the management of chronic pain.
This study evaluated the analgesic efficacy and safety of the combination of oxycodone PR/naloxone PR in chronic nonmalignant pain. Opioids are often reduced in dosage or even discontinued as a result of impaired bowel function, leading to insufficient pain treatment. Not only does oxycodone PR/naloxone PR demonstrate analgesic efficacy comparable with oxycodone PR, but it also improves opioid-induced bowel dysfunction, and may therefore improve the acceptability of long-term opioid treatment for chronic pain.
本随机、双盲、安慰剂和活性对照、平行组研究旨在证明羟考酮与纳洛酮的缓释（PR）制剂在镇痛效果方面优于安慰剂。设立活性对照组用于敏感性和安全性分析，此外还用于比较羟考酮PR/纳洛酮PR与单独使用羟考酮PR的镇痛效果和肠道功能。镇痛效果通过中度至重度慢性下腰痛患者从研究药物初始剂量到多次疼痛事件（即镇痛不足）的时间来衡量。全分析人群包括463名患者。与安慰剂相比，羟考酮PR/纳洛酮PR组复发性疼痛事件的时间显著更长（P <.0001-.0003）；羟考酮PR/纳洛酮PR将疼痛事件风险降低了42%（P <.0001；全分析人群）。羟考酮PR/纳洛酮PR与羟考酮PR的疼痛事件出现情况相当，证实了在复方片剂中向羟考酮PR添加纳洛酮PR不会对阿片类药物的镇痛效果产生负面影响。此外，羟考酮PR/纳洛酮PR在改善肠道功能方面具有益处。因此，在一个存在巨大未满足需求的治疗领域，羟考酮PR/纳洛酮PR复方片剂在改善阿片类药物引起的肠道功能障碍的同时为患者提供有效的镇痛。结合羟考酮PR/纳洛酮PR安全概况与除阿片类药物引起的便秘外其他阿片类镇痛药预期情况一致的观察结果，这些发现表明在PR复方片剂中向羟考酮添加纳洛酮可提高耐受性。因此，羟考酮PR/纳洛酮PR是一种有前景的慢性疼痛管理新治疗方法。
本研究评估了羟考酮PR/纳洛酮PR组合在慢性非恶性疼痛中的镇痛效果和安全性。由于肠道功能受损，阿片类药物常被减少剂量甚至停用，导致疼痛治疗不足。羟考酮PR/纳洛酮PR不仅显示出与羟考酮PR相当的镇痛效果，还改善了阿片类药物引起的肠道功能障碍，因此可能提高慢性疼痛长期阿片类药物治疗的可接受性。
