Sanders Mark, Jones Stephen, Löwenstein Oliver, Jansen Jan-Peter, Miles Hubert, Simpson Karen
Norfolk and Norwich University Hospital, Norwich, UK.
Althean Pharma Limited, London, UK.
Pain Med. 2015 Aug;16(8):1540-50. doi: 10.1111/pme.12775. Epub 2015 Jun 24.
An international double-blind randomized placebo controlled study evaluated the safety and efficacy of four doses of a new sustained release naloxone capsule to treat Opioid Induced Constipation (OIC).
Forty patients taking opioids for noncancer related pain, and experiencing OIC, were randomized into 4 cohorts of 10 patients. A multiple ascending dose design was used to evaluate the safety and efficacy of 2.5 mg, 5 mg, 10 mg, and 20 mg naloxone sustained release (NSR) capsules vs placebo. Drug was given once-daily for 3 weeks followed by twice daily (bid) dosing between weeks 4 and 6.
The incidence of treatment emergent adverse events was highest in the placebo group. The incidence of adverse events among the four active treatment groups were similar. There were no serious adverse events. The number of severe events was low overall but highest in the placebo group. Significant improvements were seen in Spontaneous Bowel Movements with 5 mg, 10 mg, and 20 mg NSR capsules. Mean change in SBMs from baseline of 2.21 (P = 0.052), 2.37 (P = 0.032); 4.11 (P = 0.0005); 5.19 (<0.0001) was noted with NSR 2.5 mg, 5 mg, 10 mg, and 20 mg, respectively, when taken once daily, compared with 1.38 (P = 0.2) for patients on placebo therapy. No changes in subjective or objective measures of opioid withdrawal as measured by the Subjective Opioid Withdrawal Scale or Clinical Opioid Withdrawal Scale were observed. There was no increase in patient reported pain as measured daily using a visual analogue scale.
This Phase II study has shown that using a new sustained release formulation to deliver oral naloxone to the colon allows successful treatment of OIC without comprising the desired opioid effects.
一项国际双盲随机安慰剂对照研究评估了四种剂量的新型缓释纳洛酮胶囊治疗阿片类药物引起的便秘（OIC）的安全性和有效性。
40名因非癌性疼痛服用阿片类药物且患有OIC的患者被随机分为4组，每组10名患者。采用多剂量递增设计来评估2.5毫克、5毫克、10毫克和20毫克纳洛酮缓释（NSR）胶囊与安慰剂相比的安全性和有效性。药物每日给药一次，持续3周，随后在第4至6周每日给药两次（bid）。
治疗中出现的不良事件发生率在安慰剂组中最高。四个活性治疗组中的不良事件发生率相似。没有严重不良事件。严重事件的数量总体较低，但在安慰剂组中最高。5毫克、10毫克和20毫克NSR胶囊在自发排便方面有显著改善。与接受安慰剂治疗的患者的1.38（P = 0.2）相比，NSR 2.5毫克、5毫克、10毫克和20毫克每日服用一次时，自发排便次数从基线的平均变化分别为2.21（P = 0.052）、2.37（P = 0.032）、4.11（P = 0.0005）、5.19（<0.0001）。通过主观阿片类药物戒断量表或临床阿片类药物戒断量表测量，未观察到阿片类药物戒断的主观或客观指标有变化。使用视觉模拟量表每日测量，患者报告的疼痛没有增加。
这项II期研究表明，使用新型缓释制剂将口服纳洛酮递送至结肠可成功治疗OIC，而不影响所需的阿片类药物效果。
