Headache and Face Pain Program, Tufts Medical Center, and Craniofacial Pain Center, Tufts University School of Dental Medicine, Boston, Massachusetts, USA.
University of North Carolina at Chapel Hill, and Drossman Gastroenterology, Chapel Hill, North Carolina, USA.
Pain Med. 2018 Jun 1;19(6):1184-1194. doi: 10.1093/pm/pnx156.
The efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain were evaluated in a randomized, double-blind, placebo-controlled study. These data were also pooled with those from two similar phase 3 studies to explore the effects of methadone on treatment response.
In the primary study, adults with OIC (fewer than three spontaneous bowel movements [SBMs] per week) were randomized to receive lubiprostone 24 mcg or placebo twice daily for 12 weeks. The primary end point was a change from baseline in the frequency of SBMs at week 8 in patients without a prior dose reduction. For the pooled analysis, the efficacy of lubiprostone was compared with placebo in patients receiving methadone or nonmethadone opioids. Responders were defined as patients with nine or more weeks of nonmissing SBM data who had one or more additional SBMs per week from baseline for each week that data were available and three or more SBMs per week for nine or more weeks.
In the primary study, the change from baseline at week 8 in SBM frequency was similar in the lubiprostone and placebo groups (P = 0.842). In the pooled analysis, the response rate was significantly higher with lubiprostone treatment vs placebo for patients receiving nonmethadone opioids (P = 0.002) but was similar between lubiprostone treatment and placebo in patients receiving methadone (P = 0.692). The safety profile of lubiprostone was unaffected by methadone use.
The phase 3 study did not meet its primary efficacy end point. However, analysis of pooled data from all phase 3 studies in the OIC clinical development program, stratified by methadone opioid usage, confirmed that lubiprostone is effective for treatment of OIC in patients taking nonmethadone opioids; no safety concerns were identified based on the type of opioid used.
评估口服鲁比前列酮治疗慢性非癌痛患者阿片类药物诱导的便秘（OIC）症状的疗效和安全性，该研究为一项随机、双盲、安慰剂对照研究。这些数据还与两项类似的 3 期研究的数据进行了汇总，以探讨美沙酮对治疗反应的影响。
在主要研究中，OIC 患者（每周自发性排便次数[SBM]少于 3 次）被随机分为两组，分别接受鲁比前列酮 24μg，每日 2 次，或安慰剂，治疗 12 周。主要终点是在没有剂量减少的情况下，第 8 周时 SBM 频率相对于基线的变化。对于汇总分析，比较了鲁比前列酮和美沙酮或非美沙酮类阿片类药物治疗患者的疗效。应答者定义为每周有 9 周或以上非缺失 SBM 数据，并且在可用数据的每一周中，与基线相比每周增加一次或以上 SBM，且每周 SBM 达到 3 次或以上的患者。
在主要研究中，与安慰剂组相比，鲁比前列酮组在第 8 周时 SBM 频率的变化从基线开始无显著差异（P=0.842）。在汇总分析中，与安慰剂相比，接受非美沙酮类阿片类药物治疗的患者中，鲁比前列酮治疗的应答率显著更高（P=0.002），而接受美沙酮治疗的患者中，鲁比前列酮治疗与安慰剂的应答率相似（P=0.692）。鲁比前列酮的安全性不受美沙酮使用的影响。
3 期研究未达到主要疗效终点。然而，对 OIC 临床开发计划中所有 3 期研究的汇总数据进行分析，按美沙酮类阿片类药物的使用情况进行分层，证实鲁比前列酮对接受非美沙酮类阿片类药物治疗的 OIC 患者有效；基于使用的阿片类药物类型，未发现安全性问题。
