• Spierings Egilius L H ELH Headache and Face Pain Program, Tufts Medical Center, and Craniofacial Pain Center, Tufts University School of Dental Medicine, Boston, Massachu, Douglas A Drossman, Byron Cryer, Mazen Jamal M M Long Beach VA Medical Center, Long Beach, California, USA., Taryn Losch-Beridon, Shadreck M Mareya, and Martin Wang.
• Headache and Face Pain Program, Tufts Medical Center, and Craniofacial Pain Center, Tufts University School of Dental Medicine, Boston, Massachusetts, USA.
• Pain Med. 2018 Jun 1; 19 (6): 1184-1194.

ObjectiveThe 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.MethodsIn 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.ResultsIn 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.ConclusionsThe 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.

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