Lubiprostone improves opioid-induced constipation without affecting opioid analgesia

Abstract

The use of opioids to manage chronic pain may be limited by constipation. Lubiprostone is a locally-acting, type-2 chloride channel activator indicated to treat chronic idiopathic constipation in adults at 24 mcg twice daily (BID). We assessed the safety and efficacy of lubiprostone for treating opioid-induced constipation (OIC) in patients with chronic, noncancer pain. Patients required opioids ≥30 days before and during the study and had <3 spontaneous bowel movements (SBMs)/week during screening. Patients (N=443) were randomized to receive lubiprostone 24 mcg BID or placebo for 12 weeks. The primary efficacy endpoint was change from baseline in SBM frequency at week 8 in patients without study medication dose reductions. Mean changes in morphine equivalent daily dose were similar (P≥.18) in the lubiprostone and placebo groups (months 1, 2, and 3). Mean changes in Brief Pain Inventory-Short Form scores were similar (P≥.0667) in both groups at all times, except for significantly less pain interference at month 2 with lubiprostone (P=.0114). Mean increase in SBM frequency was significantly greater with lubiprostone vs. placebo at week 8 (P=.0188) and overall (P=.0047). Higher percentages of patients treated with lubiprostone vs. placebo reported their first SBM within 24 and 48 hours (significant at 24 [P=.0235] but not 48 hours [P=.0566]). Significant improvements were observed for constipation severity, stool consistency, abdominal discomfort, and straining (all P≤.0246, lubiprostone vs. placebo). The most common adverse events (AEs) with lubiprostone and placebo were nausea (16% vs 6%), diarrhea (10% vs. 3%), and abdominal distension (8% vs. 2%); few patients (6% vs. 3%) discontinued because of an AE and none died. Lubiprostone was well-tolerated and improved SBM frequency without changing analgesic response in patients with chronic noncancer pain and OIC. Supported by Sucampo Pharma Americas, Inc. and Takeda Pharmaceuticals, USA. The use of opioids to manage chronic pain may be limited by constipation. Lubiprostone is a locally-acting, type-2 chloride channel activator indicated to treat chronic idiopathic constipation in adults at 24 mcg twice daily (BID). We assessed the safety and efficacy of lubiprostone for treating opioid-induced constipation (OIC) in patients with chronic, noncancer pain. Patients required opioids ≥30 days before and during the study and had <3 spontaneous bowel movements (SBMs)/week during screening. Patients (N=443) were randomized to receive lubiprostone 24 mcg BID or placebo for 12 weeks. The primary efficacy endpoint was change from baseline in SBM frequency at week 8 in patients without study medication dose reductions. Mean changes in morphine equivalent daily dose were similar (P≥.18) in the lubiprostone and placebo groups (months 1, 2, and 3). Mean changes in Brief Pain Inventory-Short Form scores were similar (P≥.0667) in both groups at all times, except for significantly less pain interference at month 2 with lubiprostone (P=.0114). Mean increase in SBM frequency was significantly greater with lubiprostone vs. placebo at week 8 (P=.0188) and overall (P=.0047). Higher percentages of patients treated with lubiprostone vs. placebo reported their first SBM within 24 and 48 hours (significant at 24 [P=.0235] but not 48 hours [P=.0566]). Significant improvements were observed for constipation severity, stool consistency, abdominal discomfort, and straining (all P≤.0246, lubiprostone vs. placebo). The most common adverse events (AEs) with lubiprostone and placebo were nausea (16% vs 6%), diarrhea (10% vs. 3%), and abdominal distension (8% vs. 2%); few patients (6% vs. 3%) discontinued because of an AE and none died. Lubiprostone was well-tolerated and improved SBM frequency without changing analgesic response in patients with chronic noncancer pain and OIC. Supported by Sucampo Pharma Americas, Inc. and Takeda Pharmaceuticals, USA.