A Randomized Study of Lubiprostone for Opioid-Induced Constipation in Patients with Chronic Noncancer Pain

OBJECTIVE To evaluate the efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain. DESIGN Prospective, randomized, double-blind, placebo-controlled trial. SETTING Seventy-nine US and Canadian centers. SUBJECTS Patients aged ≥ 18 years with OIC, defined as <3 spontaneous bowel movements (SBMs) per week. METHODS Patients received lubiprostone 24 mcg or placebo twice daily for 12 weeks. The primary endpoint was change from baseline in SBM frequency at week 8. RESULTS Among randomized patients (N=418; lubiprostone, N=210; placebo, N=208), most completed the study (lubiprostone, 67.1%; placebo, 69.7%). The safety and efficacy (intent-to-treat) populations included 414 (lubiprostone, N=208; placebo, N=206) and 413 (lubiprostone, N=209; placebo, N=204) patients, respectively. The mean (standard deviation) age was 50.4 (10.9) years; most patients were female (64.4%) and white (77.7%). Changes from baseline in SBM frequency rates were significantly higher at week 8 (P=0.005) and overall (P=0.004) in patients treated with lubiprostone compared with placebo. Pairwise comparisons showed significantly greater overall improvement for abdominal discomfort (P=0.047), straining (P<0.001), constipation severity (P=0.007), and stool consistency (P<0.001) with lubiprostone compared with placebo. Moreover, patients rated the effectiveness of lubiprostone as significantly (P<0.05) better than placebo for 11 of 12 weeks. The most common treatment-related adverse events (AEs) with lubiprostone and placebo were nausea (16.8% vs 5.8%, respectively), diarrhea (9.6% vs 2.9%), and abdominal distention (8.2% vs 2.4%). No lubiprostone-related serious AEs occurred. CONCLUSION Lubiprostone effectively relieved OIC and associated signs and symptoms and was well tolerated in patients with chronic noncancer pain (http://clinicaltrials.gov/ct2/show/NCT00595946).