Abstract
ObjectiveTo evaluate the efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain.DesignProspective, randomized, double-blind, placebo-controlled trial.SettingSeventy-nine US and Canadian centers.SubjectsPatients aged ≥18 years with OIC, defined as <3 spontaneous bowel movements (SBMs) per week.MethodsPatients received lubiprostone 24 mcg or placebo twice daily for 12 weeks. The primary endpoint was change from baseline in SBM frequency at week 8.ResultsAmong 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.ConclusionLubiprostone effectively relieved OIC and associated signs and symptoms and was well tolerated in patients with chronic noncancer pain (http://clinicaltrials.gov/ct2/show/NCT00595946).
Highlights
Chronic pain affects approximately 25–44% of adults in the United States and Europe [1,2,3]
Changes from baseline in spontaneous bowel movements (SBMs) frequency rates were significantly higher at week 8 (P = 0.005) and overall (P = 0.004) in patients treated with lubiprostone compared with placebo
Withdrawals due to adverse events (AEs) were more frequent in the lubiprostone group than in the placebo group (16/210 [7.6%] vs 6/208 [2.9%], respectively), a difference that reached statistical significance (P = 0.046; Fisher’s exact test)
Summary
Chronic pain affects approximately 25–44% of adults in the United States and Europe [1,2,3]. In the United States alone, it is estimated that 100 million adults have chronic pain, resulting in direct and indirect costs of $560–635 billion [4]. Opioid therapy is central to management of moderate-to-severe noncancer pain [5], it is limited by manifestations of opioid-induced constipation (OIC), including straining, hard stools, incomplete evacuation, and abdominal bloating [6]. A systematic review estimated the prevalence of OIC at 41% among patients with chronic noncancer pain [8]. Patients with OIC frequently report that severe constipation imposes an additional quality-of-life burden in addition to their chronic pain [9]. Despite the consequences of uncontrolled OIC, until recently, no medications have been approved by regulatory authorities to treat this condition in patients with chronic noncancer pain. There is a need for therapies with proven safety and efficacy to improve control of OIC
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