Long-Term Safety and Efficacy of Lubiprostone in Opioid-Induced Bowel Dysfunction in Patients with Chronic, Non-Cancer Pain: Results of a Phase 3, Open-Label Clinical Trial Presidential Poster

Abstract

Purpose: Chronic use of opioid analgesics for the treatment of non-cancer pain results in opioid-induced bowel dysfunction (OBD) in a significant proportion of patients. Lubiprostone, a locally-acting chloride channel (ClC-2) activator, has been shown to counteract the adverse gastrointestinal effects of opioids via this mechanism in nonclinical studies as well as in two 12-week, placebo-controlled clinical trials. The current study evaluates the safety and efficacy of lubiprostone over 9 months of open-label treatment in an OBD patient population. Methods: 439 adult patients (59.9% female) with baseline-confirmed OBD were enrolled from two 12-week, placebo-controlled, double-blinded studies and received lubiprostone, 24 mcg twice daily (BID), for up to 9 months. Inclusion criteria required consistent treatment with a full opioid agonist for the duration of the study. OBD was defined as having, on average, less than 3 spontaneous bowel movements (SBMs)/week, with 25% or more of the BMs having hard to very hard stool consistency, resulting in a sense of incomplete evacuation, and/or associated with moderate or worse straining during the 2-week baseline period. The primary objective of the study was to evaluate the safety of chronic lubiprostone therapy in patients with OBD. Efficacy outcomes were also assessed. Results: Overall, 24.6% of the patients reported treatment-related adverse events (AEs) during the 9-month study, the most common of which were nausea, diarrhea, and headache (5.0%, 4.6%, and 1.6% of patients, respectively). No treatment-related serious AEs were reported. Nausea and diarrhea were cited as reason for withdrawal in 5 (1.1%) and 5 (1.1%) subjects, respectively, and only 2 cases of nausea and 2 cases of diarrhea were rated as severe. Patient reliance on rescue medication was substantially decreased during the course of the study (33.0% of patients reporting use at Month 1 vs. 18.6% at Month 9). Statistically significant changes from baseline were reported at each month for SBM frequency, with mean weekly SBM frequencies ranging from 4.9 to 5.3 SBMs per week as compared to a pre-treatment SBM frequency of 1.4 SBMs per week (p<0.001 vs baseline at all months). Patient ratings of average degree of straining with SBMs, stool consistency, constipation severity, abdominal bloating, abdominal discomfort, and bowel habit irregularity were also statistically significantly improved from baseline during the entire treatment period (p<0.001 at all treatment months). Conclusion: Lubiprostone treatment was well-tolerated and resulted in overall improvement in symptoms and signs of OBD in this 9-month, open-labeled study. Disclosure: Dr. Spierings - Consultant and Advisory Committee/Board Member: Sucampo. Ms. Lindner - Employee: Sucampo. Dr. Woldegeorgis - Employee: Sucampo. Ms. Joswick - Employee: Sucampo. Dr. Ueno - Employee, Stockholder/Ownership Interest, Patent Holder: Sucampo.