Evaluation of Safety and Efficacy in a Twelve-Month Study of Lubiprostone for the Treatment of Chronic Idiopathic Constipation

Purpose: Constipation is a common gastrointestinal condition with limited long-term treatment options. Lubiprostone is a novel type-2 chloride channel (ClC-2) activator that has been shown to be efficacious and well tolerated by patients with chronic constipation in a number of well-controlled clinical trials of 3 to 4 weeks' duration. The primary objective of this study was to evaluate the long-term safety of lubiprostone 24 mcg BID in patients with chronic idiopathic constipation; efficacy endpoints were also evaluated over the duration of treatment. Methods: We conducted a 48-week open-labeled trial in 324 lubiprostone-naïve patients. The majority of patients were female (84.9%) and the mean participant age was 53.2 years. Patients assessed constipation severity and abdominal symptoms of bloating and discomfort using a 5-point scale (0 = absent to 4 = very severe) at each study visit (approximately every 6 weeks). Results: Two-hundred seventeen patients (67%) experienced at least one treatment-related adverse event (AE). The most common treatment-related AEs occurring in ≥2% of the population were nausea (30.2%), diarrhea (19.4%), distention (9.3%), headache (8.6%), flatulence (8.3%), abdominal pain (5.6%), vomiting (4.0%), loose stools (3.4%), dizziness (3.1%), dyspepsia (2.2%), and abdominal discomfort (2.2%). Improvements in assessments of constipation severity, abdominal bloating, and abdominal discomfort were statistically significant at all visits compared to baseline (P <.001). Constipation severity was improved by an average of 1.11 points at Week 1 (N = 320), 1.17 points at Week 24 (N = 183), 1.28 points at Week 48 (N = 152), and 0.99 points for the last on-drug measurement (N = 320). Abdominal bloating was improved by an average of 0.70 points at Week 1 (N = 320), 0.80 points at Week 24 (N = 183), 0.88 points at Week 48 (N = 152), and 0.68 points for the last on-drug measurement (N = 320). Abdominal discomfort was improved by an average of 0.65 points at Week 1 (N = 320), 0.66 points at Week 24 (N = 183), 0.78 points at Week 48 (N = 152), and 0.60 points for the last on-drug measurement (N = 320). Conclusions: These results demonstrate that lubiprostone 24 mcg BID was safe and tolerable. With respect to symptom relief, the results shown in the short-term, double-blinded trials of lubiprostone were similarly observed in this long-term trial and were maintained for at least 48 weeks.