Clinical trial: phase 2 study of lubiprostone for irritable bowel syndrome with constipation

BACKGROUND: Analyses of a trial in constipated patients indicated that lubiprostone may be an effective treatment for irritable bowel syndrome with constipation. AIM: To assess the efficacy and safety of three lubiprostone doses for irritable bowel syndrome with constipation. METHODS: 195 irritable bowel syndrome with constipation patients received daily doses of 16 [8 microg twice daily (b.d.)], 32 (16 microg b.d.) or 48 microg (24 microg b.d.) lubiprostone or placebo b.d. for 3 months. Gastrointestinal parameters were recorded in diaries daily by patients. RESULTS: After 1 month, lubiprostone showed significantly greater improvements in mean abdominal discomfort/pain scores vs. placebo (P = 0.023). After 2 months, all lubiprostone groups showed significantly greater improvements in mean abdominal discomfort/pain scores (P < or = 0.039). After 3 months of treatment, the improvement in each lubiprostone arm was greater than placebo, but the test for trend was no longer significant. Treatment with lubiprostone showed significantly higher rates of gastrointestinal adverse events (P = 0.020), especially diarrhoea and nausea. CONCLUSION: Lubiprostone significantly improved gastrointestinal symptoms of irritable bowel syndrome with constipation at all doses. Higher doses of lubiprostone, especially the 48 microg/day group, were associated with more gastrointestinal adverse events. From these data, the 16 microg/day dose demonstrated the optimal combination of efficacy and safety. These results warrant further study of lubiprostone for treatment of irritable bowel syndrome with constipation patients.