Lexicon Pharmaceuticals has announced top-line results from an initial phase II study exploring the use of LX1033 in diarrhea-predominant irritable bowel syndrome (IBS-d). LX1033 is an investigational drug that inhibits serotonin synthesis in the gastrointestinal tract. Serotonin is a neurotransmitter that has been shown to play a role in the symptoms of irritable bowel syndrome.

The primary endpoint of this study was the change in stool consistency averaged from baseline to day 28. All treatment groups, including placebo, showed significant improvements over time, yet differences between placebo and LX1033 in stool consistency were not statistically significant. Further analyses of the stool consistency data were performed adjusting for early terminations which may have enhanced the placebo response rate.

These additional analyses of stool consistency yielded favorable results for the LX1033 500mg three times daily dose group compared to placebo, and some of these findings were associated with statistically significant results (p

"While LX1033 showed similar improvements in stool consistency as compared to the placebo patients who completed the study, there were positive effects on abdominal pain in the treated group that warrant further study," said Pablo Lapuerta, M.D., Lexicon's chief medical officer. "While this initial phase IIa study was underway, we completed long-term toxicology studies which would allow us to conduct a phase IIb study at doses informed by the current results and with a duration of 12 weeks, a treatment period that has historically been important to identify clinically meaningful changes as compared to placebo."

In this phase II study of IBS-d, 373 patients were randomized to be treated for 28 days with either placebo or one of three different dose levels of LX1033 for 28 days, 1000mg twice daily, 500mg twice daily and 500mg three times daily. The primary endpoint was the change from baseline in stool consistency as evaluated by the Bristol Stool Form Scale. A key secondary endpoint was the change from baseline in abdominal pain, and other endpoints included the change in plasma 5-HIAA.