Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced top-line results from an initial Phase 2 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<0.05). LX1033 reduced the production of plasma 5-HIAA (a biomarker for serotonin synthesis) significantly more than placebo, with the greatest reductions observed in the 500 mg three times daily dose group. This same LX1033 dose also produced the greatest reduction in abdominal pain, an important measure of efficacy in IBS-d. The proportion of patients showing an abdominal pain intensity weekly response (defined as a reduction in abdominal pain of at least 30% from baseline for at least 50% of the weeks assessed, with no worsening from baseline in stool consistency) was 33% on placebo and 47% on LX1033 500 mg given three times daily (p<0.05). LX1033 was safe and well tolerated in the study, with adverse events evenly distributed among LX1033 treatment arms and placebo.
"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 2a study was underway, we completed long-term toxicology studies which would allow us to conduct a Phase 2b 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 2 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, 1000 mg twice daily, 500 mg twice daily, and 500 mg 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.
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