US-based biopharmaceutical firm Lexicon Pharmaceuticals has released top-line results from an initial Phase II trial, designed to assess the use of its investigational drug LX1033 in diarrhea-predominant irritable bowel syndrome (IBS-d).
The drug that inhibits serotonin synthesis in the gastrointestinal tract neutralises the hormone’s role in the symptoms related to irritable bowel syndrome.
A total of 373 patients were randomised in the trial to be treated for 28 days with either placebo or one of three different dose levels of LX1033 for 28 days, 1,000mg twice daily, 500mg twice daily, and 500mg three times daily.
The primary endpoint of the trial was the change in stool consistency averaged from baseline to day 28, while the secondary endpoint was the change from baseline in abdominal pain, and other endpoints included the change in plasma 5-HIAA.
In the trial, all treatment groups, including placebo, showed significant improvements over time, yet differences between placebo and LX1033 in stool consistency were not statistically significant.
Additional analyses of the stool consistency data were carried out adjusting for early terminations which may have improved the placebo response rate.
The analyses yielded favourable results for the LX1033 500mg three times daily dose group compared to placebo, and some of these findings were related with statistically significant results (p<0.05).
The trial showed that the drug helped in reducing the production of plasma 5-HIAA (a biomarker for serotonin synthesis) significantly more than placebo, with better reductions observed in the 500mg three times daily dose group.
The same drug dose also produced reduction in abdominal pain, an important measure of efficacy in IBS-d.
In the trial, LX1033 was safe and well tolerated, with adverse events evenly distributed among LX1033 treatment arms and placebo.
Lexicon chief medical officer Pablo Lapuerta said while LX1033 showed similar improvements in stool consistency as compared with the placebo patients who completed the study, there were positive effects on abdominal pain in the treated group that warrant further study.
"While this initial Phase 2a study was underway, we completed long-term toxicology studies that 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," Lapuerta said.