Ardelyx, Inc. (NASDAQ: ARDX), a clinical-stage biopharmaceutical company focused on cardio-renal, gastrointestinal, and metabolic diseases, today presented Phase 2b clinical trial results that demonstrated statistically significant and clinically meaningful improvement in IBS-C symptoms for tenapanor-treated patients compared to patients receiving placebo. As previously reported, at the 50 mg dose of tenapanor, the study met its primary efficacy endpoint of an increase in the complete spontaneous bowel movement (CSBM) responder rate. Most secondary endpoints, including abdominal pain and other abdominal and IBS-C symptoms, demonstrated clinically meaningful improvements. Tenapanor was well-tolerated, and the safety results were consistent with those observed in previous tenapanor trials.
The findings were presented today in an oral presentation entitled, "Efficacy and Safety of Tenapanor in Patients with Constipation Predominant Irritable Bowel Syndrome: A 12-Week, Double-Blind, Placebo-Controlled, Randomized Phase 2b Trial" at the Digestive Disease Week (DDW) 2015 conference being held in Washington, D.C. from May 16-19, 2015.
"IBS-C impacts the quality of life of millions of patients yet is still one of the most enigmatic diseases of the gut," said William Chey, MD, Professor of Internal Medicine at University of Michigan. "Tenapanor, if successfully developed, would represent an entirely new mechanism of action for the treatment of IBS-C that could give patients important options for their disease."
"More than 14 million people worldwide are estimated to suffer from IBS-C, many of whom are not effectively treated by current marketed therapies," said Mike Raab, President & Chief Executive Officer of Ardelyx. "Based on tenapanor's clinical results through the Phase 2b program, we believe that it has the potential to offer a best-in-class treatment for this underserved population."
Phase 2b Clinical Trials for Tenapanor in IBS-C
The Phase 2b clinical trial was a randomized, double blind, placebo-controlled, multi-center study to evaluate the safety and efficacy of three dose levels of tenapanor in 356 subjects with IBS-C as defined by the Rome III criteria and who had active disease as determined during a two-week screening period. Subjects who qualified and who were randomized into the study received 5, 20, or 50 mg of tenapanor or placebo twice daily for 12 consecutive weeks. At the end of this treatment period, subjects were followed for an additional 4 weeks. The primary endpoint, overall CSBM responder rate, was achieved in 60.7 percent of patients receiving tenapanor 50 mg twice daily versus 33.7 percent receiving placebo (p < 0.001). A responder was defined as a patient who had an increase of greater than or equal to one CSBM from baseline during 6 out of 12 weeks. The results are reported on an intent-to-treat basis.
The overall abdominal pain responder rate was achieved in 65.5 percent of patients receiving tenapanor 50 mg twice daily versus 48.3 percent receiving placebo (p = 0.026). An overall abdominal pain responder was defined as a patient who experienced at least a 30 percent decrease in abdominal pain from baseline for 6 of 12 weeks.
The overall responder rate, or dual composite endpoint percent, was achieved in 50.0 percent of patients receiving tenapanor 50 mg twice daily versus 23.6 percent receiving placebo (p < 0.001). An overall responder was defined as a patient who was both an overall CSBM responder and an overall abdominal pain responder in the same week for 6 of 12 weeks.
As shown in the table, other key secondary endpoints that exhibited significant improvements for patients receiving 50 mg tenapanor twice daily compared to placebo-treated patients included abdominal discomfort, abdominal bloating, straining, stool consistency, CSBM per week and SBM per week.
Phase 2b Primary and Key Secondary Endpoints
A dose response relationship among all doses was observed in the primary endpoint, as well as in most secondary endpoints, although statistical significance was not achieved at the 5 mg or 20 mg doses. Additionally, the activity of tenapanor was maintained throughout the entire 12-week treatment period.
Tenapanor was well-tolerated in these patients, and the safety results were consistent with those observed in previous tenapanor trials. The most common adverse events at 50 mg twice daily (greater than or equal to 5 percent) that occurred more frequently in tenapanor-treated patients compared to placebo-treated patients were diarrhea at 11.2 percent vs. 0 percent, and urinary tract infections at 5.6 percent vs. 4.4 percent. Overall rates of discontinuation due to adverse events were 4.5 percent (3.3 percent due to diarrhea) for the tenapanor-treated patients (50 mg twice daily) and 3.3 percent for the placebo-treated patients. Based on the analysis of plasma samples tested as part of the study, the minimally systemic nature of tenapanor was confirmed.
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