Ardelyx has released the first Phase 3 results of their investigational drug tenapanor for the treatment of patients with irritable bowel syndrome with constipation (IBS-C).

Tenapanor is a first-in-class, oral, drug that works by inhibiting the NHE3 transporter in the GI tract to reduce the absorption of dietary sodium into the bloodstream. Blocking NHE3 results in an increase in the amount of sodium in the gut. This increased sodium in the gut leads to an increase of fluid in the gut, which loosens stool, helping to relieve constipation.  

A total of 610 patients with IBS-C took part in the 12-week, randomized, double-blind, placebo-controlled trial, T3MPO-1.  The patients received either 50mg of tenapanor (n=309) or placebo (n=301) twice-daily and included a 4-week randomized withdrawal period.

The primary outcome was a greater combined responder rate (abdominal pain reduction and complete spontaneous bowel movement [CSBM] responder) for tenapanor compared to placebo for six of 12 weeks. 

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Results showed that the endpoint was met with 27% in the tenapanor arm compared to 18.7% in the placebo arm (P=0.02) having at least 30% reduction in abdominal pain and an increase of one or more complete spontaneous bowel movements (CSBMs) in the same week for at least six of the 12 weeks of the treatment period. In the nine of 12 treatment week results, the combined responder rate was 13.7% and 3.3% for the tenapanor and placebo arms, respectively (P<0.001).

However, the individual CSBM responder rate from the six of 12 treatment week results did not demonstrate a statistically significant difference between tenapanor (33.9%) and placebo (29.4%) (P=0.27). Commenting on this, David Rosenbaum, PhD, CEO of Ardelyx said, “The individual CSBM responder rate from the six of 12 week analysis was the one secondary endpoint not met and those data are not consistent with the results from our previous clinical studies. We plan to assess these data alongside the results from T3MPO-2, our six-month Phase 3 study.”

“In this trial, tenapanor demonstrated clinical activity across a large number of study parameters and had a favorable safety profile consistent with previous clinical experience,” said Mike Raab, CEO of Ardelyx. 

A second Phase 3 study of tenapanor is currently ongoing (T3MPO-2). This trial is planned to last 26 weeks and the data is expected to be released in the fourth quarter of 2017. A subsequent third Phase 3 trial is planned to test long-term safety of tenapanor for up to one year; that trial is intended to end in late 2017. 

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