Tenapanor, an investigational, minimally systemic, small-molecule NHE3 inhibitor, was well tolerated and improved symptoms in patients with constipation-predominant irritable bowel syndrome in the first of two phase 3 clinical trials, the manufacturer Ardelyx announced.
“We’re pleased to have achieved the primary endpoint in the T3MPO-1 trial,” Mike Raab, president and CEO of Ardelyx, said in a press release. “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. With a differentiated mechanism of action, we believe tenapanor has the potential to augment the care of patients with IBS-C.”
This was a multicenter, double blind trial in which researchers randomly assigned 610 patients with IBS-C to receive either 50 mg tenapanor or placebo twice per day for 12 weeks. There was also a 2-week screening period and a 4-week randomized withdrawal period.
Researchers defined responders as having at least a 30% decrease in abdominal pain and an increase of at least one complete spontaneous bowel movement (CSBM) in the same week for at least 6 of the 12 treatment weeks. The combined responder rate served as the primary endpoint, which 27% of the treatment group achieved vs. 18.7% of the placebo group (P = .02).
The trial also achieved significance for seven of eight secondary endpoints assessing abdominal pain and CSBM responders individually as well as durable response for 9 of the 12 treatment weeks including at least 3 of the last 4.
The drug was well tolerated and the most common adverse events were diarrhea, occurring in 14.6% of the treatment group vs. 1.7% of the placebo group, and nausea, occurring in 2.6% and 1.7%, respectively. Further, 5.9% of the treatment group stopped treatment due to adverse events compared with 0.6% of the placebo group based on preliminary data.
“When we look at the totality of the topline results from T3MPO-1, we believe tenapanor has the potential to offer benefit to patients with IBS-C,” David Rosenbaum, PhD, chief development officer of Ardelyx, said in the press release. “We are encouraged that the 9 of 12 week data demonstrate a durable and sustained response for constipation and abdominal pain, as well as a normalization of bowel movement frequency, for many patients. The individual CSBM responder rate from the 6 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 6-month phase 3 study, to evaluate the total benefit that tenapanor may provide to patients with this extremely challenging condition.”
This second phase 3 trial is ongoing, and the company expects results in the fourth quarter of this year. Patients who complete these initial phase 3 trials are eligible to enter a third open-label, long-term safety trial evaluating treatment for up to a year, with completion expected in late 2017.
Disclosures: Rosenbaum and Raab are employed by Ardelyx.