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LAS VEGAS -- A specific dose of tenapanor, an investigational drug that reduces absorption of dietary sodium and phosphate, may help patients suffering from irritable bowel syndrome with constipation (IBS-C), a researcher reported here.
Results from a randomized phase IIb trial of 356 patients with IBS-C found that those taking a twice-daily dose of 50 mg of tenapanor, compared with placebo, experienced more complete spontaneous bowel movements (60.7% versus 33.7%, P<0.001), said , of the University of Michigan in Ann Arbor, at the 2016 meeting.
"It seemed very efficacious and it seems like something that could be used in refractory patients," panel moderator of Brigham and Women's Hospital in Boston, said of the drug for IBS-C symptoms.
Chey explained that tenapanor, if approved, would be the first IBS-C drug to inhibit the Na+/H+ isoform 3 exchanger in the gut, which regulates sodium absorption and, via downstream effects, phosphate absorption as well. Previous studies have suggested that such an action could help stimulate bowel movements in constipation. Chey also noted that systemic absorption of tenapanor in pharmacokinetic studies appeared to be minimal.
The study included 356 IBS-C patients diagnosed under criteria, who had <3 complete spontaneous bowel movements and <5 spontaneous bowel movements per week, as well as a Likert Scale abdominal pain score ≥ 3. All patients -- 87% women, mean age 45.7 years -- were randomized to receive two daily doses of tenapanor at 5 mg (n=87), 20 mg (n=87), or 50 mg (n=84), or placebo (n=89).
Chey said the groups were well matched "in terms of key baseline clinical demographics ... this was a severely affected group." Across the treatment arms, there were a mean of 0.2 complete spontaneous bowel movements and an average of two spontaneous bowel movements per week; median IBS severity rating was 3.9 on a five-point scale.
While the lower doses of the drug showed no significant benefit over placebo, Chey and colleagues noticed a rapid and sustainable separation between 50 mg tenapanor and placebo over the 12-week period. Patients in the tenapanor cohort experienced a 65.5% abdominal pain responder rate compared with 48.3% in the placebo group (P=0.026). There was also a significant difference between tenapanor and placebo in the overall responder rate (50% versus 23.6%, P<0.001).
Patients in the 50 mg tenapanor cohort demonstrated statistically significant improvement in several global efficacy endpoints: IBS severity, constipation severity, adequate IBS symptom relief, degree of IBS symptom relief, and treatment satisfaction.
On a patient-reported endpoint of adequate global symptom relief, 63.1% of the high-dose group versus 39.3% of the placebo group said "yes" (P=0.002).
With respect to safety, Chey said, "Overall, the drug was very well tolerated. I think one thing that everybody always wonders about is the diarrhea rate in drugs used to treat constipation ... the diarrhea rate was quite modest, in the range of 10% or less." He did not provide other details on adverse events, however, as his presentation focused on efficacy outcomes.
Next up for tenapanor is a phase III trial with the 50-mg dosage, Chey said.
Disclosures
The study was supported by Ardelyx.
Chey and Lembo reported consulting for Ardelyx.
PharmaGenesis provided editorial assistance.
Primary Source
American College of Gastroenterology
Chey W, et al "The effect of tenapanor on global endpoints in patients with constipation predominant irritable bowel syndrome: results from a 12-week, double-blind, placebo-controlled, randomized phase 2b trial (64)" ACG 2016; Abstract 64.