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Tenapanor Moves toward Approval for IBS-C Treatment

November 7, 2017
Phase 3 trial participants with constipation-predominant irritable bowel syndrome demonstrated significant benefits in normalized bowel function after taking the experimental inhibitor.

A second Phase 3 trial of tenapanor (T3MPO-2)1 shows promise for relieving symptoms in patients with constipation-predominant irritable bowel syndrome (IBS-C). While there is no current cure, treatment may help to alleviate symptoms, including constipation and severe abdominal pain, in the 11 million Americans diagnosed with IBS-C.2

The 26-week randomized, double-blind, placebo-controlled study run by Ardelyx, a biopharmaceutical manufacturer, met statistical significance in the primary endpoint of percentage of patients with overall response for six of 12 weeks compared to patients who received placebo (36.5% vs 23.7%, p < 0.001).2 According to the study release, orally administered tenapanor selectively inhibits sodium uptake in the intestines as the agent inhibits the sodium-proton exchanger NHE3.2 The result is increased levels of sodium in the intestines, which can lead to higher amounts of fluids in the intestines and consequent stool softening. Tenapanor also appeared to decrease abdominal pain in IBS-C patients.

Constipation and irritable bowel syndromeTenapanor may help reduce symptoms of IBS-C.

The Phase 3 enrolled 593 patients with IBS-C that met the ROME III criteria for diagnosis. Randomization was 1-to-1, and patients received either 50 mg of tenapanor (n=293) or placebo (n=300) twice per day. Enrollment in the trial included a two-week screening period. During this time, patients with active IBS-C recorded in a daily phone diary information about the frequency of bowel movements and the severity of abdominal pain.

Secondary Endpoints Demonstrated Efficacy and Safety

T3MPO-2 met statistical significance for all secondary endpoints as well, according to the study release.2 Patients treated with tenapanor experienced at least a 30% decrease in abdominal pain. Improvements in abdominal pain occurred in the tenapanor group in six of 12 and nine of 12-treatment weeks. Patients in the tenapanor group also experienced increases in one or more complete spontaneous bowel movements (CSBM) in a week for at least six and at least nine of the first 12 weeks. Additional secondary endpoints in which patients receiving tenapanor experienced improvements over placebo included:

  • Percentage of patients with overall response for 13 out of 26 weeks
  • Percentage of patients with overall CSBM response for 13 out of 26 weeks
  • Percentage of patients with overall abdominal pain response for 13 out of 26 weeks
  • Percentage of patients with overall response for nine out of 12 weeks over the first 12 weeks.

Tenapanor was not only found to be efficacious but also safe in the trial, which is consistent with results from previous clinical trials of the agent (eg, NCT01340053). Adverse events observed in greater than 2% of patients in the tenapanor group that occurred at a significantly higher rate than in the placebo group included:

  • Diarrhea (16.0% vs 3.7%)
  • Flatulence (3.1% vs 1.0%)
  • Nasopharyngitis (4.4% vs 3.7%)
  • Abdominal distension (3.4% vs 0.3%).

The placebo-adjusted rate of discontinuation due to diarrhea was 5.8%.

Future Directions for Tenapanor’s Development

Participants who completed the T3MPO-1 and T3MPO-2 trials were eligible to receive tenapanor for up to one year through Ardelyx’s open-label, long-term safety trial, T3MPO-3. T3MPO-3 is fully enrolled and expected to conclude in December 2017.

Ardelyx is also developing tenapanor for the treatment of hyperphosphatemia in patients with end-stage renal disease on dialysis.

Last updated on: November 7, 2017
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