P0809 - Tenapanor Improves Abdominal Bloating Symptoms in Patients With IBS-C Experiencing Moderate to Severe Bloating

Kyle Staller, MD, MPH¹, Yang Yang, PhD², Suling Zhao, ², Susan Edelstein, PhD²
1Massachusetts General Hospital, Boston, MA; 2Ardelyx, Inc., Waltham, MA

Introduction: Abdominal bloating is one of the most bothersome symptoms of irritable bowel syndrome with constipation (IBS-C), yet it is not a typical primary endpoint in clinical trials. Tenapanor is a first-in-class, minimally systemic inhibitor of intestinal sodium-hydrogen exchanger isoform 3 approved by the US FDA for treatment of IBS-C in adults. Previous studies have demonstrated that tenapanor improves abdominal symptoms in IBS-C. This post hoc analysis assessed the effect of tenapanor on abdominal bloating in patients with IBS-C with moderate to severe bloating.

Methods: Data were pooled from a phase 2b (NCT01923428) and the phase 3 T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) studies, in which patients with IBS-C who met the Rome III criteria were randomized to tenapanor or placebo twice daily (bid) for 12 or 26 weeks. A phone diary was used to collect data on daily abdominal bloating on a scale of 0 to 10, categorized as < 4 (mild), ≥4 to < 8 (moderate), and ≥8 (severe). This analysis examined patients with moderate to severe bloating at baseline from the tenapanor 50 mg bid and placebo groups of the 3 studies (ie, the pooled efficacy analysis set). Efficacy endpoints included the change from baseline in average weekly bloating score and time to onset of achieving a ≥30% and ≥50% reduction from baseline in average weekly bloating score.

Results: In the pooled efficacy analysis set (n=1253), tenapanor treatment resulted in a consistently greater reduction from baseline in average weekly bloating score compared with placebo over the first 12 weeks, with a difference in least-squares mean change of 0.63 in week 8, and 0.56 in week 12 (Figure 1). There was a faster improvement in bloating among those treated with tenapanor compared with those treated with placebo. The median time to onset of achieving a ≥30% reduction in weekly bloating score was 5 weeks for tenapanor-treated patients versus 8 weeks for placebo-treated patients (log-rank test P<0.0001; Figure 2A). Median time to onset of achieving a ≥50% reduction in weekly bloating score is shown in Figure 2B.

Discussion: Tenapanor may be effective in reducing bloating–a persistent and bothersome symptom in a large percentage of patients with IBS-C. The onset of a clinically meaningful reduction can be as early as week 1 and sustains through the duration of treatment.


Figure: Figure 1: Least-Squares Mean Change (LS) From Baseline in Average Weekly Abdominal Bloating Score in Patients With Moderate to Severe Bloating at Baseline (BL).


Figure: Figure 2: Time to Onset of Achieving a (A) ≥30% and (B) ≥50% Reduction in Weekly Bloating Score in Patients with Moderate to Severe Bloating at Baseline.

Disclosures:
Kyle Staller: Ardelyx – Grant/Research Support. Gemelli – Consultant. Laborie – Consultant. Mahana – Consultant. Salix – Consultant. Takeda – Expert witness.
Yang Yang: Ardelyx, Inc – Employee.
Suling Zhao: Ardelyx, Inc. – Employee.
Susan Edelstein: Ardelyx, Inc. – Employee.

Kyle Staller, MD, MPH¹, Yang Yang, PhD², Suling Zhao, ², Susan Edelstein, PhD². P0809 - Tenapanor Improves Abdominal Bloating Symptoms in Patients With IBS-C Experiencing Moderate to Severe Bloating, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.