Tenapanor Significantly Reduces Key Abdominal Symptoms in Patients with IBS-C

Anthony Lembo, MD

Credit: Cleveland Clinic

A post hoc analysis of data from a trio of phase 2b and 3 studies of tenapanor in patients with irritable bowel syndrome with constipation (IBS-C) is highlighting the sodium/hydrogen exchanger 3 (NHE3) inhibitor’s ability to significantly reduce key abdominal symptoms, as measured by the novel Abdominal Score.¹

Results published in The American Journal of Gastroenterology call attention to tenapanor’s early onset of action for significantly reducing average weekly scores for abdominal bloating, discomfort, cramping, and fullness versus placebo, with improvements observed as early as week 1 and sustained through week 12.¹

“IBS-C is a clinically heterogeneous disorder, and available treatments may not simultaneously improve both bowel movements and the range of abdominal symptoms that patients experience,” lead investigator Anthony Lembo, MD, of the Digestive Disease Institute at Cleveland Clinic, and colleagues wrote.¹

Although it is the most common disease diagnosed by gastroenterologists, few patients affected by IBS see a provider and receive a diagnosis, and even less report abdominal pain or discomfort resolution with treatment. Although changes in diet and exercise are widely recommended for management of symptoms, medication may also be necessary. However, the exact cause of IBS is unknown, hindering the effective management of its wide array of bothersome abdominal symptoms.^1,2

To determine the overall effectiveness of tenapanor for IBS-associated abdominal symptoms, investigators conducted a post hoc analysis of data from 3 randomized controlled trials, namely NCT01923428, T3MPO-1 (NCT02621892), and T3MPO-2 (NCT02686138). All 3 studies were multicenter, randomized, double-blind, placebo-controlled trials conducted in the United States that enrolled patients who met Rome III criteria for IBS-C.¹

In the present study, data were pooled from the intent-to-treat populations of patients with IBS-C who received tenapanor 50 mg or placebo during the first 12 weeks of treatment. Patients were included in the analysis if they met the individual study eligibility criteria, were randomized, and received ≥1 dose of the study drug.¹

A total of 1372 participants were enrolled, 684 of whom were in the tenapanor 50 mg twice a day group and 688 of whom were in the placebo group. Investigators noted most patients were female (82.4%) and White (65.2%) with a mean age of 45.3 years.¹

Weekly scores were calculated as the average score for all days during a week with ≥4 days of reporting of the given abdominal symptom. In the present analysis, the Abdominal Score was calculated as the average of weekly scores for abdominal pain, discomfort, and bloating. Investigators assessed the overall change from baseline to week 12 for each symptom weekly score and the corresponding Abdominal Score, as well as Abdominal Score 6/12-week and 9/12-week response rates (Abdominal Score improvement of ≥2 points).¹

Upon analysis, the least squares mean Abdominal Score change from baseline in the pooled population was greater with tenapanor compared to placebo over the first 12 weeks of treatment (−2.66 vs −2.09; P <.0001). At week 12, the cumulative distribution of change from baseline in Abdominal Score significantly favored tenapanor over placebo in the pooled population (estimated P <.0001; 99% CI, <.0001 to <.0001).¹

Investigators noted weekly Abdominal Score response rates were consistently greater with tenapanor compared with placebo in the pooled population over the first 12 weeks, and patients receiving tenapanor had significantly increased 6 of 12-week (44.4%) and 9 of 12-week (30.6%) response rates versus patients receiving placebo in the pooled population (32.4% and 20.5%, respectively; both P <.0001). Similar patterns were observed in the individual studies for the 6 of 12-week, 9 of 12-week, and 13 of 26-week response rates.¹

Investigators also observed a significant association between weekly complete spontaneous bowel movement status and weekly Abdominal Score response status each week (P <.0001), with a greater proportion of patients with >0 complete spontaneous bowel movements in a week achieving an Abdominal Score reduction of ≥30%.¹

Diarrhea was the most common event in the pooled population receiving tenapanor (n = 102, 14.8%). The first event of diarrhea occurred mostly within the first month of tenapanor treatment, with a median time to onset of 4.5 (interquartile range, 2 to 23) days.¹

Investigators were careful to note the potential limitation posed by use of the Rome III criteria rather than Rome IV to diagnose and enroll patients in the individual studies, pointing out each of the 3 studies began enrollment before the release of Rome IV criteria. Thus, they raised concerns about the accuracy of the study populations versus the real-world population of patients with IBS-C.¹

Nonetheless, investigators concluded: “We demonstrate that tenapanor significantly improves abdominal symptoms, including pain, bloating, discomfort, cramping, and fullness, in patients with IBS-C, with an early onset of action that increases over time and is sustained throughout the treatment period.”

References:

1. ^{Lembo AJ, Chey WD, Harris LA, et al. Abdominal Symptom Improvement During Clinical Trials of Tenapanor in Patients With Irritable Bowel Syndrome With Constipation: A Post Hoc Analysis. The American Journal of Gastroenterology. doi:10.14309/ajg.0000000000002685}
2. ^{Cleveland Clinic. Irritable Bowel Syndrome (IBS). Diseases & Conditions. November 16, 2023. Accessed March 26, 2024. https://my.clevelandclinic.org/health/diseases/4342-irritable-bowel-syndrome-ibs}