{Reference Type}: Clinical Trial, Phase II
{Title}: Tenapanor Treatment of Patients With Constipation-Predominant Irritable Bowel Syndrome: A Phase 2, Randomized, Placebo-Controlled Efficacy and Safety Trial.
{Author}: Chey WD;Lembo AJ;Rosenbaum DP;
{Journal}: Am J Gastroenterol
{Volume}: 112
{Issue}: 5
{Year}: 05 2017
{Factor}: 12.045
{DOI}: 10.1038/ajg.2017.41
{Abstract}: Tenapanor is a first-in-class, small-molecule inhibitor of the gastrointestinal sodium/hydrogen exchanger NHE3. This study assessed the efficacy and safety of tenapanor in patients with constipation-predominant irritable bowel syndrome (IBS-C).
In this phase 2, double-blind study, patients with IBS-C (Rome III criteria) were randomized (1:1:1:1) to receive tenapanor 5 mg, 20 mg, or 50 mg b.i.d., or placebo b.i.d. for 12 weeks. The primary end point was the complete spontaneous bowel movement (CSBM) responder rate, defined as the proportion of patients reporting an increase from baseline of ≥1 CSBM/week for ≥6/12 treatment weeks. Secondary end points included abdominal symptom responder rates (≥30% score improvement from baseline for ≥6/12 weeks) and a composite responder rate (CSBM and abdominal pain response in the same week for ≥6/12 weeks).
Overall, 356 patients were randomized (mean age: 45.7 years; 86.8% women) and 304 completed the study. The CSBM responder rate was significantly higher in the tenapanor 50 mg b.i.d. group than in the placebo group (60.7 vs. 33.7%; P<0.001), as was the composite responder rate (50.0 vs. 23.6%; P<0.001). Responder rates for abdominal symptoms (pain, discomfort, bloating, cramping, and fullness) were significantly higher in the tenapanor 50 mg b.i.d. group than in the placebo group (all P<0.05). Diarrhea was the most frequent adverse event (tenapanor b.i.d.: 20 mg, 12.4%; 50 mg, 11.2%).
Tenapanor 50 mg b.i.d. significantly increased stool frequency and reduced abdominal symptoms in patients with IBS-C. Further research into tenapanor as a potential treatment for these patients is justified.