A phase-3 trial assessed the long-term efficacy and safety of tenapanor 50 mg b.i.d. for the treatment of patients with IBS with constipation (IBS-C). This drug is the first in class, minimally absorbed, small molecule inhibitor of the gastrointestinal sodium/ hydrogen exchanger isoform-3.
In this randomized, double-blind study, patients with IBS-C received tenapanor 50 mg b.i.d. or placebo b.i.d. for 26 weeks.The primary endpoint was the proportion of patients who had a reduction of greater than 30% in average weekly worst abdominal pain and an increase greater than 1 weekly complete spontaneous bowel movement from baseline, both in the same week for greater than 6 of the first 12 treatment weeks (6/12 week combined responder).
A total of 620 randomized patients were included with IBS-C; 593 were included in the intention-to-treat analysis set (N = 293), placebo (N = 300), and 481 patients completed the 26-week treatment period. In the intention-to-treat analysis set, a significantly greater proportion of patients treated with tenapanor were 6/12 week combined responders than those treated with placebo (36.5% vs. 23.7%). Abdominal symptoms and global symptoms of IBS were significantly improved with tenapanor, compared with placebo.
Diarrhea, the most common adverse event (AE), was typically transient and mild to moderate in severity. Diarrhea led to study drug discontinuation for 19 (6.5%) and 2 patients receiving tenapanor and placebo, respectively.
It was concluded that tenapanor 50 mg b.i.d. improved IBS-C symptoms over 26 weeks and was generally well tolerated, offering a potential new long-term treatment option for patients with IBS-C.