Purpose: Patients with irritable bowel syndrome with diarrhea predominance (IBS-D) have suffered due to a lack of treatment options for men and women. There is emerging interest in serotonin for the treatment of IBS-D. Cilansetron is a 5-HT3 receptor antagonist being developed for the treatment of IBS-D. This study evaluated the efficacy and safety of cilansetron over 3 months in males and females with IBS-D.
Methods: In a double-blind, placebo-controlled study, subjects meeting the Rome criteria for IBS-D received cilansetron 2 mg TID or placebo (P) for 3 months. An interactive voice response system was used to collect weekly data concerning adequate relief of IBS symptoms, abdominal pain/discomfort, and abnormal bowel habits including diarrhea and urgency. The overall responder rate was the proportion of subjects who reported adequate relief on ≥50% of their weekly responses.
Results: The intent-to-treat population included 692 subjects, 205 males and 487 females. Results demonstrated statistically significant efficacy of cilansetron vs P for relieving IBS symptoms (Table 1).
A higher percentage of responders in the cilansetron group vs P reported relief from abdominal pain/discomfort, 52% vs 37% (p <0.001) and relief from abnormal bowel habits including diarrhea and urgency, 51% vs 26% (p <0.001). Both females and males responded to cilansetron. The responder rate for relief of abdominal pain/discomfort for cilansetron vs P was 55% vs 43% (p = 0.008) for females, and 45% vs 23% (p = 0.001) for males and for relief of abnormal bowel habits was 56% vs 29% (p <0.001) for females, and 39% vs 17% (p <0.001) for males.
For cilansetron and P, 12% and 6%, respectively, withdrew due to adverse events (AEs). The most common AEs for cilansetron vs P were constipation (19% vs 4%), abdominal pain (6% vs 1%), and headache (6% vs 3%). No complications of constipation were observed. There was one case of ischemic colitis which resolved in 7 days.
Conclusions: Cilansetron 2 mg TID was well tolerated and significantly improved IBS-D symptoms in both men and women with treatment sustained up to 3 months.