Randomized Clinical Trial: Crofelemer Treatment in Women With Diarrhea-Predominant Irritable Bowel Syndrome

Abstract

Introduction: Crofelemer, the active compound purified from latex of Croton lechleri, has been shown to improve HIV and traveler's diarrhea and improve pain in women with irritable bowel syndrome-diarrhea (IBS-D). This trial evaluated the effect of crofelemer on abdominal pain in women with IBS-D.

Methods: Women with IBS-D were randomized to crofelemer (125 mg) or placebo twice daily for 12 weeks. The primary efficacy endpoint was overall change in percentage of abdominal pain/discomfort-free days. Post hoc analysis for Food and Drug Administration (FDA) monthly responders was performed for stool consistency, abdominal pain, and combined stool consistency and abdominal pain.

Results: A total of 240 women were enrolled. There was no significant difference in overall percentage of pain/discomfort-free day between the groups. In post hoc analysis, FDA abdominal pain monthly responders were significantly more likely during months 1 through 2 (58.3% vs 45.0%, P = 0.030) as well as during the entire 3 months (54.2% vs 42.5%, P = 0.037) in the crofelemer group when compared with placebo. However, there was no significant difference in the percentage of FDA stool consistency monthly responders or combined stool consistency and pain monthly responders between the groups. Crofelemer had a safety profile similar to placebo.

Discussion: Crofelemer did not significantly improve abdominal pain over placebo by the primary endpoint. However, it did based on the FDA abdominal pain monthly responder endpoint. This suggests that crofelemer may have a role in the treatment of abdominal pain associated with IBS-D. Further studies are warranted to evaluate the potential of crofelemer as a visceral analgesic.

Trial registration: ClinicalTrials.gov NCT00461526.

Figure 1.

Patient flow through the trial.

Figure 2.

There were no significant differences with respect to FDA stool consistency and abdominal pain monthly responders between women in the crofelemer and placebo groups (P = 0.32, 0.28, 0.36 for months 1, 2, and 3). There were no significant differences in stool consistency monthly responders between women in the crofelemer and placebo treatment groups (P = 0.62, 0.76, 0.51 for months 1, 2, and 3). In months 1 and 3, there were no significant differences in percentage of FDA abdominal pain monthly responders between the crofelemer and placebo treatment groups (P = 0.23 for month 1 and P = 0.07 for month 3). In month 2, there were significantly more FDA abdominal pain monthly responders in the crofelemer group when compared with the placebo group. (a) There was no significant differences with respect to FDA stool consistency and abdominal pain monthly responders between the crofelemer and placebo groups (P = 0.32, 0.28, 0.36 for months 1, 2, and 3). (b) In months 1 and 3, there were no significant differences in percentage of FDA abdominal pain monthly responders between the crofelemer and placebo treatment groups (P = 0.23 for month 1 and P = 0.07 for month 3). (c) In month 2, there were significantly more abdominal pain monthly responders in the crofelemer group compared with the placebo group. FDA, Food and Drug Administration.

Figure 3.

A significantly greater percentage of women in the crofelemer group were FDA abdominal pain responders during months 1, 2, and 3 when compared with the placebo group (54.2% vs 42.5%, P = 0.037). A greater percentage of women were also FDA abdominal pain responders for 2 of 3 months. By contrast, a greater percentage of women in the placebo group were FDA abdominal pain responders for 0 of 3 months and 1 of 3 months. *Indicates statistical significance. FDA, Food and Drug Administration.