FDA approves eluxadoline to treat IBS-D in adults
Irritable bowel syndrome (IBS), which affects 10% to 15% of the U.S. population, can be subcategorized by constipation (IBS-C), diarrhea (IBS-D), or mixed (IBS-M). Few treatment options are available for patients with IBS-D, particularly FDA-approved options that relieve both diarrhea and abdominal pain. On May 27, FDA approved eluxadoline (VIBERZI; Actavis) as a novel treatment option for IBS-D. It has mixed opioid receptor activity and acts on the nervous system to lessen bowel contractions.
Efficacy for eluxadoline was established in two randomized, double-blind, placebo-controlled clinical trials. Both trials demonstrated significant superiority over placebo for the primary endpoint of simultaneous improvement in both abdominal pain and diarrhea at both 75 mg and 100 mg twice-daily doses.
Studies 1 and 2 included identical 26-week periods. A total of 1,281 patients in study 1 and 1,145 patients in study 2 received treatment with eluxadoline 75 mg, 100 mg, or placebo twice daily. Study 1 continued an additional 26 weeks for long-term safety (52 weeks of treatment), followed by a two-week follow-up. Study 2 included a four-week single-blinded placebo withdrawal period upon completion of the 26-week treatment period.
Efficacy of eluxadoline was assessed in both studies using an overall composite responder primary endpoint,which represented a simultaneous improvement in both abdominal pain and diarrhea within a 12-week time interval.
In study 1, the proportion of composite responders in the 100-mg twice-daily treatment group was 8% higher than placebo (P<0.01); in the 75-mg twice-daily treatment group it was 7% higher than placebo (P <0.05).
In study 2, the proportion of composite responders in the 100-mg twice-daily treatment group was 13% higher than placebo (P <0.001) ; in the 75-mg twice-daily treatment group it was 13% higher than placebo (P <0.001).
Results for endpoints were based on patients’ daily electronic diary entries. The proportion of composite responders was similar regardless of sex in both trials. Patients were allowed to take only loperamide as rescue medication for the acute treatment of uncontrolled diarrhea.
The most common adverse effects associated with eluxadoline (>5%) are constipation, nausea, and abdominal pain. There is a potential increased risk for sphincter of Oddi spasm (most cases presented within the first week) and pancreatitis not secondary to sphincter of Oddi spasm. The occurrence of each was <1% and most cases of pancreatitis were related to excessive alcohol intake.
Eluxadoline has not been studied in pregnant women. Animal reproduction studies showed no evidence of any adverse effects on pre- or post-natal development. No data is available regarding the presence of eluxadoline in human breast milk.
No overall differences in effectiveness were observed for the 139 patients >65 years old included in clinical trials; however, a higher proportion of elderly patients experienced adverse reactions. Eluxadoline has not been studied in pediatric patients.
Eluxadoline may produce psychological dependence and is currently awaiting scheduling by the DEA.