Phase III results for a new oral drug to treat patients with IBS and diarrhoea show a decrease in symptoms compared to placebo, but any benefit will need to be considered in the context of side effects and risks, the authors say.

Marketed by Furiex Pharmaceuticals, an affiliate of Allergan, eluxadoline (Viberzi) works on the μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist and was approved by the FDA last year.

Published in this week’s New England Journal of Medicine the two phase III trials involved 2,427 patients with IBS with diarrhoea who were randomized to either 75 mg or 100 mg of eluxadoline twice daily or placebo for 26 weeks for trial 1 and 52 weeks for trial 2.

The primary end point was the proportion of patients who had a composite response of decrease in abdominal pain and improvement in stool consistency on the same day for at least 50% of the days from weeks 1 through 12 and from weeks 1 through 26.

For weeks 1 through 12, more patients in the eluxadoline groups (75 mg and 100 mg) than in the placebo group reached the primary end point (IBS-3001 trial, 23.9% with the 75-mg dose and 25.1% with the 100-mg dose vs. 17.1% with placebo; P=0.01 and P=0.004, respectively; IBS-3002 trial, 28.9% and 29.6%, respectively, vs. 16.2%; P<0.001 for both comparisons).

For weeks 1 through 26, the corresponding rates in IBS-3001 were 23.4% and 29.3% versus 19.0% (P=0.11 and P<0.001, respectively), and the corresponding rates in IBS-3002 were 30.4% and 32.7% versus 20.2% (P=0.001 and P<0.001, respectively).

The most common adverse events associated with both doses of eluxadoline were nausea and constipation.

Five cases of pancreatitis and 8 cases of abdominal pain with elevated levels of hepatic enzymes were reported.

All cases of pancreatitis did not involve organ failure or local or systemic complications, occurred in patients with either biliary disorders (spasm of the sphincter of Oddi and biliary sludge) or alcohol use (3 of 5 cases), and resolved within the first week after the onset of pancreatitis.

However the presence of only mild cases does not preclude the risk of severe cases in the future, nor do these associations preclude other at-risk populations, the study authors wrote.

“Identifying patients with IBS with diarrhoea who are at risk for acute pancreatitis because of the absence of a gallbladder or excessive alcohol consumption is important before initiating therapy with eluxadoline” they cautioned.

“Any benefit will need to be considered in the context of side effects and risks.”

 The studies were funded by Furiex pharmaceuticals.