Eluxadoline for Irritable Bowel Syndrome with Diarrhea

Abstract

Background Effective and safe treatments are needed for patients who have irritable bowel syndrome (IBS) with diarrhea. We conducted two phase 3 trials to assess the efficacy and safety of eluxadoline, a new oral agent with mixed opioid effects (μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist), in patients with IBS with diarrhea. Methods We randomly assigned 2427 adults who had IBS with diarrhea to eluxadoline (at a dose of 75 mg or 100 mg) or placebo twice daily for 26 weeks (IBS-3002 trial) or 52 weeks (IBS-3001 trial). 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. Results 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 75 mg of eluxadoline and 100 mg of eluxadoline, as compared with placebo, were nausea (8.1% and 7.5% vs. 5.1%), constipation (7.4% and 8.6% vs. 2.5%), and abdominal pain (5.8% and 7.2% vs. 4.1%). Pancreatitis developed in 5 (2 in the 75-mg group and 3 in the 100-mg group) of the 1666 patients in the safety population (0.3%). Conclusions Eluxadoline is a new therapeutic agent that reduced symptoms of IBS with diarrhea in men and women, with sustained efficacy over 6 months in patients who received the 100-mg dose twice daily. (Funded by Furiex Pharmaceuticals, an affiliate of Allergan; IBS-3001 and IBS-3002 ClinicalTrials.gov numbers, NCT01553591 and NCT01553747 , respectively.).

Eluxadoline: a treatment for IBS with diarrhoea in adults

“…4 Response rates were significantly higher with eluxadoline than placebo after 12 and 26 weeks (p<0.001) (see Figure 1). 3 A response was evident within the first week of treatment and was associated with improved stool consistency and less frequency and urgency. Eluxadoline was associated with greater improvement in abdominal pain and, at the higher dose, reduced bloating.…”

“…The most frequently reported events were constipation (8% with eluxadoline vs 2.5% with placebo), nausea (7.7% vs 5.1%) and abdominal pain (6.5% vs 4.1%). 3 In pooled studies, 1%-2% of patients taking eluxadoline reported somnolence compared with 0.3% taking placebo, but absolute numbers were small. Pancreatitis (two cases at the lower dose of eluxadoline, three at the higher) and sphincter of Oddi spasm (one and seven cases respectively) were reported with eluxadoline but not with placebo.…”

“…3 Eligible patients had IBS with diarrhoea of at least moderate severity with at least mild pain. Loperamide was permitted as rescue medication but was rarely used in any treatment group.…”

The place of eluxadoline in the management of irritable bowel syndrome with diarrhea

“…17 Adult men and women who met Rome III criteria for IBS-D and who had a mean WAP score > 3, mean BSFS ⩾ 5.5, a BSFS ⩾ 5 for at least 5 days, and a mean IBS-D global symptom score of ⩾2 were eligible to participate. Patients were randomized to receive either eluxadoline at a dose of 100 or 75 mg BID or placebo for 26 weeks.…”

Eluxadoline for the treatment of diarrhoea-predominant irritable bowel syndrome

“…The clinical trial data for eluxadoline are also being submitted to other global health and medicines authorities (namely EMA). [40,41,48] …”