Eluxadoline Demonstrates a Lack of Abuse Potential in Phase 2 and 3 Studies of Patients With Irritable Bowel Syndrome With Diarrhea.
OBJECTIVE
Eluxadoline is approved by the Food and Drug Administration for the treatment of adults with irritable bowel syndrome with diarrhea (IBS-D). Eluxadoline is a locally acting mixed μ-opiod and κ-opioid receptor agonist and δ-opioid receptor antagonist. The abuse potential of eluxadoline was evaluated as part of the Phase 2 and 3 clinical trials assessing the efficacy, safety, and tolerability of the drug.


METHODS
One Phase 2 (IBS-2001) and two Phase 3 (IBS-3001 and IBS-3002) randomized controlled trials enrolled patients meeting Rome III criteria for IBS-D. Patients received oral twice-daily double-blind treatment with eluxadoline or placebo for 12, 26, or 52 weeks. The primary end point of these studies 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 days. Safety data were pooled, and specific adverse event terms potentially related to abuse were assessed descriptively. Adverse events reported during a 2-week post-treatment period (IBS-3001) and a 4-week single-blind washout period (IBS-3002) were assessed for signs of opioid withdrawal. Potential withdrawal effects were assessed by using the Subjective Opiate Withdrawal Scale.


RESULTS
Overall, 807 and 1032 patients received 1 or more doses of eluxadoline (75 or 100 mg, respectively), and 975 patients received placebo. The overall incidence of adverse events potentially related to abuse did not differ significantly among the groups given placebo, eluxadoline 75 mg, or eluxadoline 100 mg (2.8%, 2.7%, and 4.3%, respectively). The most common adverse events potentially related to abuse were anxiety and somnolence, which occurred in less than 2% of patients in each group. Median overall Subjective Opiate Withdrawal Scale scores did not differ significantly among the groups given placebo, eluxadoline 75 mg, or eluxadoline 100 mg (3.0, 2.0, and 3.0, respectively).


CONCLUSIONS
In an analysis of data from Phase 2 and Phase 3 trials of eluxadoline (75 or 100 mg) for patients with IBS-D, data revealed no signs of abuse potential for eluxadoline. ClinicalTrials.gov numbers: NCT01130272, NCT01553591, NCT01553747.
Pinney Associates, Bethesda, Maryland. Electronic address: rfant@pinneyassociates.com.
Reginald V
RV
Fant
Pinney Associates, Bethesda, Maryland.
Jack E
JE
Henningfield
Digestive Health Center, University of South Alabama, Mobile, Alabama.
Brooks D
BD
Cash
Former employee of Furiex Pharmaceuticals, Inc, an affiliate of Allergan plc, Parsippany, New Jersey.
Leonard S
LS
Dove
Former employee of Furiex Pharmaceuticals, Inc, an affiliate of Allergan plc, Parsippany, New Jersey.
Paul S
PS
Covington
D000284:Administration, Oral; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003967:Diarrhea / Q000188:drug therapy*; D004311:Double-Blind Method; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects*; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000188:drug therapy*; D010649:Phenylalanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010919:Placebos / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D016037:Single-Blind Method; D019966:Substance-Related Disorders / Q000453:epidemiology*
D005765:Gastrointestinal Agents; D007093:Imidazoles; D010919:Placebos; C583636:eluxadoline; D010649:Phenylalanine
Addiction; Enteric Nervous System; SOWS; Viberzi