Su1384 A Retrospective Assessment of Area Under the Pain Curve in Quantifying Daily Pain Assessments in Irritable Bowel Syndrome With Diarrhea

Abstract

Background & Aims: Eluxadoline (ELX) is a locally active, mixed mu opioid receptor agonist and delta opioid receptor antagonist which was shown to improve the symptoms of irritable bowel syndrome with diarrhea (IBS-D) in 2 Phase 3 trials. With respect to abdominal pain, we performed additional prospective analyses to further examine efficacy on pain in IBS-D. Methods: Two double-blind, placebo-controlled, Phase 3 clinical trials (3001 and 3002) enrolled patients meeting Rome III criteria for IBS-D to twice-daily treatment with ELX (75 or 100 mg) or placebo (PBO). Both clinical trials had identical designs through 26 weeks of treatment. The primary endpoint was a composite response based on simultaneous daily improvement in worst abdominal pain (WAP) and stool consistency over Weeks 1-12 (Food and Drug Administration [FDA] endpoint) and Weeks 1-26 (European Medicines Agency [EMA] endpoint). Additional prospective analyses of WAP (scale of 010) included: Cochran-Mantel-Haenszel (CMH) assessments of WAP responders, defined as patients with ≥50% of days with ≥30% improvement (at the study level and pooled); longitudinal analyses (LA) of WAP response rates and of WAP daily scores, both at specific time points and at the study level; assessment of pooled data using CMH analyses of WAP responders over the 2 intervals based on 40% and 50% improvements in pain; and analysis of covariance (ANCOVA) assessment of change from baseline (CFB) in WAP daily scores of the pooled data at specific time points. Results: 2428 patients with IBS-D were enrolled across the 2 trials. Significantly more patients receiving ELX (75 mg and 100 mg) were FDA and EMA responders compared with patients receiving PBO (p 30% pain improvement for >50% of days), significant differences between ELXand PBO-treated patients were present for LA of WAP responders at Week 26 for ELX 75 mg in both studies and for ELX 100 mg in Study 3002 (Table 1). Likewise, LA of WAP scores at Week 26 achieved significance for ELX 100 mg in both studies at both time points. CMH analyses from the pooled data showed significant differences for ELX 100 mg over PBO for WAP responders at both the >40% and >50% pain improvement levels (Table 2). Findings were similar for the ANCOVA CFB WAP score analysis of the pooled data. Conclusions: Results from 2 Phase 3 clinical trials demonstrated that ELX showed statistically significant improvement in treating the abdominal pain component of IBS-D. This was particularly evident for ELX 100 mg, with ≥40% pain improvement definition for responders. This was further supported by results of the LA of pain response rates and LA of pain scores at the study level and ANCOVACFB analyses from the pooled data. Table 1. Study-specific pain analyses