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PTU-133 Effect of Eluxadoline on Abdominal and Bowel Symptoms Over Time in Phase 3 Clinical Trials in Patients with Irritable Bowel Syndrome with Diarrhoea (IBS-D)
  1. LA Harris1,
  2. S Lucak2,
  3. L Chang3,
  4. LS Dove4,
  5. PS Covington4
  1. 1Mayo Clinic, Scottsdale
  2. 2Weill Cornell Medicine, New York
  3. 3David Geffen School of Medicine at UCLA, Los Angeles
  4. 4Former employee of Furiex Pharmaceuticals, Inc., an Allergan affiliate, Parsippany, United States

Abstract

Introduction Eluxadoline (ELX) is a mixed µ- and κ-opioid receptor (OR) agonist and δ-OR antagonist. It is locally active and approved for the treatment of IBS-D. Effects of ELX on abdominal pain and stool consistency have been reported based on a composite response; effects on other abdominal and bowel symptoms were evaluated over time.

Methods Two double-blind, placebo (PBO)-controlled, Phase 3 trials (IBS-3001 and IBS-3002) randomised patients (pts) meeting Rome III criteria for IBS-D to twice-daily treatment with ELX 75 or 100 mg or PBO. Pts completed an electronic diary and rated daily IBS symptoms of abdominal discomfort and bloating (both on a 0–10 scale), and recorded numbers of bowel movements (BMs) and episodes of urgency and fincontinence daily through 26 weeks (wks). To assess trajectories of treatment effects over time, daily symptom scores and counts of BMs and episodes of urgency and incontinence were mwith longitudinal analyses. Treatment effect estimates from the models were evaluated at Wks 4, 8, 12, 16, 20, and 24 based on estimated least squares (LS) mean differences (symptom scores) and risk ratios (frequency data).

Results 2428 pts with IBS-D were enrolled across both trials. In both studies, daily abdominal discomfort and bloating scores decreased from baseline within the first wk, with greater reductions seen for ELX. Abdominal discomfort scores were significantly lower (p < 0.05) than PBO for ELX 100 mg at all time points through Wk 24 in both studies (except Wk 4 in IBS-3002), while bloating was significantly lower (p < 0.05) than PBO for ELX 100 mg from Wk 16 onward in both studies (Table). BM frequency and episodes of urgency and incontinence were also reduced from baseline. Both ELX doses significantly reduced (p < 0.05) episodes of urgency compared with PBO at all time points through Wk 24 in both studies. Similarly, ELX significantly reduced BM frequency compared with PBO through 24 wks (data not shown). Episodes of incontinence were significantly lower (p < 0.05) than PBO for both ELX doses from Wk 16 onward in IBS-3002.

Abstract PTU-133 Table 1

Longitudinal analysis of abdominal discomfort and bloating

Conclusion ELX significantly improves abdominal discomfort and bloating, and significantly reduces BM frequency and episodes of urgency and incontinence; effects are sustained through 6 months of treatment.

Reference 1 Previously presented at ACG 2015. Abstract #1761. Am J Gastroenterol 2015;110:S739–S766. doi:10.1038/ajg.2015.275.

Disclosure of Interest L. Harris Grant/research support from: Alvine, Rhythm Pharmaceuticals, Consultant for: Allergan plc, QoL, Ironwood, Conflict with: Ironwood, Allergan plc, S. Lucak Consultant for: Allergan plc, Takeda, Salix, Ironwood, Prometheus, Speaker bureau with: Allergan plc, Takeda, Salix, Ironwood, Conflict with: Allergan plc, Takeda, Salix, Ironwood, L. Chang Conflict with: Ironwood, Allergan plc, Valeant, QOL Medical, Takeda, Ardelyx, Commonwealth Laboratories, AstraZeneca, Synergy, L. Dove Consultant for: Allergan plc, P. Covington: None Declared

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