Clinical Trial: Study to Investigate the Efficacy and Safety of the Alpha-2-Delta Ligand PD-217,014 in Patients With Irritable Bowel Syndrome

Abstract

Introduction

Despite the emergence of drugs to treat irritable bowel syndrome (IBS), improving abdominal pain can still be challenging. α₂δ ligands, such as gabapentin and pregabalin, are sometimes used off-label to tackle this problem. However, evidence for efficacy is limited, and no large-scale studies have been published.

Aim

To study the efficacy of the α₂δ ligand PD-217,014 in IBS.

Methods

This multi-centre, double-blind, randomised, placebo-controlled, parallel group study randomised participants with Rome II-defined IBS to 150 or 300 mg b.d. of PD-217,014 or placebo b.d. for 4 weeks. The primary efficacy endpoint was responder, defined as having adequate relief of abdominal pain/discomfort for ≥ 50% of the active treatment period. Key secondary endpoints were change from baseline in abdominal pain, bloating, stool frequency/consistency, and global assessment of IBS symptoms.

Results

We randomised 330 participants [aged 19–73 years; 209 (65%) female] satisfying Rome II criteria, 322 (98%) were treated, and of whom 271 (84%) completed the study. In this study, 321 satisfied Rome IV criteria. Neither dose of PD-217,014 improved the percentage of participants reporting adequate relief of abdominal pain/discomfort compared with placebo, either using the Rome II-defined total cohort or Rome II and IV IBS bowel habit sub-types. There were similar observations for secondary endpoints, and no association between abdominal pain or anxiety levels at baseline with participant improvement. PD-217,014 was generally well tolerated.

Conclusion

This first large, dose-ranging trial examining the efficacy of PD-217,014 showed no significant efficacy in participants with IBS or bowel habit sub-types, irrespective of their pain and anxiety levels.