Efficacy and safety of PPC-5650 on experimental rectal pain in patients with irritable bowel syndrome.

Abstract

PPC-5650 is a new pharmacological agent that can modulate acid-sensing ion channel activity, leading to a reduction in the pain signal under up-regulated conditions. The non-clinical programme for PPC-5650 supported a role for this novel agent in the treatment of pain in patients with irritable bowel syndrome (IBS). In patients with IBS, the aims of the study were: (1) to assess the efficacy of a single bolus of PPC-5650 locally applied in the rectum using multi-modal stimulations of the recto sigmoid and (2) to assess the safety profile of PPC-5650. The study was a randomized, double-blind, placebo-controlled, cross-over trial in patients with IBS, excluding females of child-bearing potential. The study consisted of a training visit, study visit 1 and 2 and a follow-up visit. Rectosigmoid electrical, thermal and mechanical stimulations were performed, pain perception was rated on a pain intensity scale and referred pain areas were assessed. All adverse events were registered. Twenty-five patients with IBS were enrolled and completed the study (9 women and 16 men; mean age 50.4±12.7years). No effects of the study drug were found on any of the rectal stimulations or for referred pain areas (all p>0.05). No significant or clinically relevant treatment-related differences were seen for the laboratory safety variables or any other reported adverse event. In conclusion, in patients with IBS on rectal sensitivity to multi-modal stimulations, PPC-5650 did not produce efficacy relative to placebo. The overall safety and tolerability of PPC-5650 was acceptable.