Nepadutant (MEN 11420) is a glycosilated bicyclic hexapeptide, obtained by total synthesis and exceptionally stable to metabolic degradation. Nepadutant is a potent and selective antagonist at the tachykinin NK2 receptor, and showed a very good safety and tolerability profile in preclinical and clinical studies. Nepadutant is being developed as an intravenous therapy for post-operative ileus (POI).

POI is the prolonged inhibition of gastrointestinal motility that routinely occurs following abdominal, pelvic or thoracic surgery. It can take days or weeks to resolve. During this time, patients are neither able to tolerate oral feeding, nor have bowel movements, and can suffer from nausea, vomiting and pain. The occurence of POI also results in prolonged hospitalization with rising health care costs. Currently, there is no effective pharmacological treatment for POI.

Nepadutant has demonstrated to regulate intestinal motility and to be active on visceral pain, both in preclinical and clinical studies, without altering basal parameters in healthy subjects. In particular, nepadutant was active in a preclinical model of POI, significantly shortening the time to full recovery of motility. In addition, in a phase IIa study in humans, nepadutant prevented both the alterations of intestinal motility and the noxious symptoms produced by prolonged infusion of neurokinin A.

Regulatory phase I
clinical studies with intravenous nepadutant have been completed.