NicOx S.A. has announced that its Investigational New Drug application (IND) has been accepted by the US Food and Drug Administration (FDA) for the Phase II clinical testing of NCX 4016, its patented nitric oxide-donating derivative of aspirin, in development for the treatment and prevention of cardiovascular diseases.

The IND will allow expansion of NicOx's broad development program for NCX 4016 in the field of cardiovascular and metabolic diseases, which includes diabetes-related renal and vascular complications, and the treatment of endothelial dysfunction in patients with peripheral vascular disease. In total, the Phase II development program will involve the recruitment of approximately 120 patients by mid- 2003.

Following today's announcement, a Phase IIa trial with 12 patients is planned to start in November in type 2 diabetes patients with endothelial dysfunction. The randomized, double-blind, repeated-dose, cross-over study will evaluate the effects of repeated 4-week administration of NCX 4016 compared with equimolar doses of aspirin on markers of renal damage and safety in patients with type 2 diabetes and early nephropathy.

NCX 4016 has already been successfully tested in a Phase I/IIa clinical study, demonstrating a unique cardiovascular anti-inflammatory profile and excellent overall safety in a well standardized human clinical model of vascular inflammation, platelet and coagulation activation induced by lipopolysaccharide (LPS) infusion. Excellent gastric safety in humans after repeated doses (one week) up to 800mg bid (twice a day) was shown in a Phase I clinical endoscopic study.

Giancarlo Santus, Nicox' Vice-President, Product Development, commented: "The acceptance of this IND for NCX 4016 and the extension of the Phase II clinical trials in the treatment of renal and vascular complications of diabetes demonstrate the strong scientific rationale for the development of NCX4016 in the cardiovascular field. Pre-clinical studies, together with Phase I clinical data on more than 200 subjects, have shown that NCX 4016 has an excellent gastro-intestinal and cardiovascular profile, as well as a unique pharmacological profile. With these characteristics, NCX 4016 has the potential to represent a significant advance in the treatment and prevention of cardiovascular diseases."