Probiodrug Gesellschaft für Arzneimittelforschung mbH has achieved the third milestone finishing preclinical development of its drug P32/98 for IGT and NIDDM treatment, with respect to starting a clinical phase I trial.

Halle (Saale), Germany //
Probiodrug concludes preclinical development of P32/98.
P32/98 is a potent orally available inhibitor of dipeptidyl peptidase IV (DP IV). The proteolytic enzyme is responsible for the inactivation of the incretins, GIP and GLP-1. Both incretins act in an insulinotropic manner in response to nutrient ingestion. Moreover, GLP-1 has been shown to inhibit in vivo hepatic glucose production, modulate peripheral insulin action and stimulate beta-cell growth in tissue culture.

Administration of DP IV-resistant GLP-1 analogs and exendin-4, a GLP-1 agonist, has demonstrated the potent capacity of these polypeptides to normalize the glycemic state in diabetic animal models as well as in humans. Thus, such polypeptides are under development as potential antidiabetic drugs in several companies.

Similarily, it has been demonstrated that orally administered DP IV-inhibitors, that protecting endogenous incretins from degradation, exhibit the same pleiotropic effects as the externally i.v. administrated peptides GLP-1 or exendin-4.

Hence, P32/98 was developed byprobiodrug as its first antidiabetic drug candidate. Milestones during preclinical development were GMP-conform drug and tablet production, pharmacology and toxicology, according to GLP-requirements. Toxicological studies in two species revealed no adverse properties of the drug even at high doses. Pharmacological studies comparing conventional drugs to the effects of P32/98 on crucial diabetic parameters such as acute glucose control after OGTT, morning blood glucose, HbA1c and insulin response in a longer term trial using a diabetic animal model exhibited the excellent antidiabetic properties of the drug.

Probiodrug has now finished all prerequisites to enter the first clinical trial assessing safety, tolerability, and administration and elimination kinetics in healthy volunteers which has been ethically approved in September 1999.