PHARMACOPEIA LAUNCHES STUDY OF DARA COMPOUND

Pharmacopeia has announced the initiation of a Phase I clinical study of PS433540, a dual-acting angiotensin and endothelin receptor antagonist (DARA) that is being developed as a potential treatment for hypertension and diabetic nephropathy.

PS433540, the first and only DARA compound in development, possesses two clinically validated mechanisms of action. The compound works by selectively blocking the action of two potent vasoconstrictor and mitogenic agents, angiotensin II (AII) and endothelin 1 (ET1), at their respective receptors. As such PS433540 combines the properties of an angiotensin receptor blocker and an endothelin receptor antagonist in the same molecule. There is considerable preclinical data suggesting that compared with either agent alone, simultaneously blocking the actions of both AII and ET1 may provide significantly improved treatment options for several cardiovascular diseases.

The objective of this randomized, placebo-controlled, dose-escalation study is to evaluate the compound's preliminary safety and tolerability by treating up to seven separate groups of healthy volunteers. Each group will consist of eight people, with six individuals receiving the active DARA compound and two receiving placebo. PS433540 doses administered to the study subjects will increase for each successive group. In addition to safety and tolerability, clinical investigators will also evaluate dose-related pharmacokinetics.