Pharmacopeia drug shows potential as hypertension treatment

PS433540 is a dual-acting angiotensin and endothelin receptor antagonist (DARA) that is being developed as a potential treatment for hypertension and diabetic nephropathy.

The study showed that all doses of PS433540 compared with placebo produced a statistically significant (p<0.01) inhibition of the expected angiotensin II (AII)-induced increase in blood pressure. Additionally, the findings showed that the 250mg and 500mg doses of PS433540 were at least as effective in blocking the AII response as irbesartan, a leading angiotensin receptor blocker for the treatment of hypertension. This AII challenge study was a double-blind evaluation of placebo and four dose levels of PS433540 (20, 100, 250 and 500mg) and open label 300mg of irbesartan in healthy male volunteers. Seventeen subjects received each of the six treatments once, at weekly intervals. At baseline and two, four, 12 and 24 hours post-dose, subjects received a six-minute infusion of AII and had their blood pressure measured. Les Browne, president and CEO of Pharmacopeia, said: "The AII challenge study has been frequently used to confirm the pharmacology and establish the dose for Phase II evaluation of compounds that block the renin-angiotensin system."