Pharmacopeia, an innovator in the discovery and development of novel small molecule therapeutics, said it has completed recruitment in its multi-centre phase IIa clinical study of PS433540 (DARA), the company's lead internal product candidate. The objective of the phase IIa randomised, double-blind, placebo-controlled, parallel-group study is to evaluate the efficacy and safety of 200 and 500 mg of PS433540 in subjects with Stage I and Stage II hypertension.
"We have made good progress advancing DARA's clinical development. Not only did we initiate this phase IIa study approximately six months ahead of our original clinical development timeline, but we have now completed enrolment in the study with the expectation of reporting results in the second quarter of 2008," said Les Browne, Ph.D., president and chief executive officer, Pharmacopeia. "As this is the first PS433540 study to include hypertensive patients, we are pleased to have the opportunity to demonstrate that DARA can effectively lower blood pressure in this patient population."
Results from phase I studies of PS433540 in normal subjects have indicated that the compound was well tolerated at all doses up to and including 1,000 mg a day for 14 days. Several studies including the multiple ascending dose (MAD) and angiotensin II challenge studies have shown that PS433540 appears to have a pharmacokinetic profile consistent with once-daily oral administration. In the angiotensin challenge study, 250 and 500 mg of PS433540 fully blocked the increase in blood pressure induced by administration of angiotensin II (AII) to healthy volunteers at least as well as 300 mg of irbesartan, the top dose of the marketed AII antagonist. Numerous similar studies with other agents that block the renin-angiotensin system support that this result is a strong indication that PS433540 can be expected to lower blood pressure in hypertensive patients. Additional data from the MAD study demonstrated that PS433540 produced statistically significant, dose dependent increases versus placebo in plasma-renin activity, as well as reductions in systolic and diastolic blood pressure in non-hypertensive healthy volunteers.
PS433540 is a dual-acting angiotensin (AII) and endothelin (ET1) receptor antagonist 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 in a single compound. There is considerable preclinical and initial clinical data suggesting that compared to either agent alone, simultaneously blocking the actions of both AII and ET1 may provide significantly improved treatment options for several cardiovascular diseases.
Pharmacopeia is a clinical development stage biopharmaceutical company dedicated to discovering and developing novel small molecule therapeutics to address significant medical needs.