Pharmacopeia Initiates Phase 2 Hypertension Study with PS433540 (DARA)
First internal candidate to enter Phase 2 clinical development
PRINCETON, N.J., Sept. 17 /PRNewswire-FirstCall/ -- Pharmacopeia (Nasdaq: PCOP), an innovator in the discovery and development of novel small molecule therapeutics, today announced the initiation of a Phase 2a clinical study of PS433540, the company's lead internal product candidate. PS433540 is 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 proven mechanisms of action in a single compound. 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. Preclinical studies have shown that PS433540 is highly selective for the AII receptor sub-type 1 and the ET receptor sub-type A. As such PS433540 combines the properties of an angiotensin receptor blocker (ARB) and an endothelin receptor antagonist (ERA) in the same molecule. There are 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.
The objective of the Phase 2a randomized, double-blind, placebo- controlled, parallel-group study is to evaluate the compound's safety and efficacy in subjects with Stage I and Stage II hypertension. This multi- center trial is expected to enroll 170 subjects. After a lead-in period, patients will be randomized into three study arms (placebo and two active arms of 200 mg and 500 mg) receiving PS433540 or placebo once daily for 28 days. Following the four week treatment period, investigators will evaluate the patients' change from baseline in mean 24-hour ambulatory systolic blood pressure; mean 24-hour ambulatory diastolic blood pressure; and mean seated systolic and diastolic blood pressure.
'We are very pleased to have initiated this important Phase 2a concept validation study of PS433540 approximately six months ahead of our original clinical development timeline,' said Les Browne, Ph.D., President and Chief Executive Officer of Pharmacopeia. 'The goal of this study is to prove that PS433540 lowers blood pressure in hypertensive patients.'
Results from the initial Phase 1 trial of PS433540, a single ascending dose (SAD) study, indicated that the compound was well tolerated at all six doses administered ranging from 20 mg to 1,000 mg and that the compound has a half-life that is consistent with once daily administration. In the Phase 1 multiple ascending dose (MAD) study, 4 dose levels ranging from 50 mg to 500 mg did not produce safety or tolerability issues. Consistent with prior guidance, Pharmacopeia expects to report results of an on-going Phase 1 angiotensin II challenge study in September or early in the fourth quarter; and initiate a Phase 1 endothelin challenge study later this year. These studies are designed to evaluate the dual pharmacology of PS433540 in healthy individuals.
'We are approaching this Phase 2a study with great anticipation as it is designed to provide us with important initial indications regarding PS433540's therapeutic potential in patients with cardiovascular disease,' stated Rene Belder, M.D., Pharmacopeia's Vice President of Clinical and Regulatory Affairs.
surf's up......crikey
