The objective of the randomized, double-blind, placebo-controlled, parallel-group study is to evaluate PS433540 safety and efficacy in subjects with Stage I and Stage II hypertension.
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 and an endothelin receptor antagonist in the same molecule.
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 200mg and 500mg) 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.
Les Browne, president and CEO, said: “We are very pleased to have initiated this important Phase IIa concept validation study of PS433540 approximately six months ahead of our original clinical development timeline. The goal of this study is to prove that PS433540 lowers blood pressure in hypertensive patients.”