Abstract 4420: Results of A Double Blind Placebo Controlled Study to Evaluate the Efficacy and Safety of PS433540 in Human Subjects with Hypertension

Abstract

Epidemiologic studies continue to demonstrate extremely disappointing blood pressure (BP) control rates. For this reason, the search for more effective antihypertensive agents continues. PS433540 is the first compound in a novel class of agents called Dual Acting Receptor Antagonists (DARA) which selectively block angiotensin (AT 1 ) and endothelin (ET A ) receptors. In this prospective, randomized, double blind, placebo controlled study, 234 men and women with a mean age of 56.0 years entered a 3– 4 week single blind placebo run-in period. Qualifying stage I or stage II hypertensive patients were randomized in a 1:1:1 ratio to either PS433540 200mg, 500mg or matching placebo for a period of 4 weeks. Ambulatory BP monitoring (ABPM) was performed at the start of the study and was repeated at the end of the treatment period. PS433540 lowered both 24HR Systolic BP (SBP) and Diastolic DBP (DBP) as well as mean office SBP and DBP to a greater extent than placebo, p<0.001. (see Table ) PS433540 was well tolerated with 2 reported serious adverse events in the placebo group and placebo lead-in period. Three patients (all from the placebo group) were discontinued from the study for adverse events. There were no significant laboratory abnormalities. This study demonstrates that PS433540 is an effective and well tolerated new class of antihypertensive agent that may prove to be a very important addition to our armamentarium for the management of hypertension.