A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP, MULTICENTER TRIAL OF 4 DOSES OF TASOSARTAN IN PATIENTS WITH ESSENTIAL-HYPERTENSION

Tasosartan, a new, long-acting, nonpeptide angiotensin II receptor ant agonist was evaluated in a randomized, double-blind, placebo-controlle d, multicenter trial at 21 sites in the United States and Canada. Afte r a 2-week, placebo washout qualification period, 278 patients (187 me n/91 women) with a mean age of 53.4 +/- 9.5 years (range, 30 to 70 yea rs) and a baseline sitting diastolic blood pressure (DBP) of 95 to 114 mm Hg were randomly assigned to receive placebo (n= 56), or 10 mg (n = 57), 30 mg (n = 55), 100 mg (n =55), or 300 mg (n = 55) tasosartan f or 4 weeks. The treatment period was followed by a 2-week washout peri od. Ambulatory blood pressure (BP) monitoring was performed at the end of the placebo washout period and after at least 4 weeks of double-bl ind treatment. Clinically significant placebo-adjusted differences in baseline sitting systolic blood pressure (SBP)/DBP were observed in th e 10 mg (5/3 mm Hg), 30 mg (5/4 mm Hg), 100 mg (10/7 mm Hg) and 300 mg (10/7 mm Hg) dose groups (P <.05). A dose-response relationship (P <. 001) was observed within 1 to 2 weeks of treatment initiation and was maintained throughout the double-blind period. Discontinuation of taso sartan therapy was not associated with rebound hypertension. Moreover, significant (P < .05) placebo-adjusted differences in ambulatory SBP/ DBP and a significant dose-response relationship (P <.001) were obser ved with all tasosartan dosages during the 24-h, daytime, and nighttim e periods. Placebo-adjusted trough-to-peak ratios ranged from 87% to 1 00% for ambulatory SEP and 64% to 81% for DBP. In general, no signific ant differences were observed between the tasosartan treatment groups and the placebo group in the incidence of adverse events. Headache inc idence was significantly lower in the 300 mg dose group than the place bo group. In conclusion, tasosartan at dosages of 10, 30, 100, or 300 mg given once daily produced a significant and dose-related reduction in both clinic and ambulatory BP that was maintained over the 24-h per iod. Tasosartan was generally well tolerated. (C) 1998 American Journa l of Hypertension, Ltd.