CLINICAL EFFICACY OF FORCE TITRATED DOSES OF DILTIAZEM EXTENDED-RELEASE - A PLACEBO-CONTROLLED STUDY

Thirty patients with clinical and ambulatory essential hypertension were treated in a double-blind fashion with force titrated doses of placebo or diltiazem once daily (OD) extended-release (ER) 120, 240, 360, and 540 mg to characterize the full-dose range of the new formulation. An incremental dose-response effect was observed both in clinic and ambulatory blood pressure parameters. Doses of greater than or equal to 240 mg significantly decreased clinic diastolic blood pressure, whereas systolic blood pressure was significantly lowered by the 540-mg dose. Moreover, compared with placebo, ambulatory blood pressure was significantly decreased by the 360- and 540-mg dose levels. Trough/peak ratios for systolic and diastolic blood pressures were 50% and higher at dose levels of 240 mg and above. Adverse reactions with diltiazem OD ER were generally mild and similar to those observed with placebo. The findings of this study indicate that the most favorable effects of diltiazem OD ER were observed in response to the 360- and 540-mg dose levels. The dose escalation forced titration study design appears to be a valuable tool in obtaining rigorous dose-response data of new antihypertensive agents.