Novel delivery system for verapamil designed to achieve maximal blood pressure control during the early morning

Because the risk of cardiovascular events appears to be greatest in the early morning, this period is a time during which adequate blood pressure (BP) control appears to be most desirable. In this study, a controlled-onset extended-release system (COER-24) that delivers verapamil in a manner designed to achieve maximal levels of drug during the early morning surge in BP was compared with placebo. Ninety-five patients with mild to moderate hypertension were studied. Of this group, 49 patients (mean age 57.6 ± 1.4 years; 35 men and 14 women) were randomized to take verapamil COER-24 240 mg at 10 , and 46 subjects (mean age 55.8 ± 1.5 years; 29 men and 17 women) were randomized to take placebo. Ambulatory BP monitoring was performed after a 4-week initial placebo period and was repeated after 4 weeks of treatment with verapamil or placebo. Verapamil COER-24 resulted in significant (p < 0.001) decreases in mean whole-day systolic and diastolic BP (−8.2/−6.3 mm Hg; baseline152/93.0 mm Hg) when compared with placebo (+0.3/−0.9 mm Hg; baseline 150.3/93.2 mm Hg). From 6 to noon, verapamil COER-24 resulted in a change in systolic and diastolic BP of −11.6/−9.0 mm Hg, which was significantly (p < 0.001) greater than the change that occurred with placebo (−0.5/−1.0 mm Hg) during the same period. In the last 4 hours of the dosing interval (6 to 10 ), verapamil COER-24 caused significantly greater (p < 0.001) decreases in BP (−7.4/−4.8 mm Hg) than did placebo (+2.7/+1.0 mm Hg). These data demonstrate that the COER-24 system, when administered in the late evening, achieves maximal BP reduction during the early morning hours. Moreover, BP reductions were sustained throughout the 24-hour period.