Results of a multicenter, 8-week, parallel-group, randomized,double-blind, double-dummy, phase III clinical trial to evaluate the efficacy and tolerability of amlodipine maleate versus amlodipine besylate in Korean patients with mild to moderate hypertension

Abstract

BACKGROUND: Recently, amlodipine maleate was developed and tested in preclinical and Phase I clinical trials in Korea. The studies found pharmacokinetics and pharmacodynamics similar to those of amlodipine besylate. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of amlodipine maleate with those of amlodipine besylate in Korean patients with mild to moderate hypertension. METHODS: This was a multicenter, 8-week, parallel-group, randomized, double-blind, double-dummy, Phase III clinical trial. Eligible patients were Korean, aged 18 to 75 years, had hypertension, and were either taking antihypertensive medications or had a documented sitting diastolic blood pressure of 90 to 109 mm Hg. After a washout period of 2 weeks, patients were randomized to amlodipine maleate or amlodipine besylate for 8 weeks. In both groups, the medications were initiated at 5 mg QD. At day 29, the medication dose was increased to 10 mg QD if sitting diastolic blood pressure (SiDBP) was > or = 90 mm Hg. RESULTS: One hundred eighteen patients were enrolled. Fifty-seven patients received amlodipine maleate (29 men, 28 women; mean [SD] age, 49.0 [11.4] years) and 61 received amlodipine besylate (35 men, 26 women; mean [SD] age, 51.6 [9.4] years). Baseline mean (SD) values for sitting systolic blood pressure and SiDBP were 152.0 (12.2) mm Hg and 98.1 (5.6) mm Hg, respectively, for the amlodipine maleate group and 153.4 (14.0) mm Hg and 98.1 (5.5) mm Hg, respectively, for the amlodipine besylate group. In this population, amlodipine maleate was not inferior to amlodipine besylate: the lower limit of the 2-sided 95% CI for the treatment difference in SiDBP was greater than -4 mm Hg. The between-group difference in SiDBP response rate (the proportion of patients who experienced adequate SiDBP reductions) did not reach statistical significance: 85.7% (42/49) for the amlodipine maleate group and 91.8% (45/49) for the amlodipine besylate group. Compliance rates were similar between groups, with mean (SD) compliance rates of 97.4% (2.8%) and 97.1% (3.6%) in the amlodipine maleate and amlodipine besylate groups, respectively. Also, there were no significant differences in the incidences of drug-related clinical and laboratory adverse events; the most common were headache, flushing, facial edema, and paresthesia. CONCLUSION: In this population, the efficacy and tolerability observed with amlodipine maleate were similar to those seen with amlodipine besylate.