Evaluation of the dose-response relationship of amlodipine and losartan combination in patients with essential hypertension: An 8-week, randomized, double-blind, factorial, phase II, multicenter study

Background: Despite recommendations for more intensive treatment and the availability of several effective treatments, hypertension remains uncontrolled in many patients. Objective: The aim of this study was to determine the dose-response relationship and assess the efficacy and safety of amlodipine or losartan monotherapy and amlodipine camsylate/losartan combination therapy in patients with essential hypertension. Methods: This was an 8-week, randomized, double-blind, factorial design, phase II, multicenter study conducted in outpatient hospital clinics among adult patients aged 18-75 years with essential hypertension. At screening, patients received placebo for 2-4 weeks. Eligible patients (n = 320) were randomized to one of eight treatment groups: amlodipine 5mg or 10 mg, losartan 50mg or 100 mg, amlodipine camsylate/losartan 5mg/50 mg, 5mg/100 mg, 10 mg/50 mg, or 10 mg/100 mg. Main Outcome Measures: The assumption of strict superiority was estimated using the mean change in sitting diastolic blood pressure (DBP) at 8 weeks. Safety was monitored through physical examinations, vital signs, laboratory test results, ECG, and adverse events. Results: The reduction in DBP at 8 weeks was significantly greater in patients treated with the combination therapies compared with the respective monotherapies for all specified comparisons except amlodipine camsylate/losartan 10 mg/100mg versus amlodipine 10 mg. The incidence of adverse events in the group of patients treated with the amlodipine camsylate/losartan 10 mg/50 mg combination tended to be higher than for any other group (27.9%, 12/43); however, the effect was not statistically significant. Conclusion: Combination amlodipine camsylate/losartan (5 mg/50 mg, 5mg/100mg and 10 mg/50 mg) resulted in significantly greater BP lowering compared with amlodipine or losartan monotherapy, and was determined to be generally safe and tolerable in patients with essential hypertension.