A multicenter, randomized, double-blind Phase III study has revealed that a combination of amlodipine and candesartan cilexetil (AML/CC) is more effective than amlodipine (AML) monotherapy in treating essential hypertension in Korean patients. The trial, designed to secure approval from the Korean Ministry of Food and Drug Safety (KMFDS) for the fixed-dose combination, demonstrated superior antihypertensive efficacy and comparable safety.
Study Design and Patient Population
The study enrolled adult men and women aged 19–75 years with essential hypertension from 20 institutions in Korea between December 2014 and July 2015 (NCT02368665). Participants underwent a 4-week run-in period with AML (5 mg) before being randomized (1:1) to either AML/CC combination therapy or AML monotherapy for an 8-week treatment period. Patients with a diastolic blood pressure (DBP) ≥90 mmHg and <120 mmHg after the run-in period were included. Key exclusion criteria included secondary hypertension, severe heart disease, cerebrovascular disorders, and significant bilateral blood pressure differences.
Efficacy Outcomes
The primary efficacy outcome was the change in DBP at week 8 from baseline. Secondary outcomes included changes in DBP at week 4 and changes in systolic blood pressure (SBP) at weeks 4 and 8 from baseline. An extension treatment arm evaluated changes in DBP and SBP at weeks 12 and 16 compared to week 8 in patients assigned to combination therapy. The combination of AML 10 mg and CC 16 mg was used in the study.
The least square (LS) mean change in baseline-adjusted DBP from baseline to after 8 weeks of study treatment and its standard error (SE) were presented. The inter-arm superiority test was conducted using the analysis of covariance (ANCOVA) with change in the DBP from baseline after 8 weeks of treatment as the response variable and the baseline DBP and treatment arm as independent variables. The same statistical approach was applied to the change in DBP at week 8 and in SBP at weeks 4 and 8.
Safety and Tolerability
The occurrence of adverse events (AEs) was monitored to assess safety. Treatment compliance was evaluated by counting remaining pills at each visit. The safety profile of the AML/CC combination was found to be comparable to that of AML monotherapy.
Statistical Analysis
Statistical analysis was performed using SAS (version 9.3). The primary efficacy analysis involved an analysis of covariance (ANCOVA) to compare changes in DBP between the treatment groups. A p-value < 0.05 was considered statistically significant.
Clinical Implications
The results of this Phase III trial support the use of AML/CC fixed-dose combination as an effective and well-tolerated treatment option for patients with essential hypertension whose blood pressure is not adequately controlled with AML monotherapy. The study's rigorous design and comprehensive evaluation of efficacy and safety outcomes provide robust evidence for the clinical benefit of this combination therapy.
