Efficacy and tolerability of once-daily oral fimasartan 20 to 240 mg/d in Korean Patients with hypertension: findings from Two Phase II, randomized, double-blind, placebo-controlled studies

Abstract

BACKGROUND: Fimasartan is a selective angiotensin II receptor blocker developed for once-daily dosing.

OBJECTIVES: To meet the regulatory requirements for approval of an antihypertensive treatment in Korea, this pair of studies was conducted to evaluate the efficacy and tolerability of fimasartan, to determine its dose-response relationship and minimum effective dose, and to characterize its blood pressure (BP)-reduction profile over the dosing interval.

METHODS: These 2 Phase II, randomized, double-blind, placebo-controlled, parallel-group, and dose-response studies enrolled male or nonchildbearing female Korean patients aged 18 to 65 years (study 1) or 18 to 70 years (study 2) with essential hypertension (sitting diastolic BP [DBP] 95-<115 mm Hg [study 1] or 90-<110 mm Hg [study 2]). Patients were randomly assigned to receive fimasartan 20, 60, 120, or 180 mg (study 1) or 20, 60, 120, or 240 mg (study 2) or placebo in the same ratio, once daily for 4 weeks (study 1) or 8 weeks (study 2). Clinic BP was measured at trough, and change from baseline in DBP at week 4 (study 1) or 8 (study 2) was the primary efficacy end point. In study 1, 24-hour ambulatory BP monitoring (ABPM) was conducted. Treatment-emergent adverse events (TEAEs) were assessed using a structured questionnaire, laboratory testing, physical examination, and ECG readings.

RESULTS: Totals of 61 and 195 patients participated in studies 1 and 2, respectively (68% male; mean age, 50.1 and 55.1 years; DBP, 98.7 and 103.6 mm Hg; systolic BP, 147.0 and 158.1 mm Hg), of whom 52 (85.2%) and 169 (86.7%) completed each study. Data from ABPM were obtained from 45 patients (73.8%), and safety profile was evaluated in 225 participants. Four-week treatment with fimasartan 180 mg once daily was associated with a significantly greater mean reduction in DBP compared with placebo in study 1 (-16.4 vs -5.5 mm Hg; P = 0.022). In study 2, fimasartan 60, 120, and 240 mg once daily were associated with significantly greater reductions in DBP after 8 weeks of treatment compared with placebo (-14.4, -14.1, and -12.7 vs -5.8 mm Hg, respectively; P < 0.0001-< 0.005). Fimasartan 60 mg once daily was the minimum effective dose, and the dose-response relationship was flat at doses >60 mg once daily. BP reduction was maintained over the full 24-hour dosing interval (trough-to-peak ratios: 0.41-0.98). The proportions of patients who experienced TEAEs were comparable among the treatment groups in both studies, with headache (9.8%) and dizziness (4.4%) being most commonly reported. No serious AEs were reported.

CONCLUSIONS: Once-daily oral administration of fimasartan was well tolerated and efficacious in reducing BP in these hypertensive Korean patient populations. ClinicalTrials.gov identifiers: NCT00937651 and NCT00923611.