Effect of Fimasartan versus Valsartan and Olmesartan on Office and Ambulatory Blood Pressure in Korean Patients with Mild-to-Moderate Essential Hypertension: A Randomized, Double-Blind, Active Control, Three-Parallel Group, Forced Titration, Multicenter,

Head-to-head comparison of the blood pressure (BP) lowering effect of fimasartan versus valsartan, with olmesartan as a reference, on office blood pressure and ambulatory BP. Of the 369 randomly assigned patients in this study, 365 hypertensive patients were referred as the full analysis set and divided into 3 groups with a 3:3:1 ratio (fimasartan group: 155, valsartan group: 157, olmesartan group: 53). After the 2-week single-blind placebo run-in period, initial standard doses of 60-mg fimasartan, 80-mg valsartan, and 10-mg olmesartan were administered for 2 weeks, then forcibly up-titrated higher doses (fimasartan 120 mg, valsartan 160 mg, olmesartan 20 mg) were given for 4 weeks. ABP was measured before and after the 6-week treatment. Primary endpoint was reduction of sitting office systolic BP (SiSBP) of fimasartan compared to valsartan after 6 weeks. Secondary endpoints were reduction of sitting office diastolic BP (SiDBP) and 24 hrs, day-time, and night-time mean systolic and diastolic ABP (ASBP, ADBP) after 6 weeks. Patients' mean age was 58.34±7.68 years, and 289 patients were male (79.18%). After the 6-week treatment, SiSBP reduction of fimasartan and valsartan were -16.26±15.07 and -12.81±13.87 (p=0.0298) and SiDBP were -7.63±9.67 and -5.14±8.52 (p=0.0211). Reductions in 24 hrs mean ASBP were -15.22±13.33 and -9.45±12.37 (p=0.0009), and ADBPs were -8.74±7.55 and -5.98±7.85 (p=0.0140). Reductions of night-time ASBPs were -16.80±15.81 and -10.32±14.88 (p=0.0012), and those of night-time ADBPs were -8.89±9.93 and -5.55±9.70 (p=0.0152). Reduction of BP in olmesartan group did not demonstrate significant difference with fimasartan group in all end-points. Fimasartan 120-mg treatment demonstrated superior efficacy in reduction of SiSBP, SiDBP, and 24 hrs ASBP and ADBP compared to valsartan 160 mg. Reduction of night-time ASBP from baseline was largest in fimasartan group, suggesting that fimasartan may be effective for recovering dipping pattern. NCT02495324 (Fimasartan Achieving SBP Target (FAST) study).

Chung WB ，Ihm SH ，Jang SW ，Her SH ，Park CS ，Lee JM ，Chang K ，Jeon DS ，Yoo KD ，Seung KB ... -  《Drug Design Development and Therapy》

Ambulatory blood pressure response to once-daily fimasartan: an 8-week, multicenter, randomized, double-blind, active-comparator, parallel-group study in Korean patients with mild to moderate essential hypertension.

Fimasartan, a selective angiotensin II type 1 receptor blocker, was approved in Korea for the treatment of patients with mild to moderate hypertension. The aim of this study was to evaluate the 24-hour blood pressure (BP) profiles before and after 8-week treatment with fimasartan and to compare them with those of valsartan. A multicenter, randomized, double-blind, active-controlled, parallel-group study was conducted using ambulatory BP monitoring (ABPM). Korean patients with mild to moderate essential hypertension were enrolled and randomly received once-daily oral fimasartan 60 or 120 mg or valsartan 80 mg for 8 weeks. ABPM was performed before and after 8-week treatment, and clinic BP was also measured. Based on ABPM data, trough-to-peak ratio and smoothness index were derived. Tolerability was monitored throughout the study. Ninety-two patients were enrolled (mean [SD] age, 54.1 [8.2] years; weight, 67.9 [10.2] kg). After 8 weeks, 24-hour, daytime, and nighttime mean ambulatory systolic and diastolic BPs (SBP and DBP, respectively) were significantly decreased in all 3 treatment groups (range: SBP, -9.2 to -15.6 mm Hg; DBP, -5.0 to -10.7 mm Hg; P <0.0001-<0.05). The global trough-to-peak ratios of ambulatory DBP in the fimasartan groups were 0.74 (60 mg/d) and 0.81 (120 mg/d)--45.1% and 58.8% higher, respectively, than the ratio of 0.51 in the valsartan group. Fimasartan 60 mg/d was associated with 53.5% (SBP) and 68.3% (DBP) greater smoothness index scores compared with those with valsartan 80 mg/d (SBP, 1.52 vs. 0.99; DBP, 1.38 vs. 0.82). The decrease in clinic-measured DBP was significantly greater in the fimasartan 60-mg/d group compared with that in the valsartan 80-mg/d group (-14.0 vs -8.7 mm Hg; P = 0.0380). Fimasartan was well tolerated; headache was the most common adverse event. Once-daily fimasartan effectively maintained a BP-reduction profile over the full 24-hour dosing interval; this profile was comparable to or slightly better than that of once-daily valsartan. Fimasartan was well tolerated; headache was the most common adverse event.

Lee H ，Kim KS ，Chae SC ，Jeong MH ，Kim DS ，Oh BH ... -  《-》

Efficacy and safety of 30-mg fimasartan for the treatment of patients with mild to moderate hypertension: an 8-week, multicenter, randomized, double-blind, phase III clinical study.

The standard 60-mg dose of fimasartan, a newly developed selective angiotensin II receptor blocker, is effective and safe for use in patients with mild to moderate hypertension. This study aimed to compare the efficacy and safety of low-dose (30 mg) fimasartan and placebo or valsartan (80 mg) for 8 weeks in patients with mild to moderate hypertension. In this randomized trial, 293 patients (219 men; mean age, 54.24 [9.77] years) with mild to moderate hypertension were enrolled. After randomization to receive 30-mg fimasartan (n = 115), placebo (n = 117), or 80-mg valsartan (n = 61), the treatment dose was kept constant without dose escalation for 8 weeks. The primary end point was improvement in sitting diastolic blood pressure (SiDBP) from baseline to 8 weeks that was compared between treatments with low-dose fimasartan and placebo. The secondary end point was the overall efficacy and safety of low-dose fimasartan compared with that of placebo or valsartan. At week 8, SiDBP changed by -9.93 (8.86) mm Hg in the fimasartan group and by -2.08 (9.47) mm Hg in the placebo group, which indicated significant antihypertensive efficacy (P < 0.0001). Efficacy was shown at week 4 as measured by SiDBP (-9.96 [7.73] vs -2.27 [7.85] mm Hg; P < 0.0001) or sitting systolic blood pressure (SiSBP) (-16.18 [14.44] vs -1.95 [13.48] mmHg; P < 0.0001) and at week 8 as determined by SiSBP (-15.35 [16.63] vs -2.30 [14.91] mm Hg; P < 0.0001). The fimasartan group exhibited more potent antihypertensive efficacy than the valsartan group both at week 4 (SiDBP, -9.96 [7.73] vs -6.53 [9.58] mm Hg [P = 0.0123]; SiSBP, -16.18 [14.4] vs -7.65 [12.89] mm Hg [P = 0.0002]) and at week 8 (SiDBP, -9.93 [8.86] vs -5.47 [8.96] mm Hg [P = 0.0021]; SiSBP, -15.35 [16.63] vs -7.49 [13.68] mm Hg [P = 0.0021]). Most treatment-emergent adverse events (TEAEs) were mild (89 of 95), and there were no serious TEAEs. The incidence of TEAEs was 19.1% in the fimasartan group, 22.6% in the placebo group, and 13.6% in the valsartan group, with no significant differences. Low-dose fimasartan (30 mg) was well tolerated during the study period with no significant TEAEs. Low-dose fimasartan had an effective blood pressure-lowering effect that was greater than that of 80-mg valsartan in patients with mild to moderate hypertension. ClinicalTrials.gov identifier: NCT01672476.

Youn JC ，Ihm SH ，Bae JH ，Park SM ，Jeon DW ，Jung BC ，Park TH ，Lee NH ，Song JM ，Yoon YW ，Shin ES ，Sung KC ，Jung IH ，Pyun WB ，Joo SJ ，Park WJ ，Shin JH ，Kang SM ... -  《-》

24-Hour blood pressure response to lower dose (30 mg) fimasartan in Korean patients with mild to moderate essential hypertension.

Lee HY ，Kim CH ，Song JK ，Chae SC ，Jeong MH ，Kim DS ，Oh BH ... -  《-》

A Randomized, Multicenter, Double-blind, Placebo-controlled, 3 × 3 Factorial Design, Phase II Study to Evaluate the Efficacy and Safety of the Combination of Fimasartan/Amlodipine in Patients With Essential Hypertension.

The objective of this study was to evaluate the efficacy and safety of a fimasartan/amlodipine combination in patients with hypertension and to determine the optimal composition for a future single-pill combination formulation. This Phase II study was conducted by using a randomized, multicenter, double-blind, placebo-controlled, 3 × 3 factorial design. After a 2-week placebo run-in period, eligible hypertensive patients (with a sitting diastolic blood pressure [SiDBP] between 90 and 114 mm Hg) were randomized to treatment. They received single or combined administration of fimasartan at 3 doses (0, 30, and 60 mg) and amlodipine at 3 doses (0, 5, and 10 mg) for 8 weeks. The primary efficacy end point was the change in SiDBP from baseline and at week 8; secondary end points included the change in SiDBP from baseline and at week 4 and the changes in sitting systolic blood pressure from baseline and at weeks 4 and 8. Treatment-emergent adverse events (AEs) were also assessed. 420 Korean patients with mild to moderate hypertension were randomly allocated to the 9 groups. Mean (SD) SiDBP changes in each group after 8 weeks were as follows: placebo, -6.0 (8.5) mm Hg; amlodipine 5 mg, -10.6 (9.2) mm Hg; amlodipine 10 mg, -15.9 (7.2) mm Hg; fimasartan 30 mg, -10.1 (9.1) mm Hg; fimasartan 60 mg, -13.0 (10.0) mm Hg; fimasartan 30 mg/amlodipine 5 mg, -16.2 (8.5) mm Hg; fimasartan 30 mg/amlodipine 10 mg, -19.5 (7.5) mm Hg; fimasartan 60 mg/amlodipine 5 mg, -16.6 (6.9) mm Hg; and fimasartan 60 mg/amlodipine 10 mg, -21.5 (8.3) mm Hg. All treatment groups produced significantly greater reductions in blood pressure compared with the placebo group. In addition, all combination treatment groups had superior reductions in blood pressure compared with the monotherapy groups. In the combination treatment groups, doubling fimasartan dose in the given dose of amlodipine did not show further BP reduction, whereas doubling amlodipine dose showed significantly further BP reduction in the given dose of fimasartan. During the study period, 75 (17.9%) of 419 patients experienced 110 AEs. Ninety-five AEs were mild, 9 were moderate, and 6 were severe in intensity. Eight patients discontinued the study due to AEs. There was no significant difference in incidence of AEs among groups (P = 0.0884). The most common AE was headache (12 patients [2.9%]), followed by dizziness (11 patients [2.6%]) and elevated blood creatine phosphokinase levels (6 patients [1.4%]). Fimasartan combined with amlodipine produced superior blood pressure reductions and low levels of AEs compared with either monotherapy. Therefore, a single-pill combination with fimasartan 60 mg/amlodipine 10 mg will be developed. ClinicalTrials.gov: NCT01518998.

Lee HY ，Kim YJ ，Ahn T ，Youn HJ ，Chull Chae S ，Seog Seo H ，Kim KS ，Rhee MY ，Choi DJ ，Kim JJ ，Chun KJ ，Yoo BS ，Park JS ，Oh SK ，Kim DS ，Kwan J ，Ahn Y ，Bae Park J ，Jeong JO ，Hyon MS ，Cho EJ ，Han KR ，Kim DI ，Joo SJ ，Shin JH ，Sung KC ，Jeon ES ... -  《-》