fimasartan and Headache

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.

Topics: Adult; Aged; Amlodipine; Antihypertensive Agents; Biphenyl Compounds; Blood Pressure; Double-Blind Method; Essential Hypertension; Female; Headache; Humans; Hypertension; Male; Middle Aged; Pyrimidines; Tetrazoles

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.

Topics: Adult; Aged; Antihypertensive Agents; Biphenyl Compounds; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Double-Blind Method; Drug Administration Schedule; Essential Hypertension; Female; Headache; Humans; Hypertension; Korea; Male; Middle Aged; Pyrimidines; Republic of Korea; Tetrazoles; Valine; Valsartan; Young Adult

Angiotensin II receptor blockers (ARBs) play a key role in hypertension therapy. Recently, fimasartan, the ninth ARB, was developed, but its safety and efficacy have not been well established.. The objective of this study was to determine whether age, sex, concomitant disease, and current antihypertensive medications affect the safety and efficacy of fimasartan in patients with arterial hypertension.. This was a large-scale, open-label observational study to determine the safety and efficacy of fimasartan in patients with hypertension. Patients who were treated for more than 2 months with fimasartan (60 or 120 mg, once daily) were recruited, and the data were systematically collected using electronic case report forms. Written informed consent forms were obtained from all patients.. A total of 14,151 patients (50.7 % males; mean age 59 ± 12 years) were evaluated, of whom 37.9 % were never treated with fimasartan, 53.5 % were switched to fimasartan, and 8.5 % had fimasartan added to their treatment. Overall, fimasartan reduced systolic blood pressure (SBP) from 145.4 ± 18.1 to 126.8 ± 12.6 mmHg and diastolic blood pressure (DBP) from 88.7 ± 11.8 to 79.0 ± 8.7 mmHg (all p < 0.001). The pulse rate decreased from 74.4 ± 10.3 to 71.9 ± 9.2 beats/min in comparison with before treatment (p < 0.001). The reductions were similar between sexes, age groups, and patients with and without co-morbidities, and were not dependent on prior or concomitant treatment with other antihypertensive drugs. Adverse events were reported in 3.31 % (treatment-emergent) and 2.35 % (drug-related) of patients; there were no dose differences for adverse events. The most frequent adverse events were dizziness (1.55 %) and headache (0.52 %); other adverse events were rare. The responder rate (DBP to <90 mmHg or a reduction of ≥10 mmHg) and the goal rate (combined SBP/DBP <140/90 mmHg) were 85.0 and 75.6 %, respectively. Global drug compliance was rated as excellent, very good, good, and poor in 68.1, 26.9, 3.4, and 1.7 % of patients, respectively.. The safety, efficacy, and compliance of fimasartan were found to be excellent in a large patient population that included patients potentially at higher risk for adverse events.

Topics: Adult; Aged; Angiotensin Receptor Antagonists; Antihypertensive Agents; Biphenyl Compounds; Blood Pressure; Dizziness; Female; Headache; Humans; Hypertension; Male; Middle Aged; Pyrimidines; Tetrazoles; Treatment Outcome