Efficacy, Safety and Pharmacodynamic/Pharmacokinetic Study of Fimasartan (BR-A-657•K)

Fimasartan (BR-A-657-K), a selective blocker of AT1 receptor subtype, showed the rapid and potent antihypertensive effect in many hypertensive models. Phase I study, Fimasartan (BR-A-657-K) 20mg ~ 480mg single dosing with healthy subjects, demonstrated that the Fimasartan (BR-A-657-K) was very safe and well tolerated. Another phase I study, Fimasartan (BR-A-657-K) 120mg and 360mg dosing for 7 days, also showed that Fimasartan (BR-A-657-K) was safe and tolerable though one temporal adverse event was observed in high dose.

A randomized, double-blind, placebo-controlled, parallel grouped, clinical study will be conducted to evaluate the antihypertensive efficacy and tolerability and to determine adequate antihypertensive dosage of Fimasartan(BR-A-657-K) in patients with mild to moderate essential hypertension.

Approximately 60 patients will be enrolled over 12 months in Seoul National University Hospital.

After 2 weeks of placebo run-in period, all subjects will be randomized into one of the following 5 groups. Subjects will take test drug/placebo for 28 days of treatment period. If subjects take any antihypertensive medications before screening, the subjects will have 1 week of wash-out period.

Group I : Placebo, Group II : Fimasartan 20 mg, Group III: Fimasartan 60 mg, Group IV : Fimasartan 180 mg

Inclusion criteria

• Adult men and women, aged 18 - 65
• Patients with mild to moderate essential hypertension: On both screening and Day -1 visit, mean sitting DBP should be ≥ 95mmHg and ≤ 114mmHg, and ΔDBP on Day -14 and Day -1 should be within 7 mmHg
• Patients who gave their consent to participate in this study and signed the written informed consent form
• Patients who have understood the study, and been judged to be cooperative and able to participate in the study until the study completion date

Exclusion criteria

• Women of childbearing potential who have not received the hysterectomy or men who are not willing to use birth control measures.
• Patients whose sitting DBP is < 95mmHg or ≥ 115mmHg. Patients with severe hypertension whose SBP is ≥200mmHg
• Patients with secondary hypertension
• Patients with severe renal disease, gastrointestinal disorder, hematologic disorder, liver disease, etc. that can affect the absorption, distribution, metabolism and excretion of drugs
• Patients with symptoms of orthostatic hypotension
• Patients with severe insulin dependent diabetes or uncontrolled diabetes
• Patients who suffered myocardial infarction or serious coronary arterial disease over the past 6 months or patients with clinically significant congestive heart failure or valvular heart disease
• Patients with consumption disease, autoimmune disease, or connective tissue disease
• Patients with the history of type B hepatitis or type C hepatitis
• Patients with HIV infection or hepatitis
• Patients with clinically significant abnormal laboratory test findings
• Patients on any drug treatment that might affect the blood pressure
• Patients with allergy or contraindication to angiotensin II-receptor antagonists
• Patients with current or suspected alcohol addiction or history of drug abuse
• Patients whose mean weight lies out of the range of -15% ~ +35%, based on the Modified Metropolitan Life Insurance table
• Patients who are not eligible as subjects of the study, as determined by the principal investigator or a sub-investigator