Randomized, Double Blind, Placebo Controlled, Parallel Group Study to Evaluate the Antihypertensive Efficacy, Safety, Tolerability, and Pharmacodynamic/Pharmacokinetic Profiles After 4 Weeks of Oral Administration of Fimasartan(BR-A-657) at 20-180mg in Patients With Essential Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 81
- 主要终点
- the level of sitting diastolic blood pressure reduction
研究概览
简要总结
Study objective:
- To evaluate the antihypertensive efficacy, safety and tolerability of the drug after the oral administration of BR-A-657•K at 20~180mg for 4 weeks to patients with essential hypertension.
- To review the pharmacokinetic profile after the multiple administration and the pharmacodynamic profile regarding the renin-angiotensin system, after the oral administration of BR-A-657•K at 20~180mg for 4 weeks to patients with essential hypertension.
- To determine the dose for the clinical study at the next phase by analyzing the relationship between the antihypertensive efficacy and pharmacokinetic • pharmacodynamic results.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Placebo
Placebo, 3 tablets
干预措施: Placebo (Drug)
BR-A-657•K 20 mg group
Fimasartan 20 mg, 1 tablet + placebo, 2 tablets
干预措施: Fimasartan (BR-A-657•K) 20 mg (Drug)
BR-A-657•K 60 mg group
Fimasartan 20 mg, 1 tablet + 40 mg, 1 tablet + placebo 1 tablet
干预措施: Fimasartan (BR-A-657•K) 60 mg (Drug)
BR-A-657•K 180 mg group
Fimasartan 20 mg, 1 tablet + 80 mg, 1 tablet + 80 mg 1 tablet
干预措施: Fimasartan (BR-A-657•K) 180 mg (Drug)
结局指标
主要结局
the level of sitting diastolic blood pressure reduction
时间窗: Day -1 vs Day 27
次要结局
- the level of sitting systolic blood pressure reduction, mean blood pressure (MBP), 24-hr day-time, night-time SBP and DBP, T/P ratio based on the 24-hr Ambulatory Blood Pressure Monitoring(Day -1 vs Day 27)