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
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Essential Hypertension
- Sponsor
- Boryung Pharmaceutical Co., Ltd
- Enrollment
- 81
- Primary Endpoint
- the level of sitting diastolic blood pressure reduction
- Status
- Completed
- Last Updated
- 16 years ago
Overview
Brief Summary
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.
Detailed Description
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
Investigators
Eligibility Criteria
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
Arms & Interventions
Placebo
Placebo, 3 tablets
Intervention: Placebo
BR-A-657•K 20 mg group
Fimasartan 20 mg, 1 tablet + placebo, 2 tablets
Intervention: Fimasartan (BR-A-657•K) 20 mg
BR-A-657•K 60 mg group
Fimasartan 20 mg, 1 tablet + 40 mg, 1 tablet + placebo 1 tablet
Intervention: Fimasartan (BR-A-657•K) 60 mg
BR-A-657•K 180 mg group
Fimasartan 20 mg, 1 tablet + 80 mg, 1 tablet + 80 mg 1 tablet
Intervention: Fimasartan (BR-A-657•K) 180 mg
Outcomes
Primary Outcomes
the level of sitting diastolic blood pressure reduction
Time Frame: Day -1 vs Day 27
Secondary Outcomes
- 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)