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

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

Study objective:

1. 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.
2. 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.
3. To determine the dose for the clinical study at the next phase by analyzing the relationship between the antihypertensive efficacy and pharmacokinetic • pharmacodynamic results.

Study Overview

• Status: Completed
• Conditions: Essential Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: Fimasartan (BR-A-657•K) 20 mg; Drug: Fimasartan (BR-A-657•K) 60 mg; Drug: Fimasartan (BR-A-657•K) 180 mg

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

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

1. Women of childbearing potential who have not received the hysterectomy or men who are not willing to use birth control measures.
2. Patients whose sitting DBP is < 95mmHg or ≥ 115mmHg. Patients with severe hypertension whose SBP is ≥200mmHg
3. Patients with secondary hypertension
4. Patients with severe renal disease, gastrointestinal disorder, hematologic disorder, liver disease, etc. that can affect the absorption, distribution, metabolism and excretion of drugs
5. Patients with symptoms of orthostatic hypotension
6. Patients with severe insulin dependent diabetes or uncontrolled diabetes
7. 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
8. Patients with consumption disease, autoimmune disease, or connective tissue disease
9. Patients with the history of type B hepatitis or type C hepatitis
10. Patients with HIV infection or hepatitis
11. Patients with clinically significant abnormal laboratory test findings
12. Patients on any drug treatment that might affect the blood pressure
13. Patients with allergy or contraindication to angiotensin II-receptor antagonists
14. Patients with current or suspected alcohol addiction or history of drug abuse
15. Patients whose mean weight lies out of the range of -15% ~ +35%, based on the Modified Metropolitan Life Insurance table
16. Patients who are not eligible as subjects of the study, as determined by the principal investigator or a sub-investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo, 3 tablets	Drug: Placebo; Placebo
Active Comparator: BR-A-657•K 20 mg group; Fimasartan 20 mg, 1 tablet + placebo, 2 tablets	Drug: Fimasartan (BR-A-657•K) 20 mg; Fimasartan 20 mg, 1 tablet + placebo, 2 tablets; Other Names: Fimasartan
Active Comparator: BR-A-657•K 60 mg group; Fimasartan 20 mg, 1 tablet + 40 mg, 1 tablet + placebo 1 tablet	Drug: Fimasartan (BR-A-657•K) 60 mg; Fimasartan 20 mg, 1 tablet + 40 mg, 1 tablet + placebo 1 tablet; Other Names: Fimasartan
Active Comparator: BR-A-657•K 180 mg group; Fimasartan 20 mg, 1 tablet + 80 mg, 1 tablet + 80 mg 1 tablet	Drug: Fimasartan (BR-A-657•K) 180 mg; Fimasartan 20 mg, 1 tablet + 80 mg, 1 tablet + 80 mg 1 tablet; Other Names: Fimasartan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the level of sitting diastolic blood pressure reduction	Day -1 vs Day 27

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Boryung Pharmaceutical Co., Ltd

Publications and helpful links

General Publications

• Lee H, Yang HM, Lee HY, Kim JJ, Choi DJ, Seung KB, Jeon ES, Ha JW, Rim SJ, Park JB, Shin JH, Oh BH. Efficacy and tolerability of once-daily oral fimasartan 20 to 240 mg/d in Korean Patients with hypertension: findings from Two Phase II, randomized, double-blind, placebo-controlled studies. Clin Ther. 2012 Jun;34(6):1273-89. doi: 10.1016/j.clinthera.2012.04.021. Epub 2012 May 17. Erratum In: Clin Ther. 2012 Sep;34(9):2020.

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): June 1, 2006
• Study Completion (Actual): June 1, 2006

Study Registration Dates

• First Submitted: July 10, 2009
• First Submitted That Met QC Criteria: July 10, 2009
• First Posted (Estimate): July 13, 2009

Study Record Updates

• Last Update Posted (Estimate): July 13, 2009
• Last Update Submitted That Met QC Criteria: July 10, 2009
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: Essential Hypertension; Fimasartan
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension
• Other Study ID Numbers: A657-BR-CT-201