Antihypertensive Efficacy and Tolerability and Determine the Adequate Antihypertensive Dosage of Fimasartan in Mild to Moderate Essential Hypertension Patients

A Randomized, Double-Blind, Placebo-Controlled, Parallel Grouped, Clinical Study to Evaluate the Antihypertensive Efficacy and Tolerability and to Determine the Adequate Antihypertensive Dosage of Fimasartan(BR-A-657-K) in Patients With Mild to Moderate Essential Hypertension

The purpose of this study is to evaluate the antihypertensive efficacy and tolerability of 8 week treatment with Fimasartan (BR-A-657-K) 20, 60, 120, 240 mg and placebo in patients with mild to moderate essential hypertension and to determine the adequate antihypertensive dosage for later clinical study.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Fimasartan

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 182 patients will be enrolled over 12 months in 8 centers nationwide.

After 2 weeks of placebo run-in period, all subjects will be randomized into one of the following 5 groups. Subjects will take test/control drug for 8 weeks 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 120 mg, Group V : Fimasartan 240 mg,

• Study Type: Interventional
• Enrollment (Anticipated): 182
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Mild to moderate essential hypertension : sitting diastolic blood pressure measured at Screening and Baseline(Day1) are 95~114 mmHg inclusive and the difference between sitting diastolic blood pressures measured at Day -14 and Baseline(Day1) is under 7mmHg.
• Subjects who agree to participate in this sudy and give written informed consent
• Subjects considered to understand the study, be cooperative, and able to be followed-up until the end of the study

Exclusion Criteria:

• The sitting DBP is less than 94mmHg or more than 115mmHg or severe hypertensive patient with sitting systolic blood pressure over 200mmHg
• Patients with secondary hypertension
• Patients with severe renal(Creatinine more 1.5 times than upper limit of normal), gastrointestinal, hematological or hepatic(AST, ALT more 2 twice more than upper limit of normal)disease etc. which might affect absorption, disposition, metabolism or excretion of the drug
• Patients with postural hypotension
• Patients with sever insulin dependent diabetes mellitus or uncontrolled diabetes mellitus(HbA1c>9%, regimen change of oral hypoglycemic agents within 3 months, treated insulin before screening)
• Patients with a history of myocardial infarction, severe coronary artery disease or clinically significant heart failure or valvular defect in last 6 months
• Patients with consumptive disease, autoimmune disease, connective tissue disease
• Patients with a history of type B or C hepatitis
• Patients with HIV or hepatitis
• Patients with clinically significant laboratory abnormality
• Patients receiving any drugs known to affect blood pressure or medical treatments that can influence the blood pressure
• Patients with allergy or contraindication to any angiotensin II receptor antagonists
• Female of childbearing potential who does not undergo hysterectomy or is not post-menopausal
• Patients judged to have a history of alcohol or drug abuse by the investigator
• Patients with average weight > +35% or <-15% in Modified Metropolitan Life Insurance table
• Patients participated other clinical trial 3 months before Screening
• Patients judged to be inappropriate for this study by the investigator with other reasons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; 3 tablets of placebo will be taken 30minutes after breakfast for 8 weeks	Drug: Fimasartan
ACTIVE_COMPARATOR: Fimasartan 20mg; 2 tablets of placebo and 1 tablets of fimasartan 20mg will be taken 30minutes after breakfast for 8 weeks	Drug: Fimasartan
ACTIVE_COMPARATOR: Fimasartan 60mg; 3 tablets of fimasartan 20mg will be taken 30minutes after breakfast for 8 weeks	Drug: Fimasartan
ACTIVE_COMPARATOR: Fimasartan 120mg; 3 tablets of fimasartan 40mg will be taken 30minutes after breakfast	Drug: Fimasartan
ACTIVE_COMPARATOR: Fimasartan 240mg; 3 tablets of fimasartan 80mg will be taken 30minutes after breakfast for 8 weeks	Drug: Fimasartan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
change from baseline to end of 8 week treatment in sitting diastolic blood pressure	8 week from baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
change from baseline to end of 2,4 week treatment in sitting diastolic blood pressure	2, 4 week from baseline
change from baseline to end of 2,4,8 week treatment in sitting systolic blood pressure	2,4,8 week from baseline
responders after end of 8 week treatment(portion of DBP<90mmHg or the difference from baseline and end of 8 week treatment>10mmHg	8 week from baseline

Collaborators and Investigators

• Sponsor: Boryung Pharmaceutical Co., Ltd
• Collaborators: Samsung Medical Center; Asan Medical Center; Seoul National University Hospital; Seoul National University Bundang Hospital; Cheil General Hospital and Women's Healthcare Center; Yonsei University; The Catholic University of Korea; Severance Hospital
• Investigators: Study Chair: Byung-Hee Oh, Professor, Seoul National University Hospital; Principal Investigator: Jae-Joong Kim, Professor, Asan Medical Center; Principal Investigator: Eun-Suk Jeon, Professor, Samsung Medical Center; Principal Investigator: Ki-Bae Seong, Professor, Kangnam St.Mary's Hospital; Principal Investigator: Jong-Won Ha, Professor, Severance Hospital; Principal Investigator: Se-Joong Lim, Professor, Yonsei University; Principal Investigator: Jeong-Bae Park, Professor, Cheil General Hospital and Women's Healthcare Center

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: September 1, 2007
• Primary Completion (ACTUAL): June 1, 2008
• Study Completion (ACTUAL): June 1, 2008

Study Registration Dates

• First Submitted: June 16, 2009
• First Submitted That Met QC Criteria: June 17, 2009
• First Posted (ESTIMATE): June 18, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): June 18, 2009
• Last Update Submitted That Met QC Criteria: June 17, 2009
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Keywords: Hypertension; Fimasartan
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Essential Hypertension
• Other Study ID Numbers: A-657-BR-CT-202