Clinical trial NCT00923611: Antihypertensive Efficacy and Tolerability and Determine the Adequate Antihypertensive Dosage of Fimasartan in Mild to Moderate Essential Hypertension Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertension
Keywords: Hypertension
Fimasartan
Lead sponsor: Boryung Pharmaceutical Co., Ltd
Sponsor class: INDUSTRY
Collaborators: name: Seoul National University Hospital
name: Samsung Medical Center
name: Asan Medical Center
name: Seoul National University Bundang Hospital
name: The Catholic University of Korea
name: Severance Hospital
name: Yonsei University
name: Cheil General Hospital and Women's Healthcare Center
First posted: 2009-06-18
Enrollment: 182
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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,

Eligibility criteria: 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

Primary outcomes:
measure: change from baseline to end of 8 week treatment in sitting diastolic blood pressure
timeFrame: 8 week from baseline
Secondary outcomes:
measure: change from baseline to end of 2,4 week treatment in sitting diastolic blood pressure
timeFrame: 2, 4 week from baseline
measure: change from baseline to end of 2,4,8 week treatment in sitting systolic blood pressure
timeFrame: 2,4,8 week from baseline
measure: responders after end of 8 week treatment(portion of DBP<90mmHg or the difference from baseline and end of 8 week treatment>10mmHg
timeFrame: 8 week from baseline
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hospital
name: Byung-Hee Oh, Professor
role: STUDY_CHAIR
affiliation: Asan Medical Center
name: Jae-Joong Kim, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Samsung Medical Center
name: Eun-Suk Jeon, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Seoul National University Bundang Hospital
name: Dong-Ju Choi, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Kangnam ST.Mary's Hospital
name: Ki-Bae Seong, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Severance Hospital
name: Jong-Won Ha, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Yonsei University
name: Se-Joong Lim, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Cheil General Hospital and Women's Healthcare Center
name: Jeong-Bae Park, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.