Hypertension
Conditions
Keywords
Hypertension, Losartan
Brief summary
The purpose of this study is to evaluate the antihypertensive efficacy and safety of Fimasartan (BR-A-657•K) 60 mg\ 120 mg in patients with mild to moderate essential hypertension.
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, Losartan-controlled, Parallel Group Comparison Dose Titration Clinical Study to Evaluate the Antihypertensive Efficacy and Safety of Fimasartan (BR-A-657•K) 60mg\ 120mg in Patients with Mild to Moderate Essential Hypertension. Approximately 480 patients will be enrolled over 12 months in 24 centers nationwide. After 2 weeks of placebo run-in period, all subjects will be randomized into one of the following 2 groups. Subjects will take test/control drug for 12 weeks of treatment period. And Extensin study have 12 weeks in treatment period. If subjects take any antihypertensive medications before screening, the subjects will have 1 week of wash-out period. If the hypertension is not controlled well, there is a possibility of dose titration. Group I : Fimasartan group. Group II : Losartan group
Interventions
DRUGFimasartan
Fimasartan 60 \ 120mg/po take one tablets once a day
Losartan 50 mg \ 100 mg/po, take one tablets once a day
Sponsors
Seoul National University Hospital
The Catholic University of Korea
Kangbuk Samsung Hospital
Konkuk University Medical Center
Konyang University Hospital
Keimyung University
Korea University
Korea University Guro Hospital
Dongguk University International Hospital
Seoul National University Bundang Hospital
Samsung Medical Center
Asan Medical Center
Severance Hospital
Ajou University
Wonju Severance Christian Hospital
Yeungnam University Hospital
Yonsei University
Inha University Hospital
Chonbuk National University Hospital
Cheil General Hospital and Women's Healthcare Center
Chungnam National University
Chungbuk National University Hospital
Hanyang University
Boryung Pharmaceutical Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Mild to moderate essential hypertension : sitting diastolic blood pressure measured at Placebo visit and Baseline are 90\ 109mmHg inclusive and the difference between sitting diastolic blood pressures measured at Placebo visit and Baseline(Day0) 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 89mmHg or more than 110mmHg 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 12weeks, 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(include carrier) * 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 participated other clinical trial 12 weeks before Screening Patients judged to be inappropriate for this study by the investigator with other reasons
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diastolic Blood Pressure Change | baseline and 12 weeks | Value of DBP at 12 Weeks minus value of DBP at Baseline while in a sitting position |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Diastolic Blood Pressure Change | baseline and 4 weeks, 8 weeks | * Value of DBP at 4 Weeks minus value of DBP at Baseline while in a sitting position * Value of DBP at 8 Weeks minus value of DBP at Baseline while in a sitting position |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control: Losartan Losartan group
Losartan (Control): Losartan 50 mg \
100 mg/po, take one tablets once a day | 238 |
| Test: Fimasartan Fimasartan 60mg, 120mg
Fimasartan: Fimasartan 60 \
120mg/po take one tablets once a day | 247 |
| Total | 485 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Extension Study | Adverse Event | 1 | 1 |
| Extension Study | Others | 0 | 1 |
| Extension Study | Protocol Violation | 3 | 0 |
| Extension Study | Withdrawal by Subject | 1 | 1 |
| Main Study | Adverse Event | 6 | 7 |
| Main Study | Lack of Efficacy | 3 | 0 |
| Main Study | Lost to Follow-up | 5 | 0 |
| Main Study | Physician Decision | 0 | 1 |
| Main Study | Protocol Violation | 3 | 6 |
| Main Study | Withdrawal by Subject | 20 | 15 |
Baseline characteristics
| Characteristic | Control: Losartan | Test: Fimasartan | Total |
|---|---|---|---|
| Age, Continuous | 53.58 years STANDARD_DEVIATION 9.61 | 53.96 years STANDARD_DEVIATION 8.79 | 53.77 years STANDARD_DEVIATION 9.19 |
| Sex: Female, Male Female | 71 Participants | 79 Participants | 150 Participants |
| Sex: Female, Male Male | 167 Participants | 168 Participants | 335 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 76 / 250 | 82 / 255 |
| serious Total, serious adverse events | 5 / 250 | 3 / 255 |
Outcome results
Primary
Diastolic Blood Pressure Change
Value of DBP at 12 Weeks minus value of DBP at Baseline while in a sitting position
Time frame: baseline and 12 weeks
Population: As ITT group, these are subjects who have been randomly assigned and have at least one primary end point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control: Losartan / Week 12 -ITT | Diastolic Blood Pressure Change | -8.56 mmHg | Standard Deviation 7.72 |
| Test: Fimasartan / Week 12 -ITT | Diastolic Blood Pressure Change | -11.26 mmHg | Standard Deviation 7.53 |
p-value: 0.0001t-test, 2 sided
Secondary
Diastolic Blood Pressure Change
* Value of DBP at 4 Weeks minus value of DBP at Baseline while in a sitting position * Value of DBP at 8 Weeks minus value of DBP at Baseline while in a sitting position
Time frame: baseline and 4 weeks, 8 weeks
Population: As ITT group, these are subjects who have been randomly assigned and have at least one primary end point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control: Losartan / Week 12 -ITT | Diastolic Blood Pressure Change | Week 4 | -5.73 mmHg | Standard Deviation 6.56 |
| Control: Losartan / Week 12 -ITT | Diastolic Blood Pressure Change | Week 8 | -8.01 mmHg | Standard Deviation 7.16 |
| Test: Fimasartan / Week 12 -ITT | Diastolic Blood Pressure Change | Week 4 | -8.22 mmHg | Standard Deviation 7.35 |
| Test: Fimasartan / Week 12 -ITT | Diastolic Blood Pressure Change | Week 8 | -11.01 mmHg | Standard Deviation 7.63 |
p-value: 0.0001t-test, 2 sided