A Randomized, Double-blind, Multicenter, Phase III Study to Evaluate the Efficacy and Safety of Combination of Fimasartan/Rosuvastatin in Comparison to Each Component Administered Alone in Patients With Essential Hypertension and Dyslipidemia
Primary Purpose
Essential Hypertension, Dyslipidemia
Status
Completed
Phase
Phase 3
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Fimasartan and Rosuvastatin
Fimasartan
Rosuvastatin
Sponsored by
About this trial
This is an interventional treatment trial for Essential Hypertension, Dyslipidemia
Eligibility Criteria
Inclusion Criteria:
- Patients who voluntarily signed informed consent for participating in this clinical trial
- Male and female between 20 and 75 years old
- Patients must have been confirmed essential hypertension and dyslipidemia at Screening visit (Visit1)
Patients who meet the following criteria of fasting LDL-C and blood pressure at Baseline visit (Visit3) assessment after undergoing the therapeutic lifestyle change.
- Low risk group: the case that does not have any other risk factor apart from hypertension / LDL-C (mg/dL): ≥160, ≤250, Mean SiSBP(mmHg): ≥140, <180
- Moderate risk group: the case that has more than or equal to one risk factor apart from hypertension and has the 10-year risk of less than 10% / LDL-C (mg/dL): ≥160, ≤250, Mean SiSBP(mmHg): ≥140, <180
- Moderate high risk group: the case that has more than or equal to one risk factor apart from hypertension and has the 10-year risk between 10% and 20% / LDL-C (mg/dL): ≥130, ≤250, Mean SiSBP(mmHg): ≥140, <180
High risk group: the case of CHD (Coronary heart disease) or CHD risk equivalents
- Risk factors include cigarette smoking, hypertension (BP≥140/90 mmHg or on antihypertensive medication), low HDL cholesterol (<40mg/dL), family history of premature CHD(CHD in male first-degree relative <55 years of age; CHD in female first-degree relative < 65 years of age), and age (men≥45 years; women ≥55 years). in case of HDL-C ≥60mg/dL, reduce 1 from the total number of risk factors.
- Electronic 10 year risk calculators are available at www.nhlbi.nih.gov/guidelines/cholesterol
- CHD includes history of myocardial infarction, unstable angina, coronary artery procedures (angioplasty or bypass surgery), or evidence of clinically significant myocardial ischemia.
- CHD risk equivalents include atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm and carotid artery disease [transient ischemic attacks or stroke of carotid origin or >50% obstruction of a carotid artery]), diabetes and 2+ risk factors with 10 year risk of over 20%
- Subject must be able to understand the trial procedures and be willing to cooperate and complete the trial.
Exclusion Criteria:
- Severe hypertension patients with mean siSBP ≥ 180mmHg and/or SiDBP ≥110mmHg at the assessment of Screening visit (Visit1) and/or Baseline visit (Visit3). Or patients with postural hypotension with manifestation.
- Patients with the mean SiSBP from 3 times of measurement of over 20mmHg.
- Secondary hypertension patients, but not limited to the following disease (example: renovascular disease, adrenal medullary and cortical hyperfunctions, coarctation of the aorta, hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing's syndrome, pheochromocytoma, polycystic kidney disease, etc)
- Secondary dyslipidemia: nephrotic syndrome, dysproteinemia, obstructive hepatopathy or Cushing's syndrome.
- Patients with fasting TG ≥ 400mg/dL at Pre-Baseline visit (Visit2) assessment
- History of myopathy, rhabdomyolysis or/and CK ≥ 2 times upper normal limit.
- Use of lipid modifying drug within 4 weeks prior to Pre-Baseline visit (Visit2) and/or antihypertensive drug within 2 weeks prior to Pre-Baseline visit(Visit2)
- Clinically significant renal function abnormality in the laboratory results at Pre-Baseline visit (i.e. serum creatinine ≥ 1.5 times upper normal limit), liver function abnormality (ALT, AST ≥ 2 times upper normal limit), severe fatty liver disease that requires medication.
- Clinically significant hypokalemia(less than 3.5 mmol/L) or hyperkalemia (exceeded 5.5 mmol/L) measured at Pre-Baseline visit (Visit2)
- Subjects with following surgical and internal disease that may affect absorption, distribution, metabolism or excretion of drugs and have conditions which include the following (but are not limited to): history of major gastrointestinal surgeries including gastrectomy, gastro-enterostomy or bowel resection, gastrointestinal bypass graft and stabling; current active gastritis, ulcer, gastrointestinal and rectal bleeding, presence of active inflammatory bowel syndrome or biliary obstruction with the past 12 months.
- Subjects with depletion of body fluid or sodium ion not able to correct
- Subjects with sever insulin-dependent Diabetes Mellitus(DM) or Chronic DM (HbA1c > 9% at Pre-Baseline visit, dosage of an oral hypoglycemic agent was modified within 12 weeks prior to screening visit , or currently use of active insulin treatment) or with hypothyroidism not able to correct.( TSH ≥ 1.5 times upper normal limit)
- Subjects with severe heart disease (Heart failure New York Heart Association(NYHA) class 3 and 4), or history of any of the followings within the past 6 months; ischemic heart disease (e.g. angina pectoris, myocardial infarction), peripheral vascular disease, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft.
- Subjects with clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter or any other clinical significant arrhythmia conditions at discretion of investigator
- Subjects with hypertrophic obstructive cardiomyopathy, severe obstructive coronary artery disease, aortic stenosis, hemodynamically significant aortic valve stenosis, or mitral valve stenosis.
- Subjects with severe cerebrovascular disorder (e.g. stroke, cerebral infarction or cerebral hemorrhage within the past 6 months)
- Subjects with chronic inflammatory disease requiring an chronic anti-inflammatory therapy, past or current medical history with wasting disease, autoimmune diseases (e.g. rheumatoid arthritis, systemic lupus erythematosus) or connective tissue disease.
- Subjects with known moderate or malignant retinosis (e.g. retinal hemorrhage, visual disturbance or retinal microaneurysm in the past 6 months)
- Subjects with hepatitis B (including positive test for HBsAg), hepatitis C-positive
- Subjects with history or evidence of abusing drugs or alcohol within the past 2 years.
- Medical history with hypersensitivity to angiotensin II antagonist based drugs or HMG-CoA reductase inhibitor based drugs or any ingredient contained in these 2 drugs.
- Medical history with clinically significant hypersensitivity to any components or other drugs on the investigational product or additives (yellow 5)
- Subjects with hereditary disorders of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
- Pregnant women and lactating female.
- Subjects planning pregnancy or childbearing potential who are not using effective contraceptive methods (surgical sterilized, intrauterine (contraceptive) device/condom or the combination of diaphragm and spermicidal agents)
- Subjects who are participating in another trial or took other investigational product within 12 weeks prior to Screening visit
- Medical history of all kinds of malignant tumor including leukemia and lymphoma in the past 5 years
- A subject with other reasons not specified above that, ineligible to participate in this clinical trial at discretion of study investigators.
Sites / Locations
- Seoul university Bundang hospital
- Dong-A university hospital
- Inje Heaundai Paik hospital
- Inje university Busan Paik hospital
- ChungNam university hospital
- DanGuk university hospital
- The Catholic university of Korea Daegu hospital
- DongGuk university Gyeongju hospital
- DongGuk university Ilsan hospital
- Inje university Ilsan Paik hospital
- Gachon university Gil medical center
- Inha university hospital
- Jeju national university hospital
- JeonNam university hospital
- Kyungbook National university hospital
- Gangnam Severance hospital
- Jeil hospital
- Korea university Anam hospital
- Korea university Guro hospital
- Kyunghee university hospital
- Samsung Seoul hospital
- Seoul national university hospital
- Severance hospital
- The Catholic university St. Mary hospital
- Aju university hospital
- YoungNam university hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Active Comparator
Arm Label
Fimasartan and Rosuvastatin
Fimasartan
Rosuvastatin
Arm Description
Combination of Fimasartan and Rosuvastatin
Fimasartan monotherapy
Rosuvastatin monotherapy
Outcomes
Primary Outcome Measures
Change rate of LDL-C at week 8 of Fimasartan/Rosuvastatin combination administration from the Baseline to compare the one of Fimasartan 120mg single administration
Change of SiSBP at week 8 of Fimasartan/Rosuvastatin combination administration from the Baseline to compare the one of Rosuvastatin 20mg single administration
Secondary Outcome Measures
Full Information
NCT ID
NCT02166814
First Posted
June 16, 2014
Last Updated
February 9, 2017
Sponsor
Boryung Pharmaceutical Co., Ltd
1. Study Identification
Unique Protocol Identification Number
NCT02166814
Brief Title
A Randomized, Double-blind, Multicenter, Phase III Study to Evaluate the Efficacy and Safety of Combination of Fimasartan/Rosuvastatin in Comparison to Each Component Administered Alone in Patients With Essential Hypertension and Dyslipidemia
Study Type
Interventional
2. Study Status
Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
August 2014 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
September 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boryung Pharmaceutical Co., Ltd
4. Oversight
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of combination of Fimasartan/Rosuvastatin in comparison to each component administered alone in patients with essential hypertension and dyslipidemia.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Essential Hypertension, Dyslipidemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
140 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fimasartan and Rosuvastatin
Arm Type
Experimental
Arm Description
Combination of Fimasartan and Rosuvastatin
Arm Title
Fimasartan
Arm Type
Active Comparator
Arm Description
Fimasartan monotherapy
Arm Title
Rosuvastatin
Arm Type
Active Comparator
Arm Description
Rosuvastatin monotherapy
Intervention Type
Drug
Intervention Name(s)
Fimasartan and Rosuvastatin
Intervention Type
Drug
Intervention Name(s)
Fimasartan
Intervention Type
Drug
Intervention Name(s)
Rosuvastatin
Primary Outcome Measure Information:
Title
Change rate of LDL-C at week 8 of Fimasartan/Rosuvastatin combination administration from the Baseline to compare the one of Fimasartan 120mg single administration
Time Frame
8 weeks from Baseline Visit
Title
Change of SiSBP at week 8 of Fimasartan/Rosuvastatin combination administration from the Baseline to compare the one of Rosuvastatin 20mg single administration
Time Frame
8 weeks from Baseline Visit
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients who voluntarily signed informed consent for participating in this clinical trial
Male and female between 20 and 75 years old
Patients must have been confirmed essential hypertension and dyslipidemia at Screening visit (Visit1)
Patients who meet the following criteria of fasting LDL-C and blood pressure at Baseline visit (Visit3) assessment after undergoing the therapeutic lifestyle change.
Low risk group: the case that does not have any other risk factor apart from hypertension / LDL-C (mg/dL): ≥160, ≤250, Mean SiSBP(mmHg): ≥140, <180
Moderate risk group: the case that has more than or equal to one risk factor apart from hypertension and has the 10-year risk of less than 10% / LDL-C (mg/dL): ≥160, ≤250, Mean SiSBP(mmHg): ≥140, <180
Moderate high risk group: the case that has more than or equal to one risk factor apart from hypertension and has the 10-year risk between 10% and 20% / LDL-C (mg/dL): ≥130, ≤250, Mean SiSBP(mmHg): ≥140, <180
High risk group: the case of CHD (Coronary heart disease) or CHD risk equivalents
Risk factors include cigarette smoking, hypertension (BP≥140/90 mmHg or on antihypertensive medication), low HDL cholesterol (<40mg/dL), family history of premature CHD(CHD in male first-degree relative <55 years of age; CHD in female first-degree relative < 65 years of age), and age (men≥45 years; women ≥55 years). in case of HDL-C ≥60mg/dL, reduce 1 from the total number of risk factors.
Electronic 10 year risk calculators are available at www.nhlbi.nih.gov/guidelines/cholesterol
CHD includes history of myocardial infarction, unstable angina, coronary artery procedures (angioplasty or bypass surgery), or evidence of clinically significant myocardial ischemia.
CHD risk equivalents include atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm and carotid artery disease [transient ischemic attacks or stroke of carotid origin or >50% obstruction of a carotid artery]), diabetes and 2+ risk factors with 10 year risk of over 20%
Subject must be able to understand the trial procedures and be willing to cooperate and complete the trial.
Exclusion Criteria:
Severe hypertension patients with mean siSBP ≥ 180mmHg and/or SiDBP ≥110mmHg at the assessment of Screening visit (Visit1) and/or Baseline visit (Visit3). Or patients with postural hypotension with manifestation.
Patients with the mean SiSBP from 3 times of measurement of over 20mmHg.
Secondary hypertension patients, but not limited to the following disease (example: renovascular disease, adrenal medullary and cortical hyperfunctions, coarctation of the aorta, hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing's syndrome, pheochromocytoma, polycystic kidney disease, etc)
Secondary dyslipidemia: nephrotic syndrome, dysproteinemia, obstructive hepatopathy or Cushing's syndrome.
Patients with fasting TG ≥ 400mg/dL at Pre-Baseline visit (Visit2) assessment
History of myopathy, rhabdomyolysis or/and CK ≥ 2 times upper normal limit.
Use of lipid modifying drug within 4 weeks prior to Pre-Baseline visit (Visit2) and/or antihypertensive drug within 2 weeks prior to Pre-Baseline visit(Visit2)
Clinically significant renal function abnormality in the laboratory results at Pre-Baseline visit (i.e. serum creatinine ≥ 1.5 times upper normal limit), liver function abnormality (ALT, AST ≥ 2 times upper normal limit), severe fatty liver disease that requires medication.
Clinically significant hypokalemia(less than 3.5 mmol/L) or hyperkalemia (exceeded 5.5 mmol/L) measured at Pre-Baseline visit (Visit2)
Subjects with following surgical and internal disease that may affect absorption, distribution, metabolism or excretion of drugs and have conditions which include the following (but are not limited to): history of major gastrointestinal surgeries including gastrectomy, gastro-enterostomy or bowel resection, gastrointestinal bypass graft and stabling; current active gastritis, ulcer, gastrointestinal and rectal bleeding, presence of active inflammatory bowel syndrome or biliary obstruction with the past 12 months.
Subjects with depletion of body fluid or sodium ion not able to correct
Subjects with sever insulin-dependent Diabetes Mellitus(DM) or Chronic DM (HbA1c > 9% at Pre-Baseline visit, dosage of an oral hypoglycemic agent was modified within 12 weeks prior to screening visit , or currently use of active insulin treatment) or with hypothyroidism not able to correct.( TSH ≥ 1.5 times upper normal limit)
Subjects with severe heart disease (Heart failure New York Heart Association(NYHA) class 3 and 4), or history of any of the followings within the past 6 months; ischemic heart disease (e.g. angina pectoris, myocardial infarction), peripheral vascular disease, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft.
Subjects with clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter or any other clinical significant arrhythmia conditions at discretion of investigator
Subjects with hypertrophic obstructive cardiomyopathy, severe obstructive coronary artery disease, aortic stenosis, hemodynamically significant aortic valve stenosis, or mitral valve stenosis.
Subjects with severe cerebrovascular disorder (e.g. stroke, cerebral infarction or cerebral hemorrhage within the past 6 months)
Subjects with chronic inflammatory disease requiring an chronic anti-inflammatory therapy, past or current medical history with wasting disease, autoimmune diseases (e.g. rheumatoid arthritis, systemic lupus erythematosus) or connective tissue disease.
Subjects with known moderate or malignant retinosis (e.g. retinal hemorrhage, visual disturbance or retinal microaneurysm in the past 6 months)
Subjects with hepatitis B (including positive test for HBsAg), hepatitis C-positive
Subjects with history or evidence of abusing drugs or alcohol within the past 2 years.
Medical history with hypersensitivity to angiotensin II antagonist based drugs or HMG-CoA reductase inhibitor based drugs or any ingredient contained in these 2 drugs.
Medical history with clinically significant hypersensitivity to any components or other drugs on the investigational product or additives (yellow 5)
Subjects with hereditary disorders of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
Pregnant women and lactating female.
Subjects planning pregnancy or childbearing potential who are not using effective contraceptive methods (surgical sterilized, intrauterine (contraceptive) device/condom or the combination of diaphragm and spermicidal agents)
Subjects who are participating in another trial or took other investigational product within 12 weeks prior to Screening visit
Medical history of all kinds of malignant tumor including leukemia and lymphoma in the past 5 years
A subject with other reasons not specified above that, ineligible to participate in this clinical trial at discretion of study investigators.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dongjoo Oh
Organizational Affiliation
Korea University Guro Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Seoul university Bundang hospital
City
Bundang
Country
Korea, Republic of
Facility Name
Dong-A university hospital
City
Busan
Country
Korea, Republic of
Facility Name
Inje Heaundai Paik hospital
City
Busan
Country
Korea, Republic of
Facility Name
Inje university Busan Paik hospital
City
Busan
Country
Korea, Republic of
Facility Name
ChungNam university hospital
City
ChungNam
Country
Korea, Republic of
Facility Name
DanGuk university hospital
City
Chungnam
Country
Korea, Republic of
Facility Name
The Catholic university of Korea Daegu hospital
City
Daegu
Country
Korea, Republic of
Facility Name
DongGuk university Gyeongju hospital
City
Gyeongju
Country
Korea, Republic of
Facility Name
DongGuk university Ilsan hospital
City
Ilsan
Country
Korea, Republic of
Facility Name
Inje university Ilsan Paik hospital
City
Ilsan
Country
Korea, Republic of
Facility Name
Gachon university Gil medical center
City
Incheon
Country
Korea, Republic of
Facility Name
Inha university hospital
City
Incheon
Country
Korea, Republic of
Facility Name
Jeju national university hospital
City
Jeju
Country
Korea, Republic of
Facility Name
JeonNam university hospital
City
JeonNam
Country
Korea, Republic of
Facility Name
Kyungbook National university hospital
City
Kyungbook
Country
Korea, Republic of
Facility Name
Gangnam Severance hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Jeil hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Korea university Anam hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Korea university Guro hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Kyunghee university hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Samsung Seoul hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Seoul national university hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Severance hospital
City
Seoul
Country
Korea, Republic of
Facility Name
The Catholic university St. Mary hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Aju university hospital
City
Suwon
Country
Korea, Republic of
Facility Name
YoungNam university hospital
City
YoungNam
Country
Korea, Republic of
12. IPD Sharing Statement
Citations:
PubMed Identifier
28057081
Citation
Rhee MY, Ahn T, Chang K, Chae SC, Yang TH, Shim WJ, Kang TS, Ryu JK, Nah DY, Park TH, Chae IH, Park SW, Lee HY, Tahk SJ, Yoon YW, Shim CY, Shin DG, Seo HS, Lee SY, Kim DI, Kwan J, Joo SJ, Jeong MH, Jeong JO, Sung KC, Kim SY, Kim SH, Chun KJ, Oh DJ. The efficacy and safety of co-administration of fimasartan and rosuvastatin to patients with hypertension and dyslipidemia. BMC Pharmacol Toxicol. 2017 Jan 5;18(1):2. doi: 10.1186/s40360-016-0112-7.
Results Reference
derived
Learn more about this trial
A Randomized, Double-blind, Multicenter, Phase III Study to Evaluate the Efficacy and Safety of Combination of Fimasartan/Rosuvastatin in Comparison to Each Component Administered Alone in Patients With Essential Hypertension and Dyslipidemia
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