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

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.

Study Overview

• Status: Completed
• Conditions: Essential Hypertension, Dyslipidemia
• Intervention / Treatment: Drug: Rosuvastatin; Drug: Fimasartan; Drug: Fimasartan and Rosuvastatin

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Bundang, Korea, Republic of
    • Seoul university Bundang hospital
  • Busan, Korea, Republic of
    • Inje University Busan Paik Hospital
  • Busan, Korea, Republic of
    • Dong-A University Hospital
  • Busan, Korea, Republic of
    • Inje Heaundai Paik hospital
  • ChungNam, Korea, Republic of
    • Chungnam University Hospital
  • Chungnam, Korea, Republic of
    • DanGuk university hospital
  • Daegu, Korea, Republic of
    • The Catholic university of Korea Daegu hospital
  • Gyeongju, Korea, Republic of
    • Dongguk University Gyeongju Hospital
  • Ilsan, Korea, Republic of
    • Inje University Ilsan Paik Hospital
  • Ilsan, Korea, Republic of
    • Dongguk University Ilsan Hospital
  • Incheon, Korea, Republic of
    • Inha University Hospital
  • Incheon, Korea, Republic of
    • Gachon University Gil Medical Center
  • Jeju, Korea, Republic of
    • Jeju National University Hospital
  • JeonNam, Korea, Republic of
    • JeonNam university hospital
  • Kyungbook, Korea, Republic of
    • Kyungbook National university hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Gangnam Severance Hospital
  • Seoul, Korea, Republic of
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of
    • Severance Hospital
  • Seoul, Korea, Republic of
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of
    • Samsung Seoul Hospital
  • Seoul, Korea, Republic of
    • KyungHee University Hospital
  • Seoul, Korea, Republic of
    • Jeil hospital
  • Seoul, Korea, Republic of
    • The Catholic university St. Mary hospital
  • Suwon, Korea, Republic of
    • Aju University Hospital
  • YoungNam, Korea, Republic of
    • Youngnam University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients who voluntarily signed informed consent for participating in this clinical trial
2. Male and female between 20 and 75 years old
3. Patients must have been confirmed essential hypertension and dyslipidemia at Screening visit (Visit1)

4. 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%
5. Subject must be able to understand the trial procedures and be willing to cooperate and complete the trial.

Exclusion Criteria:

1. 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.
2. Patients with the mean SiSBP from 3 times of measurement of over 20mmHg.
3. 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)
4. Secondary dyslipidemia: nephrotic syndrome, dysproteinemia, obstructive hepatopathy or Cushing's syndrome.
5. Patients with fasting TG ≥ 400mg/dL at Pre-Baseline visit (Visit2) assessment
6. History of myopathy, rhabdomyolysis or/and CK ≥ 2 times upper normal limit.
7. 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)
8. 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.
9. Clinically significant hypokalemia(less than 3.5 mmol/L) or hyperkalemia (exceeded 5.5 mmol/L) measured at Pre-Baseline visit (Visit2)
10. 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.
11. Subjects with depletion of body fluid or sodium ion not able to correct
12. 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)
13. 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.
14. Subjects with clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter or any other clinical significant arrhythmia conditions at discretion of investigator
15. Subjects with hypertrophic obstructive cardiomyopathy, severe obstructive coronary artery disease, aortic stenosis, hemodynamically significant aortic valve stenosis, or mitral valve stenosis.
16. Subjects with severe cerebrovascular disorder (e.g. stroke, cerebral infarction or cerebral hemorrhage within the past 6 months)
17. 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.
18. Subjects with known moderate or malignant retinosis (e.g. retinal hemorrhage, visual disturbance or retinal microaneurysm in the past 6 months)
19. Subjects with hepatitis B (including positive test for HBsAg), hepatitis C-positive
20. Subjects with history or evidence of abusing drugs or alcohol within the past 2 years.
21. 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.
22. Medical history with clinically significant hypersensitivity to any components or other drugs on the investigational product or additives (yellow 5)
23. Subjects with hereditary disorders of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
24. Pregnant women and lactating female.
25. 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)
26. Subjects who are participating in another trial or took other investigational product within 12 weeks prior to Screening visit
27. Medical history of all kinds of malignant tumor including leukemia and lymphoma in the past 5 years
28. A subject with other reasons not specified above that, ineligible to participate in this clinical trial at discretion of study investigators.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Fimasartan and Rosuvastatin; Combination of Fimasartan and Rosuvastatin	Drug: Fimasartan and Rosuvastatin
ACTIVE_COMPARATOR: Fimasartan; Fimasartan monotherapy	Drug: Fimasartan
ACTIVE_COMPARATOR: Rosuvastatin; Rosuvastatin monotherapy	Drug: Rosuvastatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	8 weeks from Baseline Visit
Change of SiSBP at week 8 of Fimasartan/Rosuvastatin combination administration from the Baseline to compare the one of Rosuvastatin 20mg single administration	8 weeks from Baseline Visit

Collaborators and Investigators

• Sponsor: Boryung Pharmaceutical Co., Ltd
• Investigators: Study Chair: Dongjoo Oh, Korea University Guro Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (ACTUAL): September 1, 2015
• Study Completion (ACTUAL): September 1, 2015

Study Registration Dates

• First Submitted: June 16, 2014
• First Submitted That Met QC Criteria: June 17, 2014
• First Posted (ESTIMATE): June 18, 2014

Study Record Updates

• Last Update Posted (ACTUAL): February 13, 2017
• Last Update Submitted That Met QC Criteria: February 9, 2017
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Lipid Metabolism Disorders; Hypertension; Dyslipidemias; Essential Hypertension; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: BR-FRC-CT-301