Efficacy and Safety of Ezetimibe/Rosuvastatin and Amlodipine Patients With High Blood Pressure and High Cholesterol

A Multi-center, Randomized, Double-blind, Active-controlled, Phase III Trial to Evaluate the Efficacy and Safety of Ezetimibe/Rosuvastatin and Amlodipine Combination Therapy in Essential Hypertension Patients With Primary Hypercholesterolemia

The goal of this clinical trial is to test whether one pill that combines ezetimibe, rosuvastatin, and amlodipine can safely lower cholesterol and blood pressure in Korean adults with high blood pressure and high cholesterol.

Amlodipine is a calcium channel blocker used for the treatment of hypertension. Rosuvastatin is a statin that inhibits HMG-CoA reductase and is widely used for the treatment of hypercholesterolemia. Ezetimibe is a lipid-lowering agent that inhibits intestinal cholesterol absorption and is commonly used in combination with statins.

This multicenter, randomized, double-blind, active-controlled, phase 3 clinical trial evaluates the efficacy and safety of a fixed-dose combination of ezetimibe, rosuvastatin, and amlodipine in Korean adults with essential hypertension and primary hypercholesterolemia. Following a run-in period that includes therapeutic lifestyle modification, participants are randomized in a 1:1:1 ratio to receive ezetimibe/rosuvastatin/amlodipine 10/20/10 mg or amlodipine 10 mg, or ezetimibe/rosuvastatin 10/20 mg for 8 weeks.

A total of 163 participants were enrolled across 21 study sites. Low-density lipoprotein cholesterol (LDL-C) levels and mean sitting systolic blood pressure (MSSBP) are assessed at Weeks 4 and 8. The primary efficacy endpoints are the percent change in LDL-C from baseline at Week 8 and the change in MSSBP from baseline at Week 8. Secondary endpoints include changes in total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, non-HDL-C, and apolipoprotein B (ApoB).

Screening Inclusion Criteria:

• Age 19 years or older at the time of written informed consent
• Diagnosed with essential hypertension and primary hypercholesterolemia, or currently receiving antihypertensive and/or lipid-lowering medication after such diagnosis
• If receiving antihypertensive and/or lipid-lowering therapy at screening, judged by the investigator to be medically appropriate for discontinuation of prior therapy during the clinical trial period
• Able and willing to voluntarily sign the written informed consent form after receiving an explanation of the purpose, methods, and expected effects of the study

Randomization Inclusion Criteria:

• Mean sitting systolic blood pressure (MSSBP) of at least 140 mmHg and less than 180 mmHg, and mean sitting diastolic blood pressure (MSDBP) less than 110 mmHg
• Completion of at least 4 weeks of therapeutic lifestyle modification before administration of the investigational product
• After at least 4 weeks of therapeutic lifestyle modification, fasting LDL-C meeting one of the following criteria:
• Very high-risk group: LDL-C 70 mg/dL or higher in participants with coronary artery disease, atherosclerotic ischemic stroke or transient ischemic attack, or peripheral arterial disease
• High-risk group: LDL-C 100 mg/dL or higher in participants with carotid artery disease, abdominal aneurysm, or diabetes mellitus
• Moderate-risk group: LDL-C 130 mg/dL or higher in participants with 2 or more major risk factors
• Low-risk group: LDL-C 160 mg/dL or higher in participants with 1 or fewer major risk factors
• Fasting triglycerides less than 400 mg/dL and LDL-C 250 mg/dL or lower

Exclusion Criteria:

• MSSBP ≥ 180 mmHg or MSDBP ≥ 110 mmHg at screening or randomization
• Difference between arms at screening of MSSBP ≥ 20 mmHg and MSDBP ≥ 10 mmHg
• History of secondary hypertension or medical history suggestive of secondary hypertension, including coarctation of the aorta, hyperaldosteronism, renal artery stenosis, Cushing disease, pheochromocytoma, or polycystic kidney disease, etc.
• Symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure of 20 mmHg or more or diastolic blood pressure of 10 mmHg or more on standing compared with sitting or supine blood pressure
• Subjects with secondary dyslipidemia
• Severe cardiac disease, including congestive heart failure (NYHA class III or IV), clinically significant arrhythmia, hypertrophic obstructive cardiomyopathy, severe obstructive coronary artery disease, aortic stenosis, or hemodynamically significant stenosis of the aortic or mitral valve
• Unstable angina, myocardial infarction, transient ischemic attack, cerebrovascular disease, coronary artery bypass grafting, or percutaneous coronary intervention within 6 months prior to screening
• Retinal hemorrhage, including visual impairment, within 6 months prior to screening
• Chronic inflammatory disease requiring treatment (e.g., rheumatoid arthritis), or wasting disease, autoimmune disease, or connective tissue disease
• Endocrine or metabolic disease known to affect serum lipids or lipoproteins, including uncontrolled diabetes mellitus (HbA1c > 9%) or uncontrolled thyroid dysfunction (TSH > 1.5 times the upper limit of normal)
• Severe renal or hepatic impairment, defined as AST or ALT > 3 times the upper limit of normal, or serum creatinine > 1.5 times the upper limit of normal
• History of myopathy or rhabdomyolysis, or creatine kinase (CK) > 2 times the upper limit of normal
• Patients who received, before study participation, treatment with medications that may affect lipid levels, including bile acid sequestrants, anti-obesity medications, fibrates, niacin, or systemic steroid therapy; however, participation is permitted if the relevant washout period has been completed.
• Need for treatment with protocol-prohibited concomitant medications during the study period
• History of hypersensitivity to ezetimibe, rosuvastatin, amlodipine, or related drug classes
• Patients with gastrointestinal disease or a history of surgery that may affect drug absorption, distribution, metabolism, or excretion, including current active gastritis, gastrointestinal or rectal bleeding, a history of major gastrointestinal surgery, a history of active inflammatory bowel disease within 12 months before screening, or hereditary disorders such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
• History of drug or alcohol abuse
• Pregnant or breastfeeding participants, or participants unwilling to use appropriate contraception during the study period
• History of malignancy within 5 years before screening, except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, thyroid cancer, or carcinoma in situ of other sites, provided that the disease was successfully treated and there has been no recurrence for at least 3 years; enrollment may be considered at the investigator's medical discretion.
• Use of another investigational product within 4 weeks prior to screening
• Any other condition or circumstance that, in the investigator's judgment, would make the participant unsuitable for study participation