Efficacy of Ethyl Icosapentate in Patients With Severe Hypertriglyceridemia

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of ethyl icosapentate in Chinese patients with severe hypertriglyceridemia.

Official Title
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A Multi-center, Randomized, Double-blind, Parallel-group, Placebo Controlled Study to Evaluate the Efficacy and Safety of Ethyl Icosapentate in Patients With Severe Hypertriglyceridemia

Conditions
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Hypertriglyceridemia

Intervention / Treatment
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* Drug: Placebo
* Drug: Ethyl Icosapentate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients whose serum Triglyceride (TG) level (fasting) from week -6 to week -4 is 500 mg/dL or higher and less than 2,000 mg/dL Patients who receive instructions for lifestyle improvement and are able to comply with all instructions throughout the study participation period Patients who are 18 to < 75 years of age, regardless of sex, at the time of informed consent Patients who have provided written consent to participate in this clinical trial Patients whose serum TG level (fasting) is less than 2,000 mg/dL at Week -2 Patients whose serum TG level (fasting) is less than 2,000 mg/dL at Week -1 Patients in whom the average of Week -2 and Week -1 in serum TG level (fasting) is 500 mg/dL or higher and less than 2,000 mg/dL Outpatients Exclusion Criteria: Patients whose HbA1c from week -6 to week -4 is 8.0% or higher Patients whose Alanine Aminotransferase (ALT) or Aspartate aminotransferase (AST) from week -6 to week -4 is more than 3 times the upper limit of normal Patients with, or with a history of, angina pectoris or myocardial infarction Patients with a history of percutaneous transluminal coronary angioplasty or coronary artery bypass grafting Patients with familial lipoprotein lipase (LPL) deficiency, familial apolipoprotein C-II (apo C-II) deficiency, or familial type III, IV hyperlipidemia Patients with hypothyroidism, Cushing's syndrome, acromegaly, nephrotic syndrome, chronic renal failure, systemic lupus erythematosus, myeloma, or nonalcoholic steatohepatitis (NASH) Patients with hyperlipidemia induced by drugs (e.g., corticosteroids, beta-blockers, contraceptives, interferons, retinoids, and diuretics) Patients with, or with a history of, alcohol dependence or abuse or patients whose hyperlipidemia is presumed to be primarily caused by alcohol Patients with aortic aneurysm or who have undergone aortic aneurysmectomy within the last 6 months Patients with uncontrollable hypertension (patients with a systolic blood pressure of ≥180 mmHg or a diastolic blood pressure of ≥110 mmHg in a sitting position at Visit 1 (Week -4)) Patients with, or with a history of, pancreatitis or patients suspected as pancreatitis by examination, etc Patients with a diagnosis of complication of pancreas or bile duct-related neoplastic disease Patients with type 1 diabetes mellitus or type 2 diabetes mellitus requiring insulin therapy Patients with any of the following hemorrhagic findings within the last 6 months: Patients with, or with a history of, clinically significant hemorrhagic disease (e.g., cerebral hemorrhage, hemophilia, capillary fragility, gastrointestinal [GI] ulcer, urinary tract hemorrhage, hemoptysis, vitreous hemorrhage) Patients with clinically significant bleeding tendency (e.g., menorrhagia, frequent epistaxis) Patients with, or with a history of, severe trauma Patients with a history of surgery requiring blood transfusion Patients who have taken any EPA product Patients who have received a PCSK9 (human proprotein convertase subtilisin/kexin type 9) inhibitor to treat hyperlipidemia Patients who have taken antihyperlipidemic drugs within the last 4 weeks Pregnant, possibly pregnant, or lactating women Patients with a history of hypersensitivity to polyunsaturated fatty acids or gelatin Patients with, or with a history of, malignant tumor Patients with any serious disease, including hepatic, renal, hematologic, respiratory, GI, cardiovascular, psychological, neurologic, metabolic, and electrolyte disorders, or hypersensitivity Patients who have received any other investigational drug within the last 3 months Patients who are judged by the principal (or sub-) investigator to be ineligible as a study subject for any other reason Patients with a systolic blood pressure of ≥180 mmHg or a diastolic blood pressure of ≥110 mmHg at Visit 2 (Week -2)) Patients who have changed the dosage of antidiabetic drug (except insulin) or who have switched from one drug to another since Visit 1 (Week -4) Patients with a systolic blood pressure of ≥180 mmHg or a diastolic blood pressure of ≥110 mmHg at Visit 3 (Week -1) Patients with an HbA1c level of ≥8.0% at Visit 2 (Week -2) Patients whose ALT or AST is more than 3 times the upper limit of normal at Visit 2 (Week -2) Patients with a systolic blood pressure of ≥180 mmHg or a diastolic blood pressure of ≥110 mmHg at Visit 4 (Week 0) Patients with an HbA1c level of ≥8.0% at Visit 3 (Week -1) Patients whose ALT or AST is more than 3 times the upper limit of normal at Visit 3 (Week -1)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo, orally, twice daily after breakfast and dinner for 12 weeks. | Drug: Placebo<br>* Placebo<br>|
| Experimental: Ethyl Icosapentate 1.8g<br>Ethyl Icosapentate 0.9g, orally, twice daily after breakfast and dinner for 12 weeks. | Drug: Ethyl Icosapentate<br>* Ethyl Icosapentate<br>|
| Experimental: Ethyl Icosapentate 3.6g<br>Ethyl Icosapentate 1.8g, orally, twice daily after breakfast and dinner for 12 weeks. | Drug: Ethyl Icosapentate<br>* Ethyl Icosapentate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of change from baseline in serum triglyceride level at 12 weeks after the start of study drug administration |  | Baseline and 12 weeks | 
| Adverse events after the start of study drug administration |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of change from baseline in serum total cholesterol level at 12 weeks after the start of study drug administration |  | Baseline and 12 weeks | 
| Percentage of change from baseline in serum low-density lipoprotein cholesterol (LDL-C) level at 12 weeks after the start of study drug administration |  | Baseline and 12 weeks | 
| Percentage of change from baseline in serum high-density lipoprotein cholesterol (HDL-C) level at 12 weeks after the start of study drug administration |  | Baseline and 12 weeks | 
| Adverse drug reaction after the start of study drug administration |  | 12 weeks |