Efficacy of Ethyl Icosapentate in Patients With Severe Hypertriglyceridemia

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)