Efficacy of Ethyl Icosapentate in Patients With Severe Hypertriglyceridemia

Mochida Pharmaceutical

Status and phase: Completed; Phase 3

Conditions: Hypertriglyceridemia

Treatments: Drug: Placebo; Drug: Ethyl Icosapentate

Study type: Interventional

Funder types: Industry

Identifiers

NCT04239950

MND2112H33

20191474 (Registry Identifier)

Details and patient eligibility

About

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

Enrollment: 316 patients

Sex: All

Ages: 18 to 74 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. 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
2. Patients who receive instructions for lifestyle improvement and are able to comply with all instructions throughout the study participation period
3. Patients who are 18 to < 75 years of age, regardless of sex, at the time of informed consent
4. Patients who have provided written consent to participate in this clinical trial
5. Patients whose serum TG level (fasting) is less than 2,000 mg/dL at Week -2
6. Patients whose serum TG level (fasting) is less than 2,000 mg/dL at Week -1
7. 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
8. Outpatients

Exclusion Criteria:

1. Patients whose HbA1c from week -6 to week -4 is 8.0% or higher

2. 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

3. Patients with, or with a history of, angina pectoris or myocardial infarction

4. Patients with a history of percutaneous transluminal coronary angioplasty or coronary artery bypass grafting

5. Patients with familial lipoprotein lipase (LPL) deficiency, familial apolipoprotein C-II (apo C-II) deficiency, or familial type III, IV hyperlipidemia

6. Patients with hypothyroidism, Cushing's syndrome, acromegaly, nephrotic syndrome, chronic renal failure, systemic lupus erythematosus, myeloma, or nonalcoholic steatohepatitis (NASH)

7. Patients with hyperlipidemia induced by drugs (e.g., corticosteroids, beta-blockers, contraceptives, interferons, retinoids, and diuretics)

8. Patients with, or with a history of, alcohol dependence or abuse or patients whose hyperlipidemia is presumed to be primarily caused by alcohol

9. Patients with aortic aneurysm or who have undergone aortic aneurysmectomy within the last 6 months

10. 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))

11. Patients with, or with a history of, pancreatitis or patients suspected as pancreatitis by examination, etc

12. Patients with a diagnosis of complication of pancreas or bile duct-related neoplastic disease

13. Patients with type 1 diabetes mellitus or type 2 diabetes mellitus requiring insulin therapy

14. 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

15. Patients who have taken any EPA product

16. Patients who have received a PCSK9 (human proprotein convertase subtilisin/kexin type 9) inhibitor to treat hyperlipidemia

17. Patients who have taken antihyperlipidemic drugs within the last 4 weeks

18. Pregnant, possibly pregnant, or lactating women

19. Patients with a history of hypersensitivity to polyunsaturated fatty acids or gelatin

20. Patients with, or with a history of, malignant tumor

21. Patients with any serious disease, including hepatic, renal, hematologic, respiratory, GI, cardiovascular, psychological, neurologic, metabolic, and electrolyte disorders, or hypersensitivity

22. Patients who have received any other investigational drug within the last 3 months

23. Patients who are judged by the principal (or sub-) investigator to be ineligible as a study subject for any other reason

24. Patients with a systolic blood pressure of ≥180 mmHg or a diastolic blood pressure of ≥110 mmHg at Visit 2 (Week -2))

25. 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)

26. Patients with a systolic blood pressure of ≥180 mmHg or a diastolic blood pressure of ≥110 mmHg at Visit 3 (Week -1)

27. Patients with an HbA1c level of ≥8.0% at Visit 2 (Week -2)

28. Patients whose ALT or AST is more than 3 times the upper limit of normal at Visit 2 (Week -2)

29. Patients with a systolic blood pressure of ≥180 mmHg or a diastolic blood pressure of ≥110 mmHg at Visit 4 (Week 0)

30. Patients with an HbA1c level of ≥8.0% at Visit 3 (Week -1)

31. Patients whose ALT or AST is more than 3 times the upper limit of normal at Visit 3 (Week -1)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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316 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo, orally, twice daily after breakfast and dinner for 12 weeks.

Treatment:

Drug: Placebo

Ethyl Icosapentate 1.8g

Experimental group

Description:

Ethyl Icosapentate 0.9g, orally, twice daily after breakfast and dinner for 12 weeks.

Treatment:

Drug: Ethyl Icosapentate

Ethyl Icosapentate 3.6g

Experimental group

Description:

Ethyl Icosapentate 1.8g, orally, twice daily after breakfast and dinner for 12 weeks.

Treatment:

Drug: Ethyl Icosapentate