Hypertriglyceridemia MedDRA version: 9.1 Level: HLT Classification code 10014486 Term: Elevated triglycerides MedDRA version: 9.1 Level: LLT Classification code 10020870 Term: Hypertriglyceridemia
Conditions
Interventions
Product Name: Ethyl-Eicosapentaenoate [Ethyl-EPA])
Product Code: AMR101
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: ETHYL EICOSAPENTAENOATE
CAS Number: 73310108
Current Sponsor code: Ethyl
Sponsors
Amarin Pharma Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Men or women >18 years of age; • Women may be enrolled if all 3 of the following criteria are met: ? They are not pregnant, ? They are not breastfeeding, and ? They do not plan on becoming pregnant during the study; • Women of childbearing potential must have a negative serum pregnancy test at screening (Visit 1 [Week -8 or Week -6]). Note: Women are not considered to be of childbearing potential if they meet 1 of the following criteria as documented by the investigator: ? They have had a hysterectomy or tubal ligation prior to signing the informed consent form or ? They are post-menopausal, defined as >=1 year since their last menstrual period or have a follicle-stimulating hormone (FSH) level in a menopausal range; • Women of childbearing potential must agree to use an effective method of avoiding pregnancy from screening to the end of the study. Effective methods of avoiding pregnancy are contraceptive methods used consistently and correctly (including implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal contraceptives, intrauterine devices, diaphragm with spermicide, male or female condoms with spermicide, or cervical cap), abstinence, or a sterile sexual partner; • Not on lipid-altering therapy at screening or on 1 of the following lipid altering treatment regimens at screening; • On statin therapy (with or without ezetimibe). Patients currently on statin therapy (with or without ezetimibe) will be evaluated by the investigator as to whether this therapy can be safely discontinued at screening, or if it should be continued. For the criteria of safe withdrawal of statin therapy at screening, see Appendix B. If statin therapy (with or without ezetimibe) is to be continued, dose(s) must be stable for >=4 weeks prior to the TG baseline qualifying measurements for randomization (i.e., Visit 2 [Week -2]) or • On non-statin, lipid-altering medications (niacin >200 mg/day, fibrates, fish oil, other products containing omega-3 fatty acids, or other herbal products or dietary supplements with potential lipid altering effects), either alone or in combination with statin therapy (with or without ezetimibe). Patients currently taking these non-statin, lipid-altering medications must be able to safely discontinue all non-statin, lipid altering therapy at screening. For the criteria of safe withdrawal of non-statin, lipid-altering medications at screening, see Appendix B; • Triglyceride levels >=500 mg/dL and =5.6 mmol/L and =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Body mass index >45 kg/m2; 2. Participation in another clinical trial involving an investigational agent within 30 days prior to screening (Visit 1 [Week -8 or Week -6]); 3. Weight change >3 kg between screening (Visit 1 [Week -8 or Week -6]) and Visit 2 (Week -2); 4. HbA1c >9.5% at screening (Visit 1 [Week -8 or Week -6]); 5. History of stroke, myocardial infarction, life-threatening arrhythmia, or coronary revascularization within 6 months prior to screening; 6. History of acute or chronic pancreatitis; 7. History of symptomatic gallstone disease unless treated with cholecystectomy; 8. Known nephrotic range (>3 g/day) proteinuria; 9. History or evidence of major and clinically significant, hepatic, pulmonary, renal, hematologic, gastrointestinal (including clinically significant malabsorption), endocrine (other than type 1 or type 2 diabetes), immunologic, dermatologic, neurologic, psychiatric, oncologic, or allergic (including drug allergies, but excluding untreated or treated seasonal allergies at the time of dosing) disease that would interfere with the conduct of the study or interpretation of the data; 10. Known lipoprotein lipase impairment or deficiency (Fredrickson Type I), apolipoprotein C-II deficiency, or familial dysbetalipoproteinemia (Fredrickson Type III); 11. Requirement for peritoneal dialysis or hemodialysis for renal insufficiency; 12. History of malignancy, except patients who have been disease-free for >5 years, or whose only malignancy has been basal or squamous cell skin carcinoma; 13. History of bariatric surgery; 14. Uncontrolled hypertension: sitting systolic blood pressure >160 mmHg and/or sitting diastolic blood pressure >100 mmHg; 15. Known to be infected with human immunodeficiency virus (HIV); 16. Positive test for hepatitis B surface antigen or hepatitis C antibody at screening (Visit 1 [Week -8 or Week -6]); 17. Anticipation of major surgery during the screening or double-blind periods of the study; 18. Treatment with chronic prescription pharmacotherapy for metabolic or cardiovascular disease management or risk factor modification (e.g., antihypertensive and antidiabetic medications) that has not been stable for >=4 weeks prior to screening; 19. Ongoing treatment with weight loss drugs (including over the counter); 20. Ongoing treatment with HIV-protease inhibitors, cyclophosphamide, or isotretinoin; 21. Treatment with tamoxifen, estrogens, or progestins that has not been stable for >=4 weeks prior to screening; 22. Routine or anticipated use of all systemic corticosteroids. Use of local or topical corticosteroids is permitted; 23. Thyroid-stimulating hormone (TSH) >1.5 x upper limit of normal (ULN), clinical evidence of hypothyroidism, or thyroid hormone therapy that has not been stable for >=6 weeks prior to screening; 24. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 x ULN; 25. Unexplained creatine kinase concentration >3 × ULN or creatine kinase elevation due to known muscle disease (e.g., polymyositis, mitochondrial dysfunction); 26. Blood donation of >=1 pint (0.5 L) within 30 days prior to screening, or plasma donation within 7 days prior to screening (Visit 1 [Week -8 or Week -6]); 27. Consumption of >2 alcoholic beverages per day following screening; 28. History of illicit drug use within 1 year of screening; 29. Any condition or therapy, which, in the opinion of the investigator, might pose a risk to the patient or make participation in the study not in the patien
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to determine the efficacy of AMR101 2 g daily and 4 g daily, compared to placebo, in lowering fasting TG levels in patients with fasting TG levels >=500 mg/dL and =5.6 mmol/L and <=22.6 mmol/L).;Secondary Objective: 1. To determine the safety and tolerability of AMR101 2 g daily and 4 g daily; 2. To determine the effect of AMR101 on lipid and apolipoprotein profiles; 3. To determine the effect of AMR101 on low-density lipoprotein (LDL) particle number and size; 4. To determine the effect of AMR101 on oxidized LDL; 5. To determine the effect of AMR101 on fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c); 6. To determine the effect of AMR101 on insulin resistance; 7. To determine the effect of AMR101 on high-sensitivity C-reactive protein (hsCRP); 8. To determine the effects of AMR101 2 g daily and 4 g daily on the incorporation of fatty acids into red blood cell membranes and into plasma phospholipids; 9. To explore the relationship between baseline fasting TG levels and the reduction in fasting TG levels; and 10. To explore the relationship between an increase in red blood cell membrane eicosapentaenoic acid (EPA) concentrations and the reduction in fasting TG levels. ;Primary end point(s): The primary efficacy variable for the double-blind treatment period is percent change in TG from baseline to Week 12 endpoint | — |
Countries
Denmark, Finland, Germany, Italy, Netherlands
Outcome results
None listed