Long-term Efficacy and Safety Study of TAK-085 in Participants With Hypertriglyceridemia

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and efficacy of TAK-085, once daily (QD) or twice daily (BID), compared to ethyl eicosapentaenoate (EPA-E), three times daily (TID) in participants with hypertriglyceridemia undergoing lifestyle modification.

Detailed Description
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TAK-085 is an oral capsule medicine licensed to Takeda Pharmaceutical Company Ltd. TAK-085 contains omega-3 fatty acid ethyl (mainly, ethyl eicosapentaenoate (EPA-E) and ethyl docosahexaenoic acid (DHA-E)). This is a phase 3, open-label, randomized study to evaluate the efficacy and safety of TAK-085. In addition, EPA-E is also administered for 52 weeks for reference to evaluate the safety of TAK-085 in participants with hypertriglyceridemia who are undergoing lifestyle modification. The study period is a total of 56 weeks, comprised of a 4- week screening period and 52 weeks of treatment.

Official Title
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A Phase 3 Long-term Study of TAK-085 in Subjects With Hypertriglyceridemia

Conditions
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Hypertriglyceridemia

Intervention / Treatment
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* Drug: omega-3-acid ethyl esters 90 (TAK-085)
* Drug: Eicosapentaenoic acid-ethyl (EPA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Visit 1 (Week -4) Undergoing lifestyle modification. Triglyceride (TG) level (fasting state) 150 mg/dL or higher and less than 750 mg/dL at Visit 1 (Week -4). Both genders, aged from 20 to less than 75 years at the time of signing informed consent. Outpatient. Capable of understanding and complying with protocol requirements. Signed a written, informed consent form prior to the initiation of any study procedures. A female with childbearing potential (premenopausal and non-sterilized) must have agreed to use routinely adequate contraception from signing of informed consent throughout the duration of the study. Visit 2 (Week -2) Fasting TG level 150 mg/dL or higher and less than 750 mg/dL at Visit 2 (Week -2). Difference in fasting low density lipoprotein-cholesterol (LDL-C) level between Visit 1 (Week -4) and Visit 2 (Week -2) within 25% of the higher value Exclusion Criteria: Visit 1 (Week -4) Any coronary artery diseases (CAD, e.g., confirmed myocardial infarction and angina pectoris) within 6 months prior to Visit 1 (Week -4) or a history of revascularization. Received aortic aneurysmectomy or had had aortic aneurysm within 6 months prior to Visit 1 (Week -4). History or complication of a clinically significant hemorrhagic disease (e.g., hemophilia, capillary fragility illness, digestive tract ulcer, urinary tract haemorrhage, hemoptysis, vitreous haemorrhage) within 6 months prior to Visit 1 (Week -4). Diagnosed with pancreatitis. Diagnosed with lipoprotein lipase (LPL) deficiency, apolipoprotein C-II deficiency or type III familial hyperlipidemia. Cushing's syndrome, uremia, systemic lupus erythematosus (SLE) or serum dysproteinemia. Type 1 diabetes mellitus or with uncontrolled type 2 diabetes mellitus defined by glycosylated hemoglobin (HbA1C) level of 8.0% or higher at Visit 1 (Week -4). Stage III hypertension defined by systolic blood pressure of 180 mmHg or higher or diastolic blood pressure of 110 mmHg or higher regardless of the use of antihypertensive medication. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level at Visit 1 (Week -4) was not less than twice the upper limit of the normal reference range. If female, was pregnant or lactating. Habitual drinking defined by an average daily alcohol intake of 100 mL or more , drug abuse or drug dependency, or a history of any of these conditions. Started to take any antihyperlipidemic drugs within 4 weeks prior to Visit 1 (Week -4). Received any investigational products (including those for post-marketing clinical study) within 12 weeks prior to Visit 1 (Week -4). Received TAK-085 in a clinical study. Judged as being ineligible for study participation by the investigator or subinvestigator for any other reasons. Visit 2 (Week -2) ALT or AST level at Visit 2 (Week -2) was twice the upper limit of the normal reference range or higher. Needed a change in the dose of antihyperlipidemic drugs or antidiabetic drugs, addition of a new drug or a change in the type of the drugs during the screening period. Judged as being ineligible for study participation by the investigator or subinvestigator for any other reasons. Visit 3 (Week 0) Needed a change in the dose of antihyperlipidemic drugs or antidiabetic drugs, addition of a new drug or a change in the type of the drugs during the screening period. Judged as being ineligible for study participation by the investigator or subinvestigator for any other reasons

Ages Eligible for Study
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Minimum Age: 20 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAK-085 2 g<br>TAK-085 2 g, orally, once daily for up to 52 weeks. | Drug: omega-3-acid ethyl esters 90 (TAK-085)<br>* Omega-3-acid ethyl esters 90 (TAK-085) capsules. Each one gram of fatty acid in TAK-085 contains approximately 465 mg of EPA plus 375 mg of docosahexaenoic acid-ethyl as ethyl esters.<br>* Other names: Omacor;|
| Experimental: TAK-085 4 g<br>TAK-085 2 g, orally, twice daily for up to 52 weeks. | Drug: omega-3-acid ethyl esters 90 (TAK-085)<br>* Omega-3-acid ethyl esters 90 (TAK-085) capsules. Each one gram of fatty acid in TAK-085 contains approximately 465 mg of EPA plus 375 mg of docosahexaenoic acid-ethyl as ethyl esters.<br>* Other names: Omacor;|
| Active Comparator: EPA-E 1.8 g<br>Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 52 weeks. | Drug: Eicosapentaenoic acid-ethyl (EPA)<br>* EPA-E capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) |  | 52 Weeks | 
| Number of Participants With TEAEs Associated With Abnormal Changes in Vital Signs |  | 52 Weeks | 
| Number of Participants With TEAEs Associated With Abnormal Changes in Body Weight |  | 52 Weeks | 
| Number of Participants With Clinically Significant Findings in Electrocardiogram After Study Drug Administration | Participants whose results of electrocardiograms were judged as abnormal and clinically significant by investigator after study drug administration were counted in this measure. | 52 Weeks | 
| Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis |  | 52 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Triglyceride Level |  | Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | 
| Percent Change From Baseline in Low-Density Lipoprotein - Cholesterol (LDL-C) |  | Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | 
| Percent Change From Baseline in Total Cholesterol |  | Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | 
| Percent Change From Baseline in High-Density Lipoprotein - Cholesterol (HDL-C) |  | Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | 
| Percent Change From Baseline in Non-High-Density Lipoprotein - Cholesterol | Non-high-density lipoprotein cholesterol was calculated by subtracting high-density lipoprotein cholesterol from total cholesterol. | Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy