Efficacy of TAK-085 in Participants With Hypertriglyceridemia

Study Overview
=================
Brief Summary
-----------------
The purpose of this study was to determine the efficacy and safety 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
-----------------
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, double-blind, randomized study to evaluate the efficacy and safety of TAK-085 compared to EPA-E in participants with hypertriglyceridemia who are undergoing lifestyle modification. The study period is a total of 20 weeks, comprised of an 8- week screening period and 12 weeks of treatment.

Official Title
-----------------
A Phase 3, Multicenter, Double-blind, Parallel-group Study to Evaluate the Efficacy and Safety of TAK-085 in Subjects With Hypertriglyceridemia.

Conditions
-----------------
Hypertriglyceridemia

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants with values of fasting triglyceride level at Visit 2 (Week -4) and Visit 3 (Week -2) are 150 mg/dL or higher and less than 750 mg/dL, and the difference between these 2 values is within 30% of the higher one. Participants with differences between 2 values of fasting Low density lipoprotein - cholesterol level measured at Visit 2 (Week -4) and Visit 3 (Week -2) are within 25% of the higher one. Exclusion Criteria: Participants who have coronary artery diseases (eg, confirmed myocardial infarction and angina pectoris) within 6 months prior to Visit 1 (Week -8) or participants with a history of revascularization. Participants who received aortic aneurysmectomy or is complicated with aortic aneurysm within 6 months prior to Visit 1 (Week -8). Participants who have a history or complication of a clinically significant hemorrhagic disease (eg, hemophilia, capillary fragility illness, digestive tract ulcer, urinary tract hemorrhage, hemoptysis, vitreous haemorrhage and so forth) within 6 months prior to Visit 1 (Week -8). Participants who have been diagnosed with pancreatitis. Participants who have been diagnosed with lipoprotein lipase (LPL) deficiency, apolipoprotein C-II deficiency or type III familial hyperlipidemia. Participants with complication of Cushing's syndrome, uremia, systemic lupus erythematosus (SLE) or serum dysproteinemia.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 74 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAK-085 2 g<br>TAK-085 2 g, orally, once daily for up to 12 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 12 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: EPA-E 1.8 g<br>Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 12 weeks. | Drug: Eicosapentaenoic acid-ethyl (EPA-E)<br>* EPA-E, 0.6 g, orally, three-times daily for up to 12 weeks.<br>* Other names: Atheropan®;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Triglyceride Level at the Final Visit | The percentage change between triglycerides collected at the end of study drug administration (the end of treatment period or discontinuation) relative to Baseline. Analysis of Covariance (ANCOVA) model was employed, using the Baseline triglyceride level as covariate and the treatment group as an independent variable. | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Triglyceride Level Over Time | The percentage change between triglycerides collected at each study visit relative to Baseline. | Baseline and Weeks 4, 8, 10 and 12 | 
| Percent Change From Baseline in Low-Density Lipoprotein - Cholesterol (LDL-C) Level Over Time | The percentage change between low-density lipoprotein cholesterol collected at each study visit relative to Baseline. Low-density lipoprotein cholesterol particles measured directly by nuclear magnetic resonance. | Baseline and Weeks 4, 8, 10 and 12 | 
| Percent Change From Baseline in Total Cholesterol Over Time | The percentage change between total cholesterol measured at each study visit relative to Baseline. | Baseline and Weeks 4, 8, 10 and 12 | 
| Percent Change From Baseline in High-Density Lipoprotein - Cholesterol (HDL-C) Level Over Time | The percentage change between high-density lipoprotein cholesterol collected at each study visit relative to Baseline. | Baseline and Weeks 4, 8, 10 and 12 | 
| Percent Change From Baseline in Non-High-Density Lipoprotein - Cholesterol Level Over Time | The percentage change between non-high-density lipoprotein cholesterol collected at each study visit relative to Baseline. Non-high-density lipoprotein cholesterol calculated by subtracting high-density lipoprotein cholesterol from total cholesterol. | Baseline and Weeks 4, 8, 10 and 12 | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) |  | 12 Weeks | 
| Number of Participants With TEAEs Associated With Abnormal Changes in Vital Signs |  | 12 Weeks | 
| Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis |  | 12 Weeks | 
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings After Study Drug Administration |  | 12 Weeks | 

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