Efficacy of TAK-085 in Participants With Hypertriglyceridemia

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

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.

Study Overview

• Status: Completed
• Conditions: Hypertriglyceridemia
• Intervention / Treatment: Drug: Omega-3-acid ethyl esters 90 (TAK-085); Drug: Eicosapentaenoic acid-ethyl (EPA-E)

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.

• Study Type: Interventional
• Enrollment (Actual): 611
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 74 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. 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:

1. 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.
2. Participants who received aortic aneurysmectomy or is complicated with aortic aneurysm within 6 months prior to Visit 1 (Week -8).
3. 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).
4. Participants who have been diagnosed with pancreatitis.
5. Participants who have been diagnosed with lipoprotein lipase (LPL) deficiency, apolipoprotein C-II deficiency or type III familial hyperlipidemia.
6. Participants with complication of Cushing's syndrome, uremia, systemic lupus erythematosus (SLE) or serum dysproteinemia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TAK-085 2 g; TAK-085 2 g, orally, once daily for up to 12 weeks.	Drug: Omega-3-acid ethyl esters 90 (TAK-085); 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.; Other Names: LOVAZA; Omacor
EXPERIMENTAL: TAK-085 4 g; TAK-085 2 g, orally, twice daily for up to 12 weeks.	Drug: Omega-3-acid ethyl esters 90 (TAK-085); 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.; Other Names: LOVAZA; Omacor
EXPERIMENTAL: EPA-E 1.8 g; Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 12 weeks.	Drug: Eicosapentaenoic acid-ethyl (EPA-E); EPA-E, 0.6 g, orally, three-times daily for up to 12 weeks.; 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

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Associate Professor, Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (ACTUAL): December 1, 2010
• Study Completion (ACTUAL): December 1, 2010

Study Registration Dates

• First Submitted: May 9, 2011
• First Submitted That Met QC Criteria: May 9, 2011
• First Posted (ESTIMATE): May 10, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): September 20, 2016
• Last Update Submitted That Met QC Criteria: July 28, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypertriglyceridemia
• Other Study ID Numbers: TAK-085/CCT-002; JapicCTI-090937 (REGISTRY: JapicCTI); U1111-1120-7801 (REGISTRY: WHO); JapicCTI-R140452 (REGISTRY: JapicCTI)