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

Phase 3

Completed

• Conditions: Hypertriglyceridemia
• Interventions: Drug: omega-3-acid ethyl esters 90 (TAK-085); Drug: Eicosapentaenoic acid-ethyl (EPA)

• Registration Number: NCT01350999
• Lead Sponsor: Takeda

Brief Summary

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

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.

Study Timeline

• Study Start: 2009-11
• Primary Completion: 2011-01
• Study Completion: 2011-01
• Study First Submitted: 2011-05-09
• Study First Submitted QC: 2011-05-09
• Study First Posted: 2011-05-10
• Results First Submitted: 2016-06-01
• Status Verified: 2016-07
• Results First Submitted QC: 2016-07-28
• Last Update Submitted: 2016-07-28
• Results First Posted: 2016-09-20
• Last Update Posted: 2016-09-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 503

Inclusion Criteria

Visit 1 (Week -4)

1. Undergoing lifestyle modification.

2. Triglyceride (TG) level (fasting state) 150 mg/dL or higher and less than 750 mg/dL at Visit 1 (Week -4).

3. Both genders, aged from 20 to less than 75 years at the time of signing informed consent.

4. Outpatient.

5. Capable of understanding and complying with protocol requirements.

6. Signed a written, informed consent form prior to the initiation of any study procedures.

7. 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)

8. Fasting TG level 150 mg/dL or higher and less than 750 mg/dL at Visit 2 (Week -2).

9. 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

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Exclusion Criteria

Visit 1 (Week -4)

1. 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.

2. Received aortic aneurysmectomy or had had aortic aneurysm within 6 months prior to Visit 1 (Week -4).

3. 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).

4. Diagnosed with pancreatitis.

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

6. Cushing's syndrome, uremia, systemic lupus erythematosus (SLE) or serum dysproteinemia.

7. 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).

8. 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.

9. 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.

10. If female, was pregnant or lactating.

11. 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.

12. Started to take any antihyperlipidemic drugs within 4 weeks prior to Visit 1 (Week -4).

13. Received any investigational products (including those for post-marketing clinical study) within 12 weeks prior to Visit 1 (Week -4).

14. Received TAK-085 in a clinical study.

15. Judged as being ineligible for study participation by the investigator or subinvestigator for any other reasons.

    Visit 2 (Week -2)

16. ALT or AST level at Visit 2 (Week -2) was twice the upper limit of the normal reference range or higher.

17. 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.

18. Judged as being ineligible for study participation by the investigator or subinvestigator for any other reasons.

    Visit 3 (Week 0)

19. 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.

20. Judged as being ineligible for study participation by the investigator or subinvestigator for any other reasons

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TAK-085 2 g	omega-3-acid ethyl esters 90 (TAK-085)	TAK-085 2 g, orally, once daily for up to 52 weeks.
TAK-085 4 g	omega-3-acid ethyl esters 90 (TAK-085)	TAK-085 2 g, orally, twice daily for up to 52 weeks.
EPA-E 1.8 g	Eicosapentaenoic acid-ethyl (EPA)	Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 52 weeks.

Primary Outcome Measures

Name	Time	Method
Number of Participants With TEAEs Associated With Abnormal Changes in Vital Signs	52 Weeks
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	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	52 Weeks	Participants whose results of electrocardiograms were judged as abnormal and clinically significant by investigator after study drug administration were counted in this measure.
Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis	52 Weeks

Secondary Outcome Measures

Name	Time	Method
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 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 Triglyceride Level	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	Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52	Non-high-density lipoprotein cholesterol was calculated by subtracting high-density lipoprotein cholesterol from total cholesterol.