Exploratory Study of the Effect of Omega-3-acid Ethyl Esters (TAK-085) on Vascular Endothelial Function in Patients With Hyperlipidemia by Flow Mediated Dilation

NCT02824432 | Completed Phase 4 Results

• 3 other identifiers: TAK-085-4001U1111-1182-6745JapicCTI-163269
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to explore the effects of omega-3-acid ethyl esters (TAK-085) on vascular endothelial function when administered for 8 weeks, as measured by FMD, in patients with hyperlipidemia.

Conditions

Hyperlipidemia

Outcome Measures

Primary Outcomes (3)

• Flow-mediated Dilation (FMD) With Fasting State at Baseline, Week 4 and Week 8

  FMD refers to dilation (widening) of an artery when blood flow increases in that artery. To determine FMD, brachial artery dilation following a transient period of forearm ischemia is measured using ultrasound. FMD was calculated by the value of Maximum diastolic vessel size minus vessel size at rest, divided by vessel size at rest, described with percentage.

  Prior to meal at Baseline, Week 4, and Week 8

• Change From Baseline in FMD With Fasting State at Week 4 and Week 8

  FMD refers to dilation (widening) of an artery when blood flow increases in that artery. To determine FMD, brachial artery dilation following a transient period of forearm ischemia is measured using ultrasound. FMD was calculated by the value of Maximum diastolic vessel size minus vessel size at rest, divided by vessel size at rest, described with percentage.

  Prior to meal at Baseline and Week 4, and Week 8

• Percent Change From Baseline in FMD With Fasting State at Baseline, Week 4 and Week 8

  FMD refers to dilation (widening) of an artery when blood flow increases in that artery. To determine FMD, brachial artery dilation following a transient period of forearm ischemia is measured using ultrasound. FMD was calculated by the value of Maximum diastolic vessel size minus vessel size at rest, divided by vessel size at rest, described with percentage.

  Prior to meal at Baseline and Week 4, and Week 8

Secondary Outcomes (32)

• FMD With 4-Hours Postprandial State at Baseline and Week 8

  4-hours after meal at Baseline and Week 8

• Change From Baseline in FMD With 4-Hours Postprandial State at Week 8

  4-hours after meal at Baseline and Week 8

• Percent Change From Baseline in FMD With 4-Hours Postprandial State at Week 8

  4-hours after meal at Baseline and Week 8

• Triglyceride (TG) Level With Fasting State at Baseline, Week 4, and Week 8

  Prior to meal at Baseline, Week 4, and Week 8

• Change From Baseline in TG Level With Fasting State at Week 4 and Week 8

  Prior to meal at Baseline and Week 4, and Week 8

Study Arms (2)

TAK-085 2g

EXPERIMENTAL

A dose of 2 grams of omega-3-acid ethyl esters (TAK-085) will be orally administered once a day immediately after meal.

Drug: TAK-085

TAK-085 4g

EXPERIMENTAL

A dose of 4 grams of omega-3-acid ethyl esters (TAK-085) will be orally administered twice a day immediately after meal.

Drug: TAK-085

Interventions

TAK-085 DRUG

TAK-085 capsules

TAK-085 2g; TAK-085 4g

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with the diagnosis of hyperlipidemia and receiving instructions for lifestyle improvement
• Participants with a fasting TG level of 150 -499 mg/dL at Visit 1 after informed consent (Day -29 to Day -1 before start of study drug administration)
• Participants receiving a stable dose of HMG-CoA reductase inhibitor therapy continuously for at least 4 weeks before informed consent at Visit 1 (Day -29 to Day -1 before start of study drug administration)
• Male or postmenopausal female participants
• Participants who, in the opinion of the principal investigator or the investigator, are capable of understanding the content of the clinical research and complying with the research protocol requirements.
• Participants who can provide written informed consent prior to the conduction of the clinical research procedures
• Participants aged ≥20 years at the time of informed consent at Visit 1(Day -28 to Day 0 before the start of study drug administration)

You may not qualify if:

• Participants with a history of revascularization or those have had coronary artery disease (a definitive diagnosis of myocardial infarction, angina) within 24 weeks before informed consent at Visit 1 (Day -29 to Day -1 before the start of study drug administration)
• Participants who have undergo aortic aneurysmectomy within 24 weeks prior to informed consent at Visit 1 (Day -29 to Day -1 before the start of study drug administration) or those with concurrent aortic aneurysm
• Participants who have had clinically significant hemorrhagic disorders (e.g., hemophilia, capillary fragility, gastrointestinal ulcer, urinary tract hemorrhage, hemoptysis, and vitreous hemorrhage) within 24 weeks prior to informed consent at Visit 1 (Day -29 to Day -1 before the start of study drug administration) or those who concurrently have the above disorders
• Participant with a fasting FMD level of 0% measured at the start of study drug administration at Visit 2 (Day -15 to Day -1 before the start of study drug administration)
• Participants in whom the type and dosage of HMG-CoA reductase inhibitors, antidiabetic drugs and antihypertensive drugs have been changed within 4 weeks prior to informed consent at Visit 1 (Day -29 to Day -1 before the start of study drug administration)
• Participants who have started anti dyslipidemic agents within 4 weeks prior to informed consent at Visit 1 (Day -29 to Day -1 before the start of study drug administration)
• Participants requiring a change in the dose of dyslipidemia therapeutic, antidiabetic, or antihypertensive drugs during the period between informed consent at Visit 1 (Day -29 to Day -1 before the start of study drug administration) and the start of study drug administration at Visit 2 (Day -15 to Day -1 before the start of study drug administration)
• Participants with severe hepatic dysfunction
• Participants with severe renal dysfunction (as an indicator, CKD category ≥G3b, equivalent to an A3)
• Participants who have been diagnosed with pancreatitis
• Participants who have been diagnosed with lipoprotein lipase deficiency, apoprotein C-II deficiency, familial hypercholesterolemia, familial combined hyperlipidemia, or familial type III hyperlipidemia
• Participants with concurrent Cushing's syndrome, uremia, systemic lupus erythematosus (SLE), serum dysproteinemia, or hypothyroidism
• Participants with symptomatic Peripheral Arterial Disease (PAD)
• Participants with concurrent hypertension of grade II or higher Note 1) Note 1: Participants with systolic blood pressure of ≥160 mm Hg or diastolic BP of ≥100 mm Hg regardless of treatment with antihypertensive drugs
• Participants who are habitual drinkers drinking an average of over 100 mL per day (expressed in terms of quantity of alcohol) or participants with, or with a history of drug abuse or addiction Note 2)

Sponsors & Collaborators

• Takeda: lead

Study Sites (4)

Unknown Facility

Yufu, Oita Prefecture, Japan

Location

Unknown Facility

Shinjuku, Tokyo, Japan

Location

Unknown Facility

Kagoshima, Japan

Location

Unknown Facility

Ōita, Japan

Location

Related Publications (1)

• Teramoto T, Shibata H, Suzaki Y, Matsui S, Uemura N, Tomiyama H, Yamashina A. Discrepancy Between Fasting Flow-Mediated Dilation and Parameter of Lipids in Blood: A Randomized Exploratory Study of the Effect of Omega-3 Fatty Acid Ethyl Esters on Vascular Endothelial Function in Patients With Hyperlipidemia. Adv Ther. 2020 May;37(5):2169-2183. doi: 10.1007/s12325-020-01286-1. Epub 2020 Mar 21.

  PMID: 32200533 DERIVED

MeSH Terms

Conditions

Hyperlipidemias

Interventions

TAK-085

Condition Hierarchy (Ancestors)

Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2016
• First Posted: July 6, 2016
• Study Start: August 4, 2016
• Primary Completion: August 19, 2017
• Study Completion: August 19, 2017
• Last Updated: May 6, 2019
• Results First Posted: May 6, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will share

Locations

JP (4)