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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 (Oasis Flow)

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ClinicalTrials.gov Identifier: NCT02824432
Recruitment Status : Completed
First Posted : July 6, 2016
Results First Posted : May 6, 2019
Last Update Posted : May 6, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda

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.

Condition or disease Intervention/treatment Phase
Hyperlipidemia Drug: TAK-085 Phase 4

Detailed Description:

This is a multicenter, collaborative, randomized, open-label study designed to explore the effects of administration of omega-3-acid ethyl esters (TAK-085) [2 g (2 g PO QD) or 4 g (2 g PO BID) for 8 weeks] on vascular endothelial function, as measured by flow-mediated dilation (FMD), in patients receiving a hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor and have concurrent hypertriglyceridemia.

Considering the potential bias by factors that affect FMD between treatment groups, stratified allocation will be performed with fasting triglyceride (TG) level as a factor.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Exploratory Study of the Effect of Omega-3-acid Ethyl Esters on Vascular Endothelial Function in Patients With Hyperlipidemia by Flow Mediated Dilation
Actual Study Start Date : August 4, 2016
Actual Primary Completion Date : August 19, 2017
Actual Study Completion Date : August 19, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TAK-085 2g
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 capsules

Experimental: TAK-085 4g
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
TAK-085 capsules




Primary Outcome Measures :
  1. Flow-mediated Dilation (FMD) With Fasting State at Baseline, Week 4 and Week 8 [ Time Frame: Prior to meal 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.

  2. Change From Baseline in FMD With Fasting State at Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline and 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.

  3. Percent Change From Baseline in FMD With Fasting State at Baseline, Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline and 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.


Secondary Outcome Measures :
  1. FMD With 4-Hours Postprandial State at Baseline and Week 8 [ Time Frame: 4-hours after meal at Baseline 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.

  2. Change From Baseline in FMD With 4-Hours Postprandial State at Week 8 [ Time Frame: 4-hours after meal at Baseline 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.

  3. Percent Change From Baseline in FMD With 4-Hours Postprandial State at Week 8 [ Time Frame: 4-hours after meal at Baseline 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.

  4. Triglyceride (TG) Level With Fasting State at Baseline, Week 4, and Week 8 [ Time Frame: Prior to meal at Baseline, Week 4, and Week 8 ]
  5. Change From Baseline in TG Level With Fasting State at Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline and Week 4, and Week 8 ]
  6. Percent Change From Baseline in TG Level With Fasting State at Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline and Week 4, and Week 8 ]
  7. TG Level With 4-Hours Postprandial State at Baseline, Week 4 and Week 8 [ Time Frame: 4-hours after meal at Baseline, Week 4, and Week 8 ]
  8. Change From Baseline in TG Level With 4-Hours Postprandial State at Week 4 and Week 8 [ Time Frame: 4-hours after meal at Baseline and Week 4, and Week 8 ]
  9. Percent Change From Baseline in TG Level With 4-Hours Postprandial State at Week 4 and Week 8 [ Time Frame: 4-hours after meal at Baseline and Week 4, and Week 8 ]
  10. Dihomo-gamma-linolenic Acid Concentration With Fasting State at Baseline, Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline, Week 4 and Week 8 ]
    Samples for plasma fatty acid fractions (Dihomo-gamma-linolenic acid, Arachidonic acid, Eicosapentaenoic acid, Docosahexaenoic acid, EPA/AAratio, and DHA/AAratio) were taken under the fasting condition. Reported data was the observation value at each point.

  11. Change From Baseline in Dihomo-gamma-linolenic Acid Concentration With Fasting State at Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline and Week 4, and Week 8 ]
    Samples for plasma fatty acid fractions (Dihomo-gamma-linolenic acid, Arachidonic acid, Eicosapentaenoic acid, Docosahexaenoic acid, EPA/AAratio, and DHA/AAratio) were taken under the fasting condition. Reported data was the change from baseline in Dihomo-gamma-linolenic acid at each time point.

  12. Percent Change From Baseline in Dihomo-gamma-linolenic Acid Concentration With Fasting State at Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline and Week 4, and Week 8 ]
    Samples for plasma fatty acid fractions (Dihomo-gamma-linolenic acid, Arachidonic acid, Eicosapentaenoic acid, Docosahexaenoic acid, EPA/AAratio, and DHA/AAratio) were taken under the fasting condition. Reported data was the percent change from baseline in Dihomo-gamma-linolenic acid at each time point.

  13. Arachidonic Acid Concentration With Fasting State at Baseline, Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline, Week 4 and Week 8 ]
    Samples for plasma fatty acid fractions (Dihomo-gamma-linolenic acid, Arachidonic acid, Eicosapentaenoic acid, Docosahexaenoic acid, EPA/AAratio, and DHA/AAratio) were taken under the fasting condition. Reported data was the observation value at each point.

  14. Change From Baseline in Arachidonic Acid Concentration With Fasting State at Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline and Week 4, and Week 8 ]
    Samples for plasma fatty acid fractions (Dihomo-gamma-linolenic acid, Arachidonic acid, Eicosapentaenoic acid, Docosahexaenoic acid, EPA/AAratio, and DHA/AAratio) were taken under the fasting condition. Reported data was the change from baseline in Arachidonic acid at each time point.

  15. Percent Change From Baseline in Arachidonic Acid Concentration With Fasting State at Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline and Week 4, and Week 8 ]
    Samples for plasma fatty acid fractions (Dihomo-gamma-linolenic acid, Arachidonic acid, Eicosapentaenoic acid, Docosahexaenoic acid, EPA/AAratio, and DHA/AAratio) were taken under the fasting condition. Reported data was the percent change from baseline in Arachidonic acid at each time point.

  16. Eicosapentaenoic Acid Concentration With Fasting State at Baseline, Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline, Week 4 and Week 8 ]
    Samples for plasma fatty acid fractions (Dihomo-gamma-linolenic acid, Arachidonic acid, Eicosapentaenoic acid, Docosahexaenoic acid, EPA/AAratio, and DHA/AAratio) were taken under the fasting condition. Reported data was the observation value at each point.

  17. Change From Baseline in Eicosapentaenoic Acid Concentration With Fasting State at Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline and Week 4, and Week 8 ]
    Samples for plasma fatty acid fractions (Dihomo-gamma-linolenic acid, Arachidonic acid, Eicosapentaenoic acid, Docosahexaenoic acid, EPA/AAratio, and DHA/AAratio) were taken under the fasting condition. Reported data was the change from baseline in Eicosapentaenoic acid at each time point.

  18. Percent Change From Baseline in Eicosapentaenoic Acid Concentration With Fasting State at Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline and Week 4, and Week 8 ]
    Samples for plasma fatty acid fractions (Dihomo-gamma-linolenic acid, Arachidonic acid, Eicosapentaenoic acid, Docosahexaenoic acid, EPA/AAratio, and DHA/AAratio) were taken under the fasting condition. Reported data was the percent change from baseline in Eicosapentaenoic acid at each time point.

  19. Docosahexaenoic Acid Concentration With Fasting State at Baseline, Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline, Week 4 and Week 8 ]
    Samples for plasma fatty acid fractions (Dihomo-gamma-linolenic acid, Arachidonic acid, Eicosapentaenoic acid, Docosahexaenoic acid, EPA/AAratio, and DHA/AAratio) were taken under the fasting condition. Reported data was the observation value at each point.

  20. Change From Baseline in Docosahexaenoic Acid Concentration With Fasting State at Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline and Week 4, and Week 8 ]
    Samples for plasma fatty acid fractions (Dihomo-gamma-linolenic acid, Arachidonic acid, Eicosapentaenoic acid, Docosahexaenoic acid, EPA/AAratio, and DHA/AAratio) were taken under the fasting condition. Reported data was the change from baseline in Docosahexaenoic acid at each time point.

  21. Percent Change From Baseline in Docosahexaenoic Acid Concentration With Fasting State at Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline and Week 4, and Week 8 ]
    Samples for plasma fatty acid fractions (Dihomo-gamma-linolenic acid, Arachidonic acid, Eicosapentaenoic acid, Docosahexaenoic acid, EPA/AAratio, and DHA/AAratio) were taken under the fasting condition. Reported data was the percent change from baseline in Docosahexaenoic acid at each time point.

  22. Eicosapentaenoic Acid to Arachidonic Acid (EPA/AA) Ratio With Fasting State at Baseline, Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline, Week 4 and Week 8 ]
    Samples for plasma fatty acid fractions (Dihomo-gamma-linolenic acid, Arachidonic acid, Eicosapentaenoic acid, Docosahexaenoic acid, EPA/AAratio, and DHA/AAratio) were taken under the fasting condition.

  23. Change From Baseline in EPA/AA Ratio With Fasting State at Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline and Week 4, and Week 8 ]
    Samples for plasma fatty acid fractions (Dihomo-gamma-linolenic acid, Arachidonic acid, Eicosapentaenoic acid, Docosahexaenoic acid, EPA/AAratio, and DHA/AAratio) were taken under the fasting condition. Reported data was the change from baseline in EPA/AA Ratio at each time point.

  24. Percent Change From Baseline in EPA/AA Ratio With Fasting State at Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline and Week 4, and Week 8 ]
    Samples for plasma fatty acid fractions (Dihomo-gamma-linolenic acid, Arachidonic acid, Eicosapentaenoic acid, Docosahexaenoic acid, EPA/AAratio, and DHA/AAratio) were taken under the fasting condition. Reported data was the percent change from baseline in EPA/AA Ratio at each time point.

  25. Docosahexaenoic Acid to Arachidonic Acid (DHA/AA) Ratio With Fasting State at Baseline, Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline, Week 4 and Week 8 ]
    Samples for plasma fatty acid fractions (Dihomo-gamma-linolenic acid, Arachidonic acid, Eicosapentaenoic acid, Docosahexaenoic acid, EPA/AAratio, and DHA/AAratio) were taken under the fasting condition.

  26. Change From Baseline in DHA/AA Ratio With Fasting State at Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline and Week 4, and Week 8 ]
    Samples for plasma fatty acid fractions (Dihomo-gamma-linolenic acid, Arachidonic acid, Eicosapentaenoic acid, Docosahexaenoic acid, EPA/AAratio, and DHA/AAratio) were taken under the fasting condition. Reported data was the change from baseline in DHA/AA ratio at each time point.

  27. Percent Change From Baseline in DHA/AA Ratio With Fasting State at Week 4 and Week 8 [ Time Frame: Prior to meal at Baseline and Week 4, and Week 8 ]
    Samples for plasma fatty acid fractions (Dihomo-gamma-linolenic acid, Arachidonic acid, Eicosapentaenoic acid, Docosahexaenoic acid, EPA/AAratio, and DHA/AAratio) were taken under the fasting condition. Reported data was the percent change from baseline in DHA/AA ratio at each time point.

  28. Number of Participants Reporting One or More Adverse Events (AEs) [ Time Frame: Up to Week 8 ]
  29. Number of Participants Reporting One or More AEs Related to Body Weight [ Time Frame: Up to Week 8 ]
  30. Number of Participants Reporting One or More AEs Related to Blood Pressure in the Sitting Position [ Time Frame: Up to Week 8 ]
  31. Number of Participants Reporting One or More AEs Related to Pulse in the Sitting Position [ Time Frame: Up to Week 8 ]
  32. Number of Participants Reporting One or More AEs Related to Laboratory Tests of Fasting Plasma Glucose [ Time Frame: Up to Week 8 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Participants with the diagnosis of hyperlipidemia and receiving instructions for lifestyle improvement
  2. 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)
  3. 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)
  4. Male or postmenopausal female participants
  5. 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.
  6. Participants who can provide written informed consent prior to the conduction of the clinical research procedures
  7. 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)

Exclusion Criteria:

  1. 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)
  2. 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
  3. 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
  4. 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)
  5. 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)
  6. 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)
  7. 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)
  8. Participants with severe hepatic dysfunction
  9. Participants with severe renal dysfunction (as an indicator, CKD category ≥G3b, equivalent to an A3)
  10. Participants who have been diagnosed with pancreatitis
  11. Participants who have been diagnosed with lipoprotein lipase deficiency, apoprotein C-II deficiency, familial hypercholesterolemia, familial combined hyperlipidemia, or familial type III hyperlipidemia
  12. Participants with concurrent Cushing's syndrome, uremia, systemic lupus erythematosus (SLE), serum dysproteinemia, or hypothyroidism
  13. Participants with symptomatic Peripheral Arterial Disease (PAD)
  14. 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
  15. 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)
  16. Participants with a history of hypersensitivity or allergy for omega-3-acid ethyl esters-
  17. Participants who smoke
  18. Participants participating in other clinical studies
  19. Participants who have been determined to be ineligible as subjects in the study by the principal investigator or the investigator

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02824432


Locations
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Japan
Yufu, Oita, Japan
Shinjuku, Tokyo, Japan
Kagoshima, Japan
Oita, Japan
Sponsors and Collaborators
Takeda
Investigators
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Study Director: Study Director Takeda
  Study Documents (Full-Text)

Documents provided by Takeda:
Study Protocol  [PDF] July 7, 2016
Statistical Analysis Plan  [PDF] November 14, 2017

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02824432    
Other Study ID Numbers: TAK-085-4001
U1111-1182-6745 ( Other Identifier: WHO )
JapicCTI-163269 ( Registry Identifier: JapicCTI )
First Posted: July 6, 2016    Key Record Dates
Results First Posted: May 6, 2019
Last Update Posted: May 6, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hyperlipidemias
Hyperlipoproteinemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases