Vascepa to Accelerate Lipoprotein Uptake and Elimination

NCT03885661 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 823489AMR-01-01-0024
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a Phase 1 pilot/feasibility mechanistic experiment to help clarify the mechanism of action of an EPA-rich fish oil preparation, icosapent ethyl, on lipid changes in statin-treated patients with residual triglyceridemia.

Conditions

Lipid Disorder; Triglycerides High; Dyslipidemias

Outcome Measures

Primary Outcomes (1)

• Change in VLDL-apoB100 Production Rate

  The production rate of very low-density lipoprotein apolipoprotein B100 as determined by stable-isotope lipid kinetics techniques based on a primed constant infusion of deuterated leucine.

  ≥ 13 weeks of observation on randomized treatment assignment

Study Arms (2)

Icosapent ethyl

EXPERIMENTAL

Icosapent ethyl with a total daily dose of 4 grams, as 2 x 1 gram capsules by mouth twice daily, against a statin background

Drug: Icosapent Ethyl 1000 MG [Vascepa]

Usual Care

NO INTERVENTION

Statin background

Interventions

Icosapent Ethyl 1000 MG [Vascepa] DRUG

Icosapent ethyl is an ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA). The empirical formula of icosapent ethyl is C22H34O2 and the molecular weight is 330.51. The chemical name for icosapent ethyl is ethyl all-cis-5,8,11,14,17-icosapentaenoate.

Also known as: AMR101

Icosapent ethyl

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 1. Triglyceridemia, defined as:
• statin-treated TG \> 200 mg/dL -and/or-
• statin-treated TG \> 150 mg/dL -plus- statin-treated HDL \< 45 \[men\] or \< 55 \[women\] 2. Self-reported Caucasian-majority race, defined as 3 out of 4 grandparents Caucasian 3. Subjects between the ages of 21 and 75 years of age inclusive 4. Ability to understand and agree to informed consent 5. Are reliable and willing to make themselves available for the duration of the study, comply with study procedures, agree not to participate in other clinical experiments, and agree not to donate blood products during the study

You may not qualify if:

• \. Use of medications indicated for the treatment of diabetes within 6 weeks of the first experimental visit (see Prohibited Treatments) 3. History of a myocardial infarction (MI), unstable angina leading to hospitalization, coronary artery bypass graft surgery (CABG), percutaneous coronary intervention (PCI), uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, transient ischemic attack, carotid revascularization, endovascular procedure or surgical intervention within 6 months of baseline.
• \. Known inefficacy to TG-lowering doses of fish oils (e.g. \>= 4 caps daily of prescription fish oil or \>= 6 caps daily of supplemental fish oil).
• \. TG \> 500 mg/dL as the average of valid, statin-treated values 6. BMI \> 40 kg/m2 7. BMI \< 20 kg/m2 8. Evidence of previously undiagnosed diabetes: Average fasting glucose during screening \> 125 mg/dL 9. Known familial lipoprotein lipase impairment or deficiency (Fredrickson Type I), Apo C II deficiency, or familial dysbetalipoproteinemia (Fredrickson Type III).
• \. Severe allergy to fish, unless non-allergic response to fish oil is established (n.b. most fish allergies are to the proteins as opposed to the fats, so with highly-purified oils the risk of a true allergy is remote).
• \. Known intolerance or contraindication to Vascepa, and if the former is unknown, known intolerance or contraindication to fish oil 12. Any surgical or medical condition that may interfere with absorption, distribution, metabolism, or excretion of EPA or DHA.
• \. History of extreme triglyceridemia (TG \> 1000 mg/dL) or pancreatitis from triglyceridemia, regardless of whether it is currently controlled.
• \. Medical condition that would prohibit fasting (e.g. diagnosis of insulinoma or postabsorptive hypoglycemia).
• \. Significant disinclination to dairy products (e.g. lactose intolerance, inviolable dietary restrictions). All participants will receive a test dose of the fat challenge during the screening visit, which consists of heavy cream and lactase enzyme. Many people with lactose intolerance successfully avert symptoms by correcting their lactase deficiency with lactase supplements. We will allow these people to participate because we will allow them to take their preferred brand and dose of lactase supplement beyond the lactase in the fat challenge if needed. However, we still require that they are able to tolerate the test dose given during screening.
• \. History of a non-skin malignancy within the previous 5 years. 17. Uncontrolled thyroid disease. 18. Any major active rheumatologic, pulmonary, or dermatologic disease or inflammatory condition.
• \. Major surgery within the previous 6 weeks. 20. Subjects who have undergone any organ transplant. 21. History of illicit drug use within the past 3 years, or regular alcohol use of greater than 14 drinks per week. For clarity, illicit substances are per Federal law or regulations in effect at the time of first approval of this protocol.
• \. Women who are breast-feeding. 23. Women of childbearing potential must have a negative urine pregnancy test at screening and baseline visits and be willing to have additional urine pregnancy tests during the study.
• \. Sexually active subjects (both women and men) must be willing to use a medically accepted method of contraception from screening visit until month after last dose of study drug 25. Significant or unstable medical or psychological conditions, including known or suspected personality disorders, that could compromise the subject's safety or successful participation in the study in the opinion of the investigator.
• \. Subject-reported history of HIV and/or use of HIV medications 27. History of symptomatic gallstone disease unless definitively treated (e.g. condition successfully treated with cholecystectomy without recurrent or residual biliary disease).
• \. History of bariatric surgery or other major gastrointestinal surgery associated with major disruptions to drug absorption.
• \. Anticipation of major surgery during the screening or treatment periods of the study 30. Participants with the following conditions will opt out of heparin exposure for lipase determinations, but will be allowed to participate in the overall protocol.

Sponsors & Collaborators

• University of Pennsylvania: lead
• Amarin Pharma Inc.: collaborator

Study Sites (1)

Perelman School of Medicine at the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Lipid Metabolism Disorders; Hypertriglyceridemia; Dyslipidemias

Interventions

eicosapentaenoic acid ethyl ester

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperlipidemias

Results Point of Contact

• Title: John Millar, PhD
• Organization: University of Pennsylvania

jsmillar@pennmedicine.upenn.edu

215-898-0638

Study Officials

• John Millar, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Reference therapy is usual care, so the subject and coordinators are unblinded to assignment, but investigators and outcomes assessors are blinded to assignment.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel, randomized, controlled mechanistic pilot/feasibility experiment focused on elucidating detailed mechanism of action for apolipoprotein turnover kinetics changes using intravenous infusions of stable isotopes in a clinical/translational metabolic unit.

Study Record Dates

• First Submitted: March 19, 2019
• First Posted: March 21, 2019
• Study Start: January 11, 2016
• Primary Completion: August 1, 2018
• Study Completion: June 1, 2021
• Last Updated: November 11, 2021
• Results First Posted: November 11, 2021

Record last verified: 2021-10

Locations

US (1)