Lipid DisorderPhase 1VALUENCT03885661
Vascepa to Accelerate Lipoprotein Uptake and Elimination
A Phase 1 study testing Icosapent Ethyl 1000 MG [Vascepa] in people with Lipid Disorder and Triglycerides High, run by University of Pennsylvania at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Lipid Disorder, Triglycerides High, Dyslipidemias
- What is being tested?
- Icosapent Ethyl 1000 MG [Vascepa]
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Jan 2016to Jun 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 1. Diagnosis of idiopathic or otherwise active diabetes: History of resolved gestational or drug-induced diabetes is acceptable, but history Type I or Type II diabetes are exclusionary.
- 2. 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.
- 4. 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).
- 5. 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).
- 10. 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).
- 11. 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.
Show all 46Show fewer
- 13. History of extreme triglyceridemia (TG > 1000 mg/dL) or pancreatitis from triglyceridemia, regardless of whether it is currently controlled.
- 14. Medical condition that would prohibit fasting (e.g. diagnosis of insulinoma or postabsorptive hypoglycemia).
- 15. 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.
- 16. 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.
- 19. 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.
- 22. 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.
- 24. 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.
- 26. 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).
- 28. History of bariatric surgery or other major gastrointestinal surgery associated with major disruptions to drug absorption.
- 29. 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.
- 31. History of intolerance or adverse reaction to therapeutic or sub-therapeutic heparin regimens 32. History of intracerebral hemorrhage 33. History of significant GI bleed, unless definitively treated without recurrence 34. Women with dysfunctional uterine bleeding 35. Individuals with clinically-significant coagulopathy at screening 36. Individuals with clinically-significant thrombocytopenia at screening 37. Hemoglobin < 12 g/dL at screening 38. Mean corpuscular volume (MCV) < 80 fL or > 100 fL at screening 39. Donation of whole blood within 8 weeks prior to the first experimental visit. Participation in the screening phase is permitted.
- 40. History of inherent unremediable risks for anemia, such as hemoglobinopathies, hemolytic disorders, and bleeding disorders, regardless of whether their hemoglobin is currently normal.
- 41. History of a large-volume gastrointestinal (GI) bleeding, such as a bleed that required ER evaluation or admission, required acute endoscopic or surgical management, was managed by blood transfusion, or caused anemia.
- 42. History of NSAID-mediated peptic ulcer disease is excluded, irrespective of current medical treatment. A history of peptic ulcer disease from H. pylori does not exclude participation provided H. pylori was successfully eradicated. Other causes of peptic ulcer disease may be allowable, especially if definitively treated or the risk of recurrence is otherwise low.
- 43. Chronic, untreated conditions that predispose to anemia, such as significant iron or B vitamin malabsorption, persistent menorrhagia, or other chronic or intermittent bleeding.
- 44. Participation in an investigational drug study concurrently; participants who previously completed an investigational drug study cannot participate in the first experimental visit until at least 6 weeks after the final dose given during the previous investigational drug study. For the purposes of this exclusion, an investigational drug is a new chemical entity or a pharmaceutical investigated to support an initial new drug application. Furthermore, herbal or other supplements already deemed "generally regarded as safe" or legally sold in the U.S. would not be considered an investigational drug.
- 45. Use of medications indicated for the treatment of diabetes within 6 weeks of the first experimental visit 46. Daily therapy with non-statin lipid-altering medications within 6 weeks of the first experimental visit is exclusionary, including long-term therapy with the agents listed below. Subjects may wash off these medications so long as the first experimental visit occurs at least 6 weeks after chronic therapy ceases. Following a washout period, fasting lipids will be repeated prior to the first experimental visit to assure that these are not exclusionary as defined above.
- Niacin > 100 mg/ day: (Niacor®, Slo-Niacin®, Niaspan®, Advicor®, Simcor®, Inositol Hexanicotinate, or supplemental niacin).
- Fibrates: gemfibrozil (Lopid®), fenofibrate (Antara®, Lofibra®, Tricor®, Triglide®), fenofibric acid (Trilipix®, Certriad®).
- Enterically active lipid altering drugs: colestipol (Colestid®), cholestyramine (Questran®), colesevelam (Welchol®), ezetimibe (Zetia®, Vytorin®), orlistat (Xenical®, Ali®).
- Prescription fish oil: Vascepa®, Epanova®, Lovaza® (nee Omacor®)
- Supplemental omega-3-enriched oils: flaxseed, fish, or algal oils
- Foods enriched with omega-3 fatty acids
- Consumption of up to 2 servings per week of fish is acceptable 47. Lipid-altering supplements
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- Sterol/stanol products (e.g. CholestOff), policosanols
- Dietary fiber supplements, including >2 teaspoons of Metamucil® or psyllium containing supplements per day
- Garlic supplements or soy isoflavones supplements
- Supplemental vitamin B5 or related compounds unless part of a multi-vitamin
- As above, red yeast statin will be switched to a GMP prescription statin
- Any other medications, herbal products, or dietary supplements with known or potential lipid-altering effects 48. Anticoagulant therapy (except aspirin)
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- Warfarin
- Rivaroxiban
- Apixaba
- Dabigantran 49. Anti-obesity medications or their components
- <!-- -->
- Orlistat (Xenical)
- Lorcaserin (Belviq)
- Phentermine plus extended-release topiramate (Qsymia)
Trial locations and contacts
1 site in 1 country.
United States1 site
Perelman School of Medicine at the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Vascepa to Accelerate Lipoprotein Uptake and Elimination (VALUE): An Open-Label, Mechanistic, Randomized, Controlled, Single-Center Trial of AMR101 in Patients With Dyslipidemia
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.
Read the detailed description
This is a prospective randomized, controlled pilot/feasibility experiment in a small number of statin-treated patients with residual triglyceridemia assigned to chronic daily exposure to icosapent ethyl 4 g daily vs usual care to get preliminary data to ultimately design a definitive hypothesis-testing experiment to clarify the mechanism of action whereby icosapent ethyl alters lipoprotein kinetics. The formal statistical aim is to develop statistical parameters such as central tendency, dispersion, and distributional shape to design a robust hypothesis-testing study. The primary outcome is based around stable-isotope lipoprotein kinetics, specifically apolipoprotein B kinetics.
- Conditions
- Lipid Disorder, Triglycerides High, Dyslipidemias
- Being tested
- Icosapent Ethyl 1000 MG [Vascepa]
- Medical subject headings
- Lipid Metabolism Disorders, Hypertriglyceridemia, Dyslipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Icosapent Ethyl 1000 MG [Vascepa]Drug
Also called AMR101
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Icosapent Ethyl 1000 MG [Vascepa] |
| Usual Care | No intervention | Statin background |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: ≥ 13 weeks of observation on randomized treatment assignment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2019
- Study start11 Jan 2016
- Primary completionAug 2018
- Study completionJun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lipid DisorderStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Amarin Pharma Inc.
- Responsible party
- Sponsor
- Investigators
- John Millar, PhD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03885661
- Sponsor's protocol ID
- 823489
- Other IDs
- AMR-01-01-0024
- Acronym
- VALUE
- Status last verified
- Oct 2021
- First submitted
- 19 Mar 2019
- Last updated
- 11 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vascepa to Accelerate Lipoprotein Uptake and Elimination (VALUE): An Open-Label, Mechanistic, Randomized, Controlled, Single-Center Trial of AMR101 in Patients With Dyslipidemia
- ClinicalTrials.gov ID
- NCT03885661
- Acronym / sponsor ID
- VALUE / 823489
- Conditions
- Lipid Disorder, Triglycerides High, Dyslipidemias
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Amarin Pharma Inc.
- Study start
- 11 Jan 2016 (actual)
- Primary completion
- Aug 2018 (actual)
- Study completion
- Jun 2021 (actual)
- First posted
- 21 Mar 2019 (actual)
- Results
- Posted 11 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a prospective randomized, controlled pilot/feasibility experiment in a small number of statin-treated patients with residual triglyceridemia assigned to chronic daily exposure to icosapent ethyl 4 g daily vs usual care to get preliminary data to ultimately design a definitive hypothesis-testing experiment to clarify the mechanism of action whereby icosapent ethyl alters lipoprotein kinetics. The formal statistical aim is to develop statistical parameters such as central tendency, dispersion, and distributional shape to design a robust hypothesis-testing study. The primary outcome is based around stable-isotope lipoprotein kinetics, specifically apolipoprotein B kinetics.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Icosapent ethyl | Experimental | Drug: Icosapent Ethyl 1000 MG [Vascepa]Icosapent ethyl with a total daily dose of 4 grams, as 2 x 1 gram capsules by mouth twice daily, against a statin background |
| Usual Care | No intervention | –Statin background |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (46 listed)
- 2. 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.
- 4. 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).
- 5. 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).
- 10. 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).
- 11. 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Icosapent Ethyl 1000 MG [Vascepa]Also: AMR101Icosapent 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. | Drug | Icosapent ethyl |
Primary outcome
Change in VLDL-apoB100 Production Rate
Time frame: ≥ 13 weeks of observation on randomized treatment assignment
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Millar, PhD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Icosapent Ethyl 1000 MG [Vascepa] in people with Lipid Disorder and Triglycerides High, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 46 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in VLDL-apoB100 Production Rate (time frame: ≥ 13 weeks of observation on randomized treatment assignment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Nov 2021.