HypertriglyceridemiaPhase 1NCT01431690
Interaction of Epanova on Warfarin Pharmacokinetic and Anticoagulant Activity and Comparison of the Effects of Epanova and Lovaza on Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) After Low-fat Meals
A Phase 1 study testing warfarin, omefas and omega-3-acid ethyl esters in people with Hypertriglyceridemia, run by AstraZeneca at 1 site in United States.
Trial summary
The primary objective of this study is to determine the effect of Epanova® on the pharmacokinetic and anticoagulant activity of warfarin. The secondary objective of this study is to compare the systemic exposure of EPA and DHA following multiple-dose administration of Epanova®, a free fatty acid mixture, to Lovaza®, a… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypertriglyceridemia
- What is being tested?
- warfarin, omefas and omega-3-acid ethyl esters
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2011to Oct 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subject candidates must fulfill all of the following inclusion criteria to be eligible for participation in the study:
- Healthy adult male and/or females, 18 to 55 years of age (inclusive).
- Body mass index (BMI) ≥ 18 and ≤ 29.9 (kg/m2).
- Medically healthy with clinically insignificant screening results. Hemoglobin must be ≥ the lower limit of normal.
- Non-tobacco/nicotine-containing product users for a minimum of 6 months prior to dosing.
- Voluntarily consent to participate in the study and to follow the restrictions and procedures outlined for the study.
- For the Warfarin and Epanova Arm, females must be of non-childbearing potential defined as have undergone sterilization procedures at least 6 months prior to check-in or have been postmenopausal for at least 24 consecutive months prior to check-in of the study and have a screening follicle stimulating hormone level > 40 mIU/mL.
- For the Lovaza Arm, females may be of non-childbearing potential (as outlined above for Warfarin and Lovaza) or be of childbearing potential and must either be sexually inactive (abstinent) for 14 days prior to screening and remain so through 30 days following the final dosing of the study drug or until completion of the subject's first menstrual cycle following the final dosing of the study drug, whichever period of time is longer or have been using one of the acceptable methods of birth control.
Who cannot join
- Subjects may be excluded from the study if there is evidence of any of the following criteria at screening, check-in, or at any time during the study as appropriate.
- For both arms (Warfarin and Epanova, Lovaza)
- Has a history or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal (GI), endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
- Has a positive urine drug/alcohol testing at screening or check-in.
- Has a positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
- Has consumed fish within 7 days prior to check-in.
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- Has used fish oil, other EPA and/or DHA containing supplements within 2 months of check-in.
- Has a history or presence of alcoholism or drug abuse within the 2 years prior to check-in.
- Has a known sensitivity or allergy to soybeans, fish, and/or shellfish.
- Has had a hypersensitivity or idiosyncratic reaction to compounds related to Epanova® and Lovaza®.
- Has used any prescription medication (with the exception of hormonal contraceptives for females in the Lovaza arm) within 14 days prior to check-in.
- Has used any over-the-counter (OTC) medication, including herbal products (e.g., bromelains, danshen, dong quai [Angelica sinesis], garlic, ginko biloba, ginseng, and St. John's wort), within the 7 days prior to check-in. Up to 2 g per day of acetaminophen is allowed at the discretion of the PI for the Lovaza arm.
- Has used any drugs known to significantly inhibit [strong or moderate] or induce liver enzymes involved in drug metabolism [CYP P450]) within 30 days prior to check-in.
- Has donated blood or has had a significant blood loss within 56 days prior to check-in.
- Has donated plasma within 7 days prior to check-in.
- Has participated in another clinical trial within 30 days prior to check-in.
- Is a female who is pregnant or lactating.
- For Warfarin and Epanova Arm only:
- Has taken large daily doses of Vitamin K (exceeding 25 μg/day) or has eaten large quantities (e.g., averaging > 4 portions daily) of dark green/leafy vegetables (e.g., spinach, kale, collard greens, broccoli, Brussels sprouts) during the 2 months prior to check-in.
- Is employed or involved in any circumstance which would place them at increased risk of hemorrhage (e.g., contact sports, strenuous or unaccustomed weight lifting, running, bicycling).
- Has a personal or familial history of bleeding disorder(s), thromboembolic disease, clinical GI bleeding, or any history of GI surgery except uncomplicated appendectomy or cholecystectomy, or colorectal surgery for polyps, nonmalignant tumors, or diverticula.
- Has active severe gingivitis.
- Has had a hypersensitivity or idiosyncratic reaction to compounds related to warfarin.
- Has a recent physical injury (within the 2 weeks prior to screening).
- Has had a major surgery within the 3 months prior to screening.
- Is allergic to Vitamin K.
- Has used non-steroidal anti-inflammatory (NSAID) drugs within the 2 weeks prior to check-in.
- Has a positive fecal occult blood sample at check-in.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, 2-cohort Study to Evaluate the Effect of Multiple Doses of Epanova® on the Single Dose Pharmacokinetics and Pharmacodynamics of Warfarin and to Compare the Systemic Exposure of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) Following Multiple-dose Administrations of Epanova® Compared to Lovaza® in Healthy Normal Subjects
The primary objective of this study is to determine the effect of Epanova® on the pharmacokinetic and anticoagulant activity of warfarin.
The secondary objective of this study is to compare the systemic exposure of EPA and DHA following multiple-dose administration of Epanova®, a free fatty acid mixture, to Lovaza®, a mixture of fatty acid ethyl esters, under low-fat meal conditions since these products are likely to be administered to patients with cardiovascular disease who are recommended to consume low-fat meals.
- Conditions
- Hypertriglyceridemia
- Being tested
- warfarin, omefas, omega-3-acid ethyl esters
- Keywords
- Eicosapentaenoic Acid, Docosahexaenoic Acid, Warfarin, Hypertriglyceridemia, Omega-3 free fatty acids, Omega-3 ethyl ester acids, Epanova, Lovaza, pharmacokinetics, low-fat meal
- Medical subject headings
- Hypertriglyceridemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
warfarinDrug
Also called coumarin-based anticoagulant
A single 25 mg dose of warfarin
omefasDrug
Also called Epanova
4 x 1 g capsule dose of Epanova®
omega-3-acid ethyl estersDrug
Also called Lovaza
4 x 1 g capsule dose of Lovaza®
| Study group | Role | What they receive |
|---|---|---|
| Warfarin and Epanova | Experimental | Not described Receives: Drug: warfarin; Drug: omefas |
| Lovaza | Active comparator | Not described Receives: Drug: omega-3-acid ethyl esters |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics of R- and S- warfarin
The primary endpoints of this study will be the area under the curve (AUC)0-t, AUC0-inf, and maximum concentration (Cmax) of R- and S warfarin and the maximum International Normalized Ratio (INRmax) over 168 hours postdose and INR AUC0-168 when warfarin is administered with and without Epanova®.
Measured: 168 hours
Pharmacodynamics of R- and S- warfarin
The INRmax over 168 hours postdose and INR AUC0-168 when warfarin is administered with and without Epanova®.
Measured: 168 hours
Secondary outcomes (1)
Total EPA+DHA
The AUC0-tau and Cmax of baseline-adjusted total EPA+DHA following multiple doses (14 days) of Epanova® and Lovaza®.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2011 (estimated)
- Study startAug 2011
- Primary completionOct 2011
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypertriglyceridemiaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael H Davidson, MD, FACC, Study director, Omthera Pharmaceuticals, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01431690
- Sponsor's protocol ID
- OM-EPA-006
- Status last verified
- Apr 2015
- First submitted
- 8 Sep 2011
- Last updated
- 24 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, 2-cohort Study to Evaluate the Effect of Multiple Doses of Epanova® on the Single Dose Pharmacokinetics and Pharmacodynamics of Warfarin and to Compare the Systemic Exposure of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) Following Multiple-dose Administrations of Epanova® Compared to Lovaza® in Healthy Normal Subjects
- ClinicalTrials.gov ID
- NCT01431690
- Acronym / sponsor ID
- OM-EPA-006
- Conditions
- Hypertriglyceridemia
- Keywords
- Eicosapentaenoic Acid, Docosahexaenoic Acid, Warfarin, Hypertriglyceridemia, Omega-3 free fatty acids, Omega-3 ethyl ester acids, Epanova, Lovaza
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Aug 2011
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 9 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to determine the effect of Epanova® on the pharmacokinetic and anticoagulant activity of warfarin.
The secondary objective of this study is to compare the systemic exposure of EPA and DHA following multiple-dose administration of Epanova®, a free fatty acid mixture, to Lovaza®, a mixture of fatty acid ethyl esters, under low-fat meal conditions since these products are likely to be administered to patients with cardiovascular disease who are recommended to consume low-fat meals.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Warfarin and Epanova | Experimental | Drug: warfarin, Drug: omefas |
| Lovaza | Active comparator | Drug: omega-3-acid ethyl esters |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Subject candidates must fulfill all of the following inclusion criteria to be eligible for participation in the study:
- Healthy adult male and/or females, 18 to 55 years of age (inclusive).
- Body mass index (BMI) ≥ 18 and ≤ 29.9 (kg/m2).
- Medically healthy with clinically insignificant screening results. Hemoglobin must be ≥ the lower limit of normal.
- Non-tobacco/nicotine-containing product users for a minimum of 6 months prior to dosing.
Key exclusion criteria (28 listed)
- Subjects may be excluded from the study if there is evidence of any of the following criteria at screening, check-in, or at any time during the study as appropriate.
- For both arms (Warfarin and Epanova, Lovaza)
- Has a history or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal (GI), endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
- Has a positive urine drug/alcohol testing at screening or check-in.
- Has a positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
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 |
|---|---|---|
| warfarinAlso: coumarin-based anticoagulantA single 25 mg dose of warfarin | Drug | Warfarin and Epanova |
| omefasAlso: Epanova4 x 1 g capsule dose of Epanova® | Drug | Warfarin and Epanova |
| omega-3-acid ethyl estersAlso: Lovaza4 x 1 g capsule dose of Lovaza® | Drug | Lovaza |
Primary outcome
Pharmacokinetics of R- and S- warfarin
Time frame: 168 hours
The primary endpoints of this study will be the area under the curve (AUC)0-t, AUC0-inf, and maximum concentration (Cmax) of R- and S warfarin and the maximum International Normalized Ratio (INRmax) over 168 hours postdose and INR AUC0-168 when warfarin is administered with and without Epanova®.
Pharmacodynamics of R- and S- warfarin
Time frame: 168 hours
The INRmax over 168 hours postdose and INR AUC0-168 when warfarin is administered with and without Epanova®.
1 secondary outcome
Total EPA+DHA
Time frame: 24 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2015.
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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.
Michael H Davidson, MD, FACC study director
Omthera Pharmaceuticals, Inc
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 warfarin, omefas and omega-3-acid ethyl esters in people with Hypertriglyceridemia, run by AstraZeneca 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 8 inclusion and 28 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 24 Apr 2015. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Pharmacokinetics of R- and S- warfarin (time frame: 168 hours). The study lists 2 primary outcomes in all. 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 24 Apr 2015.