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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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Omthera Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT01431690
First received: September 8, 2011
Last updated: January 6, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Hypertriglyceridemia
Drug: warfarin
Drug: omefas
Drug: omega-3-acid ethyl esters
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Omthera Pharmaceuticals, Inc:

Primary Outcome Measures:
  • Pharmacokinetics of R- and S- warfarin [ Time Frame: 168 hours ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    The INRmax over 168 hours postdose and INR AUC0-168 when warfarin is administered with and without Epanova®.


Secondary Outcome Measures:
  • Total EPA+DHA [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    The AUC0-tau and Cmax of baseline-adjusted total EPA+DHA following multiple doses (14 days) of Epanova® and Lovaza®.


Enrollment: 52
Study Start Date: August 2011
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Warfarin and Epanova Drug: warfarin
A single 25 mg dose of warfarin
Other Name: coumarin-based anticoagulant
Drug: omefas
4 x 1 g capsule dose of Epanova®
Other Name: Epanova
Active Comparator: Lovaza Drug: omega-3-acid ethyl esters
4 x 1 g capsule dose of Lovaza®
Other Name: Lovaza

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Subject candidates must fulfill all of the following inclusion criteria to be eligible for participation in the study:

  1. Healthy adult male and/or females, 18 to 55 years of age (inclusive).
  2. Body mass index (BMI) ≥ 18 and ≤ 29.9 (kg/m2).
  3. Medically healthy with clinically insignificant screening results. Hemoglobin must be ≥ the lower limit of normal.
  4. Non-tobacco/nicotine-containing product users for a minimum of 6 months prior to dosing.
  5. Voluntarily consent to participate in the study and to follow the restrictions and procedures outlined for the study.
  6. 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.
  7. 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.

Exclusion Criteria:

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)

  1. Has a history or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal (GI), endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
  2. Has a positive urine drug/alcohol testing at screening or check-in.
  3. Has a positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
  4. Has consumed fish within 7 days prior to check-in.
  5. Has used fish oil, other EPA and/or DHA containing supplements within 2 months of check-in.
  6. Has a history or presence of alcoholism or drug abuse within the 2 years prior to check-in.
  7. Has a known sensitivity or allergy to soybeans, fish, and/or shellfish.
  8. Has had a hypersensitivity or idiosyncratic reaction to compounds related to Epanova® and Lovaza®.
  9. Has used any prescription medication (with the exception of hormonal contraceptives for females in the Lovaza arm) within 14 days prior to check-in.
  10. 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.
  11. 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.
  12. Has donated blood or has had a significant blood loss within 56 days prior to check-in.
  13. Has donated plasma within 7 days prior to check-in.
  14. Has participated in another clinical trial within 30 days prior to check-in.
  15. Is a female who is pregnant or lactating.

For Warfarin and Epanova Arm only:

  1. 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.
  2. 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).
  3. 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.
  4. Has active severe gingivitis.
  5. Has had a hypersensitivity or idiosyncratic reaction to compounds related to warfarin.
  6. Has a recent physical injury (within the 2 weeks prior to screening).
  7. Has had a major surgery within the 3 months prior to screening.
  8. Is allergic to Vitamin K.
  9. Has used non-steroidal anti-inflammatory (NSAID) drugs within the 2 weeks prior to check-in.
  10. Has a positive fecal occult blood sample at check-in.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01431690

Locations
United States, Arizona
Tempe, Arizona, United States, 85283
Sponsors and Collaborators
Omthera Pharmaceuticals, Inc
Investigators
Study Director: Michael H Davidson, MD, FACC Omthera Pharmaceuticals, Inc
  More Information

No publications provided

Responsible Party: Omthera Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT01431690     History of Changes
Other Study ID Numbers: OM-EPA-006
Study First Received: September 8, 2011
Last Updated: January 6, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Omthera Pharmaceuticals, Inc:
Eicosapentaenoic Acid
Docosahexaenoic Acid
Warfarin
Hypertriglyceridemia
Omega-3 free fatty acids
Omega-3 ethyl ester acids
Epanova
Lovaza
pharmacokinetics
low-fat meal

Additional relevant MeSH terms:
Hypertriglyceridemia
Dyslipidemias
Hyperlipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Anticoagulants
Warfarin
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014