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

NCT01431690 | Completed Phase 1

• 1 other identifier: OM-EPA-006
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief 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 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

Keywords

Eicosapentaenoic Acid; Docosahexaenoic Acid; Warfarin; Hypertriglyceridemia; Omega-3 free fatty acids; Omega-3 ethyl ester acids; Epanova; Lovaza; pharmacokinetics; low-fat meal

Outcome Measures

Primary Outcomes (2)

• 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®.

  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®.

  168 hours

Secondary Outcomes (1)

• Total EPA+DHA

  24 hours

Study Arms (2)

Warfarin and Epanova

EXPERIMENTAL

Drug: warfarin; Drug: omefas

Lovaza

ACTIVE COMPARATOR

Drug: omega-3-acid ethyl esters

Interventions

warfarin DRUG

A single 25 mg dose of warfarin

Also known as: coumarin-based anticoagulant

Warfarin and Epanova

omefas DRUG

4 x 1 g capsule dose of Epanova®

Also known as: Epanova

Warfarin and Epanova

omega-3-acid ethyl esters DRUG

4 x 1 g capsule dose of Lovaza®

Also known as: Lovaza

Lovaza

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Unknown Facility

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Conditions

Hypertriglyceridemia

Interventions

Warfarin; Omacor

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Michael H Davidson, MD, FACC

  Omthera Pharmaceuticals, Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2011
• First Posted: September 9, 2011
• Study Start: August 1, 2011
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: April 24, 2015

Record last verified: 2015-04

Locations

US (1)