The Effect of Multiple Doses of Epanova® on the Multiple-Dose Pharmacokinetics of Simvastatin in Healthy Normal Subjects

NCT01486433 | Completed Phase 1

• 1 other identifier: OM-EPA-007
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective is to determine the effect of multiple doses of Epanova® (omega fatty acids) on the pharmacokinetics (PK) of multiple 40 mg doses of simvastatin.

Conditions

Hypertriglyceridemia

Keywords

eicosapentaenoic acid; docosapentaenoic acid; arachidonic acid; hypertriglyceridemia; simvastatin

Outcome Measures

Primary Outcomes (2)

• Area under the plasma concentration versus time curve (AUC0-tau)

  Area under the plasma concentration versus time curve (AUC0-tau)for simvastatin and beta- hydroxysimvastatin acid, measured over the 24 hour period after the 14th dose

  14 days

• Concentration at the end of a dosing interval (Cmax,ss) for simvastatin and beta- hydroxysimvastatin acid,

  Maximum measured plasma concentration for simvastatin and beta- hydroxysimvastatin acid,during the 0-24 hour dosing interval for the 14th simvastatin dose (Day 14)measured over the 24 hour period after the 14th dose.

  14 days

Study Arms (2)

Epanova and Simvastatin

EXPERIMENTAL

Drug: Simvastatin; Drug: acetylsalicylic acid (ASA); Drug: omefas

Simvastatin

ACTIVE COMPARATOR

Drug: Simvastatin; Drug: acetylsalicylic acid (ASA)

Interventions

Simvastatin DRUG

40 mg (1 tablet) simvastatin once a day

Epanova and Simvastatin; Simvastatin

acetylsalicylic acid (ASA) DRUG

81 mg aspirin (1 tablet), once a day, co-administered with simvastatin

Also known as: aspirin

Epanova and Simvastatin; Simvastatin

omefas DRUG

4 g (4 capsules) Epanova once a day, co-administered with simvastatin and aspirin

Also known as: Epanova

Epanova and Simvastatin

Eligibility Criteria

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

You may qualify if:

• Healthy adult male or female volunteers, 18-55 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.
• Continuous non-smokers who haven't used nicotine-containing products for at least 6 months prior to the first dose.
• Voluntarily consent to participate in the study and to follow the restrictions and procedures outlined for the study.
• Females must be of non-childbearing potential, and have undergone sterilization procedures at least 6 months prior to the first dose or be postmenopausal with amenorrhea for at least 2 years prior to first dosing and follicle stimulating hormone (FSH) serum levels ≥ 40 mIU/mL.

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:
• History or presence of significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal (GI), endocrine, immunologic, dermatologic, neurological, or psychiatric disease in the opinion of the PI.
• 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.
• Positive urine drug/alcohol testing at screening or check-in.
• Positive result for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
• History or presence of alcoholism or drug abuse within the past 2 years.
• Subject has been on a special diet (for whatever reason) within the 28 days prior to the assigned first dose of study drug or anytime during the study.
• Known sensitivity or allergy to soybeans, fish, and/or shellfish.
• Hypersensitivity or idiosyncratic reaction to compounds related to simvastatin (i.e., HMG-CoA reductase inhibitors) and/or Epanova® and/or aspirin.
• Subject is a female who is pregnant or lactating.
• Use of any prescription medication within 14 days prior to the first dose.
• Use of any over-the-counter (OTC) medication, including herbal products (e.g., bromelains, danshen, dong quai \[Angelica sinensis\], garlic, ginko biloba, ginseng, and St. John's wort, NSAIDs), vitamin K or food supplements (especially omega-3-fatty acids) within the 7 days prior to first dosing.
• Use of 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.
• Donation of blood or significant blood loss within 56 days prior to check- in.
• Donation of plasma within 7 days prior to check-in.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Unknown Facility

Tempe, Arizona, 85263, United States

Location

MeSH Terms

Conditions

Hypertriglyceridemia

Interventions

Simvastatin; Aspirin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives

Study Officials

• Michael H Davidson, MD, FACC

  Omthera Pharmaceuticals, Inc

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: November 29, 2011
• First Posted: December 6, 2011
• Study Start: November 1, 2011
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: April 30, 2015

Record last verified: 2015-04

Locations

US (1)