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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Omthera Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT01486433
First received: November 29, 2011
Last updated: April 27, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Hypertriglyceridemia
Drug: Simvastatin
Drug: acetylsalicylic acid (ASA)
Drug: omefas
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Randomized, 2-Way Crossover Study to Evaluate the Effect of Multiple Doses of Epanova® on the Multiple-Dose Pharmacokinetics of Simvastatin in Healthy Normal Subjects

Resource links provided by NLM:


Further study details as provided by Omthera Pharmaceuticals, Inc:

Primary Outcome Measures:
  • Area under the plasma concentration versus time curve (AUC0-tau) [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
    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

  • Concentration at the end of a dosing interval (Cmax,ss) for simvastatin and beta- hydroxysimvastatin acid, [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 52
Study Start Date: November 2011
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Epanova and Simvastatin Drug: Simvastatin
40 mg (1 tablet) simvastatin once a day
Drug: acetylsalicylic acid (ASA)
81 mg aspirin (1 tablet), once a day, co-administered with simvastatin
Other Name: aspirin
Drug: omefas
4 g (4 capsules) Epanova once a day, co-administered with simvastatin and aspirin
Other Name: Epanova
Active Comparator: Simvastatin Drug: Simvastatin
40 mg (1 tablet) simvastatin once a day
Drug: acetylsalicylic acid (ASA)
81 mg aspirin (1 tablet), once a day, co-administered with simvastatin
Other Name: aspirin

Detailed Description:

The study is testing the hypothesis that there is no interaction between Epanova and concomitant administration of simvastatin and aspirin. No drug interaction will be claimed if, following concomitant administration of simvastatin, aspirin and Epanova or only simvastatin and aspirin, the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of the back-transformed PK parameters, area under the plasma concentration versus time curve (AUC0-tau) and concentration at the end of a dosing interval (Cmax,ss), for simvastatin and beta- hydroxysimvastatin acid,fall within 80%-125%.

  Eligibility

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

Inclusion Criteria:

Subjects must fulfil all of the following inclusion criteria to be eligible for participation in the study, unless otherwise specified:

  1. Healthy adult male or female volunteers, 18-55 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. Continuous non-smokers who haven't used nicotine-containing products for at least 6 months prior to the first dose.
  5. Voluntarily consent to participate in the study and to follow the restrictions and procedures outlined for the study.
  6. 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.

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:

  1. 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.
  2. 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.
  3. Positive urine drug/alcohol testing at screening or check-in.
  4. Positive result for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
  5. History or presence of alcoholism or drug abuse within the past 2 years.
  6. 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.
  7. Known sensitivity or allergy to soybeans, fish, and/or shellfish.
  8. Hypersensitivity or idiosyncratic reaction to compounds related to simvastatin (i.e., HMG-CoA reductase inhibitors) and/or Epanova® and/or aspirin.
  9. Subject is a female who is pregnant or lactating.
  10. Use of any prescription medication within 14 days prior to the first dose.
  11. 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.
  12. 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.
  13. Donation of blood or significant blood loss within 56 days prior to check- in.
  14. Donation of plasma within 7 days prior to check-in.
  15. Participation in another clinical trial within 30 days prior to 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: NCT01486433

Locations
United States, Arizona
Tempe, Arizona, United States, 85263
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: NCT01486433     History of Changes
Other Study ID Numbers: OM-EPA-007
Study First Received: November 29, 2011
Last Updated: April 27, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Omthera Pharmaceuticals, Inc:
eicosapentaenoic acid
docosapentaenoic acid
arachidonic acid
hypertriglyceridemia
simvastatin

Additional relevant MeSH terms:
Hypertriglyceridemia
Dyslipidemias
Hyperlipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Aspirin
Simvastatin
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Anticholesteremic Agents
Antimetabolites
Antipyretics
Antirheumatic Agents
Cardiovascular Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors

ClinicalTrials.gov processed this record on October 30, 2014