The Effect of Multiple Doses of Epanova® on the Multiple-Dose Pharmacokinetics of Simvastatin in Healthy Normal Subjects
Primary Purpose
Hypertriglyceridemia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Simvastatin
acetylsalicylic acid (ASA)
omefas
Sponsored by

About this trial
This is an interventional treatment trial for Hypertriglyceridemia focused on measuring eicosapentaenoic acid, docosapentaenoic acid, arachidonic acid, hypertriglyceridemia, simvastatin
Eligibility Criteria
Inclusion Criteria:
Subjects must fulfil all of the following inclusion criteria to be eligible for participation in the study, unless otherwise specified:
- 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.
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:
- 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.
- Participation in another clinical trial within 30 days prior to check-in.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Epanova and Simvastatin
Simvastatin
Arm Description
Outcomes
Primary Outcome Measures
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
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.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01486433
Brief Title
The Effect of Multiple Doses of Epanova® on the Multiple-Dose Pharmacokinetics of Simvastatin in Healthy Normal Subjects
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
November 2011 (undefined)
Primary Completion Date
March 2012 (Actual)
Study Completion Date
March 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
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%.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertriglyceridemia
Keywords
eicosapentaenoic acid, docosapentaenoic acid, arachidonic acid, hypertriglyceridemia, simvastatin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
52 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Epanova and Simvastatin
Arm Type
Experimental
Arm Title
Simvastatin
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Simvastatin
Intervention Description
40 mg (1 tablet) simvastatin once a day
Intervention Type
Drug
Intervention Name(s)
acetylsalicylic acid (ASA)
Other Intervention Name(s)
aspirin
Intervention Description
81 mg aspirin (1 tablet), once a day, co-administered with simvastatin
Intervention Type
Drug
Intervention Name(s)
omefas
Other Intervention Name(s)
Epanova
Intervention Description
4 g (4 capsules) Epanova once a day, co-administered with simvastatin and aspirin
Primary Outcome Measure Information:
Title
Area under the plasma concentration versus time curve (AUC0-tau)
Description
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
Time Frame
14 days
Title
Concentration at the end of a dosing interval (Cmax,ss) for simvastatin and beta- hydroxysimvastatin acid,
Description
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.
Time Frame
14 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Subjects must fulfil all of the following inclusion criteria to be eligible for participation in the study, unless otherwise specified:
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.
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:
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.
Participation in another clinical trial within 30 days prior to check-in.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael H Davidson, MD, FACC
Organizational Affiliation
Omthera Pharmaceuticals, Inc
Official's Role
Study Director
Facility Information:
City
Tempe
State/Province
Arizona
ZIP/Postal Code
85263
Country
United States
12. IPD Sharing Statement
Learn more about this trial
The Effect of Multiple Doses of Epanova® on the Multiple-Dose Pharmacokinetics of Simvastatin in Healthy Normal Subjects
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