Study to Evaluate the 2-Way Interaction Between Multiple Doses of Epanova™ and a Single Dose of Rosuvastatin (Crestor®)

Study Overview
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Brief Summary
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This study is intended to evaluate the potential 2-way reciprocal interaction between multiple doses of Epanova™ and a single dose of rosuvastatin

Detailed Description
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The PK of rosuvastatin will be monitored following single-dose administration of rosuvastatin with and without multiple-dose administration of 4 g Epanova™ for 13 consecutive days in order to detect a possible interaction between rosuvastatin and Epanova™. The PK of total EPA, total DHA and total EPA+DHA will also be monitored following multiple-dose administration of Epanova™ with and without single-dose administration of 40 mg rosuvastatin. A single dose administration for rosuvastatin has been judged sufficient to yield plasma concentrations that will be detectable with an adequate validated analytical method and characterize adequately the PK of rosuvastatin.

Official Title
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An Open-Label, 2-Cohort Study to Evaluate the 2-Way Interaction Between Multiple Doses of Epanova™ and a Single Dose of Rosuvastatin (Crestor®), to Assess the Dose Proportionality of Epanova™, and to Compare the Systemic Exposure of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) Following Multiple Doses of Epanova™ and Vascepa® in Healthy Normal Subjects

Conditions
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Hypertriglyceridemia

Intervention / Treatment
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* Drug: rosuvastatin 40 mg tablet
* Drug: Epanova™ QD (2 x 1 g capsules)
* Drug: Multiple doses of 4 g Epanova™ with single of rosuvastatin 40 mg dose
* Drug: Multiple (20) oral doses of 2 g Vascepa® every 12 hours


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female (non-childbearing potential) Body Mass Index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2 at screening Non-smoker Medically healthy with no clinically significant laboratory profiles, vital signs or ECGs Exclusion Criteria: mentally or legally incapacitated or has significant emotional problems at the time of screening visit or expected during the conduct of the study History or presence of myopathy and/or hypothyroidism. History or presence of transaminase elevations History or presence of hypersensitivity or idiosyncratic reaction to rosuvastatin, to other HMG-CoA reductase inhibitors, to Epanova™, to Vascepa®, or to related compounds Known sensitivity or allergy to soybeans, fish, and/or shellfish. Has consumed fish within 7 days prior to check-in. Female subjects who are pregnant or lactating. Positive urine drug and alcohol results at screening or check-in. Positive urine cotinine at screening and check-in Use of any drugs known to be inducers of CYP enzymes and/or P-gp Donation of blood or significant blood loss within 56 days prior to the first dose of study medication. Plasma donation within 7 days prior to the first dose of study medication. Participation in another clinical trial within 28 days prior to the first dose of study medication.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rosuvastatin<br>Single oral dose of 40 mg (1 x 40 mg tablet) rosuvastatin (Crestor®) (Day 1). | Drug: rosuvastatin 40 mg tablet<br>* Single oral dose of 40 mg (1 x 40 mg tablet) rosuvastatin (Crestor®) (Day 1).<br>* Other names: Crestor;|
| Experimental: Epanova®<br>Multiple oral doses of 2 g (2 x 1 g capsules) Epanova® QD for 10 consecutive days (Days 4 to 13) | Drug: Epanova™ QD (2 x 1 g capsules)<br>* Multiple oral doses of 2 g (2 x 1 g capsules) Epanova™ QD for 10 consecutive days (Days 4 to 13)<br>* Other names: omega-3 carboxylic acids;|
| Experimental: Epanova® + Crestor®<br>Epanova® multiple oral doses of 4 g (4 x 1 g capsules) QD for 13 consecutive days (Days 14 to 26) with coadministration of single 40 mg (1 x 40 mg tablet) oral dose of rosuvastatin (Crestor®) with the 11th dose of 4 g Epanova® on Day 24 | Drug: Multiple doses of 4 g Epanova™ with single of rosuvastatin 40 mg dose<br>* Multiple oral doses of 4 g Epanova™ QD for 13 consecutive days with coadministration of single 40 mg oral dose of rosuvastatin (Crestor®) with the 11th dose of Epanova™ on Day 24<br>* Other names: Crestor;|
| Active Comparator: Vascepa®<br>Vascepa® multiple oral doses of 2 g (2 x 1 g capsules) every 12 hours for 20 consecutive days (Days 1 to 20). | Drug: Multiple (20) oral doses of 2 g Vascepa® every 12 hours<br>* Multiple oral doses of 2 g (2 x 1 g capsules) Vascepa® every 12 hours for 20 consecutive days (Days 1 to 20).<br>* Other names: icosapent ethyl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ln-transformed Cmax,ss of baseline-adjusted total EPA, total DHA, and total EPA+DHA | ln-transformed Cmax,ss of baseline-adjusted (primary analysis) and unadjusted (secondary analysis) total EPA, total DHA, and total EPA+DHA using a linear mixed effect model. | Days 1 and 24 | 
| ln-transformed AUC0-tau of baseline-adjusted total EPA, total DHA, and total EPA+DHA | ln-transformed AUC0-tau of baseline-adjusted (primary analysis) and unadjusted (secondary analysis) total EPA, total DHA, and total EPA+DHA using a linear mixed effect model. | Days 1 and 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ln-transformed Cmax,ss of unadjusted total EPA, total DHA, and total EPA+DHA | ln-transformed Cmax,ss of baseline-adjusted (primary analysis) and unadjusted (secondary analysis) total EPA, total DHA, and total EPA+DHA using a linear mixed effect model. | Days 1 and 24 | 
| dose proportionality of baseline-adjusted total EPA, total DHA, and total EPA+DHA systemic exposure will be assessed following multiple doses of Epanova™ 2 g and 4 g | In Cohort 1 only, dose proportionality of baseline-adjusted total EPA, total DHA, and total EPA+DHA systemic exposure will be assessed following multiple doses of Epanova™ 2 g and 4 g using an analysis of variance (ANOVA) on dose normalized data. | Days 1 and 24 | 
| ln-transformed AUC0-tau of unadjusted total EPA, total DHA, and total EPA+DHA | ln-transformed AUC0-tau of baseline-adjusted (primary analysis) and unadjusted (secondary analysis) total EPA, total DHA, and total EPA+DHA using a linear mixed effect model. | Days 1 and 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epanova, omega-3 carboxylic acids, Vascepa, Eicosapentaenoic acid ethyl ester, Crestor, rosuvastatin