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

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

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

Study Overview

• Status: Completed
• Conditions: Hypertriglyceridemia
• Intervention / Treatment: 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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 114
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Neptune, New Jersey, United States, 07753
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rosuvastatin; Single oral dose of 40 mg (1 x 40 mg tablet) rosuvastatin (Crestor®) (Day 1).	Drug: rosuvastatin 40 mg tablet; Single oral dose of 40 mg (1 x 40 mg tablet) rosuvastatin (Crestor®) (Day 1).; Other Names: Crestor
Experimental: Epanova®; 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); Multiple oral doses of 2 g (2 x 1 g capsules) Epanova™ QD for 10 consecutive days (Days 4 to 13); Other Names: omega-3 carboxylic acids
Experimental: Epanova® + Crestor®; 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; 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; Other Names: Crestor; omega-3 carboxylic acids
Active Comparator: Vascepa®; 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; Multiple oral doses of 2 g (2 x 1 g capsules) Vascepa® every 12 hours for 20 consecutive days (Days 1 to 20).; Other Names: icosapent ethyl

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ln-transformed AUC0-24 exposure of baseline-adjusted (primary analysis) and unadjusted (secondary analysis) total EPA, total DHA, and total EPA+DHA following multiple doses of Epanova™ compared to multiple doses of Vascepa®	The systemic exposure of baseline-adjusted (primary analysis) and unadjusted (secondary analysis) total EPA, total DHA, and total EPA+DHA following multiple doses of Epanova™ compared to multiple doses of Vascepa® will be assessed by analyzing the ln-transformed AUC0-24. In addition to an ANOVA, an analysis of covariance (ANCOVA) including the baseline value as a covariate will be performed.	Days 1 and 24
AEs, vital signs, ECG, laboratory tests	all AEs, physical examinations, vital signs (heart rate, blood pressure, respiratory rate, and temperature), 12-lead ECGs, and laboratory safety tests (hematology, serum chemistry, coagulation, and urinalysis).	through study completion (14 days)
ln-transformed Cavg of baseline-adjusted (primary analysis) and unadjusted (secondary analysis) total EPA, total DHA, and total EPA+DHA following multiple doses of Epanova™ compared to multiple doses of Vascepa®	The systemic exposure of baseline-adjusted (primary analysis) and unadjusted (secondary analysis) total EPA, total DHA, and total EPA+DHA following multiple doses of Epanova™ compared to multiple doses of Vascepa® will be assessed by analyzing the ln-transformed Cavg. In addition to an ANOVA, an analysis of covariance (ANCOVA) including the baseline value as a covariate will be performed.	Days 1 and 24
ln-transformed Cmax,ss of baseline-adjusted (primary analysis) and unadjusted (secondary analysis) total EPA, total DHA, and total EPA+DHA following multiple doses of Epanova™ compared to multiple doses of Vascepa®	The systemic exposure of baseline-adjusted (primary analysis) and unadjusted (secondary analysis) total EPA, total DHA, and total EPA+DHA following multiple doses of Epanova™ compared to multiple doses of Vascepa® will be assessed by analyzing the ln-transformed Cmax,ss. In addition to an ANOVA, an analysis of covariance (ANCOVA) including the baseline value as a covariate will be performed.	Days 1 and 24

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Michael D Davidson, MD, Omthera Pharmaceuticals/AstraZeneca; Principal Investigator: Sandra M Connolly, MD, Celerion

Publications and helpful links

Helpful Links

• CSR Synopsis

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: July 18, 2016
• First Submitted That Met QC Criteria: August 3, 2016
• First Posted (Estimate): August 8, 2016

Study Record Updates

• Last Update Posted (Estimate): August 17, 2016
• Last Update Submitted That Met QC Criteria: August 16, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: rosuvastatin; Crestor; Vascepa; Epanova; omega-3 carboxylic acids; Eicosapentaenoic acid ethyl ester
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypertriglyceridemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Eicosapentaenoic acid ethyl ester
• Other Study ID Numbers: OM-EPA-009