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

Primary Purpose

Hypertriglyceridemia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
rosuvastatin 40 mg tablet
Epanova™ QD (2 x 1 g capsules)
Multiple doses of 4 g Epanova™ with single of rosuvastatin 40 mg dose
Multiple (20) oral doses of 2 g Vascepa® every 12 hours
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypertriglyceridemia focused on measuring Epanova, omega-3 carboxylic acids, Vascepa, Eicosapentaenoic acid ethyl ester, Crestor, rosuvastatin

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Celerion

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Arm Label

Rosuvastatin

Epanova®

Epanova® + Crestor®

Vascepa®

Arm Description

Single oral dose of 40 mg (1 x 40 mg tablet) rosuvastatin (Crestor®) (Day 1).

Multiple oral doses of 2 g (2 x 1 g capsules) Epanova® QD for 10 consecutive days (Days 4 to 13)

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

Vascepa® multiple oral doses of 2 g (2 x 1 g capsules) every 12 hours for 20 consecutive days (Days 1 to 20).

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
July 18, 2016
Last Updated
August 16, 2016
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT02859129
Brief Title
Study to Evaluate the 2-Way Interaction Between Multiple Doses of Epanova™ and a Single Dose of Rosuvastatin (Crestor®)
Acronym
ECLIPSEIII
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
September 2013 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
November 2013 (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
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertriglyceridemia
Keywords
Epanova, omega-3 carboxylic acids, Vascepa, Eicosapentaenoic acid ethyl ester, Crestor, rosuvastatin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
114 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rosuvastatin
Arm Type
Experimental
Arm Description
Single oral dose of 40 mg (1 x 40 mg tablet) rosuvastatin (Crestor®) (Day 1).
Arm Title
Epanova®
Arm Type
Experimental
Arm Description
Multiple oral doses of 2 g (2 x 1 g capsules) Epanova® QD for 10 consecutive days (Days 4 to 13)
Arm Title
Epanova® + Crestor®
Arm Type
Experimental
Arm Description
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
Arm Title
Vascepa®
Arm Type
Active Comparator
Arm Description
Vascepa® multiple oral doses of 2 g (2 x 1 g capsules) every 12 hours for 20 consecutive days (Days 1 to 20).
Intervention Type
Drug
Intervention Name(s)
rosuvastatin 40 mg tablet
Other Intervention Name(s)
Crestor
Intervention Description
Single oral dose of 40 mg (1 x 40 mg tablet) rosuvastatin (Crestor®) (Day 1).
Intervention Type
Drug
Intervention Name(s)
Epanova™ QD (2 x 1 g capsules)
Other Intervention Name(s)
omega-3 carboxylic acids
Intervention Description
Multiple oral doses of 2 g (2 x 1 g capsules) Epanova™ QD for 10 consecutive days (Days 4 to 13)
Intervention Type
Drug
Intervention Name(s)
Multiple doses of 4 g Epanova™ with single of rosuvastatin 40 mg dose
Other Intervention Name(s)
omega-3 carboxylic acids, Crestor
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Multiple (20) oral doses of 2 g Vascepa® every 12 hours
Other Intervention Name(s)
icosapent ethyl
Intervention Description
Multiple oral doses of 2 g (2 x 1 g capsules) Vascepa® every 12 hours for 20 consecutive days (Days 1 to 20).
Primary Outcome Measure Information:
Title
ln-transformed Cmax,ss of baseline-adjusted total EPA, total DHA, and total EPA+DHA
Description
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.
Time Frame
Days 1 and 24
Title
ln-transformed AUC0-tau of baseline-adjusted total EPA, total DHA, and total EPA+DHA
Description
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.
Time Frame
Days 1 and 24
Secondary Outcome Measure Information:
Title
ln-transformed Cmax,ss of unadjusted total EPA, total DHA, and total EPA+DHA
Description
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.
Time Frame
Days 1 and 24
Title
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
Description
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.
Time Frame
Days 1 and 24
Title
ln-transformed AUC0-tau of unadjusted total EPA, total DHA, and total EPA+DHA
Description
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.
Time Frame
Days 1 and 24
Other Pre-specified Outcome Measures:
Title
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®
Description
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.
Time Frame
Days 1 and 24
Title
AEs, vital signs, ECG, laboratory tests
Description
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).
Time Frame
through study completion (14 days)
Title
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®
Description
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.
Time Frame
Days 1 and 24
Title
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®
Description
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.
Time Frame
Days 1 and 24

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: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael D Davidson, MD
Organizational Affiliation
Omthera Pharmaceuticals/AstraZeneca
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Sandra M Connolly, MD
Organizational Affiliation
Celerion
Official's Role
Principal Investigator
Facility Information:
Facility Name
Celerion
City
Neptune
State/Province
New Jersey
ZIP/Postal Code
07753
Country
United States

12. IPD Sharing Statement

Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=4425&filename=OMA_EPA_009_CSR.pdf
Description
CSR Synopsis

Learn more about this trial

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

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