An Open-Label Crossover Study to Compare the Relative Bioavailability, Efficacy and Safety of Epanova® and Lovaza® in Men and Women With a History of Pancreatitis (ECLIPSEIV)

A Randomized, Open-Label Crossover Study to Compare the Relative Bioavailability, Efficacy, and Safety of Epanova® and Lovaza® in Men and Women With a History of Pancreatitis

This is a randomized, open-label crossover study. The primary objective of this study is to compare the relative bioavailability of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and the ethyl esters of EPA and DHA in plasma from a single 2 g or 4 g dose of Epanova® or 4 g Lovaza®.

Study Overview

• Status: Completed
• Conditions: Severe Hypertriglyceridemia
• Intervention / Treatment: Drug: Epanova; Drug: Lovaza

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Chocoutimi, Quebec, Canada
      • Research Site
• United States
  • Kansas
    • Kansas City, Kansas, United States
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female, ≥18 years of age;
2. History of serum TG concentration ≥500 mg/dL within the past 5 years;
3. Have at least one episode of documented hospitalization for pancreatitis due to hypertriglyceridemia in his/her lifetime;
4. Have no health conditions that would prevent him/her from fulfilling the study requirements as judged by the Investigator on the basis of physical examination, ECG, medical history, and routine laboratory test results;
5. Willing to maintain his/her current activity level and to follow either the NCEP TLC diet with a caloric target for weight maintenance or a prescribed low-fat diet during the screening, treatment, and washout periods (Visits 1 through 6b; Weeks -4 through 12);
6. Willing to eat the standardized breakfast, lunch, and dinner meals and snacks before and during Visits 4b and 6b (Weeks 4 and 12);
7. Willing to abstain from alcohol consumption and avoid vigorous physical activity for 48 hours prior to Visits 3 through 6b (Weeks 0 through 12); and
8. Subject understands the study procedures and is willing and able to sign the informed consent form to participate in the study and the Health Insurance Portability and Accountability Act authorization for release of relevant protected health information to the Investigators and study personnel.

Exclusion Criteria:

1. An allergy or intolerance to omega-3 fatty acids, omega-3-acid ethyl esters, fish, or any of the components of the standardized breakfast, lunch, or dinner meals or snacks (as described to them by study staff)
2. Poorly controlled hypertension (resting blood pressure ≥160 mmHg systolic and/or ≥100 mmHg diastolic) prior to randomization (Visit 3 [Week 0])
3. A history of cancer (other than basal cell carcinoma) in the last 2 years
4. A recent cardiovascular event (i.e., myocardial infarction, acute coronary syndrome, new onset angina, stroke, transient ischemic attack, unstable congestive heart failure requiring a change in treatment), aortic aneurysm or resection, carotid endarterectomy, or revascularization procedure within the 6 months prior to Visit 1

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: E4:L4; Crossover Sequence	Drug: Epanova; Drug: Lovaza
Active Comparator: L4:E4; Crossover Sequence	Drug: Epanova; Drug: Lovaza
Active Comparator: E2:L4; Crossover Sequence	Drug: Epanova; Drug: Lovaza
Active Comparator: L4:E2; Crossover Sequence	Drug: Epanova; Drug: Lovaza

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline-adjusted AUC0-24 for Plasma Total EPA + Total DHA	AUC0-24: Area under the plasma concentration versus time curve, from time 0 to 24 hours after start of the meal	participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between.
Baseline-adjusted Cmax for Plasma Total EPA + Total DHA	Cmax: Maximum measured plasma concentration over the time span specified	participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between.

Secondary Outcome Measures

Outcome Measure	Time Frame
Baseline-adjusted AUC0-24 for Plasma Total EPA	participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between.
Baseline-adjusted Cmax for Plasma Total EPA	participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between.
Baseline-adjusted AUC0-24 for Plasma Total DHA	participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between.
Baseline-adjusted Cmax for Plasma Total DHA	This is a crossover study with two treatment periods. The estimated treatment effects were based on the within-subject comparison between the two treatments, each having a 4-week duration and a 4-week wash off period in between.
Baseline-adjusted AUC0-24 for Plasma Total DPA	participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between.
Baseline-adjusted Cmax for Plasma Total DPA	participants were followed for the duration of study, up to 12 weeks, each treatment having a 4-week duration and a 4-week wash off period in between.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Andrea L Lawless, MD, Biofortis, Inc Addison IL 60101

Publications and helpful links

General Publications

• Dunbar RL, Gaudet D, Davidson M, Rensfeldt M, Yang H, Nilsson C, Kvarnstrom M, Oscarsson J. Omega-3 fatty acid exposure with a low-fat diet in patients with past hypertriglyceridemia-induced acute pancreatitis; an exploratory, randomized, open-label crossover study. Lipids Health Dis. 2020 May 30;19(1):117. doi: 10.1186/s12944-020-01295-7.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: June 23, 2014
• First Submitted That Met QC Criteria: July 11, 2014
• First Posted (Estimate): July 14, 2014

Study Record Updates

• Last Update Posted (Estimate): June 20, 2016
• Last Update Submitted That Met QC Criteria: May 11, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Pancreatic Diseases; Pancreatitis; Hypertriglyceridemia
• Other Study ID Numbers: D5880C00003; OM-EPA-013 (Other Identifier: Omthera)