A Double-blind Randomized Placebo-controlled Study Comparing Epanova and Fenofibrate on Liver Fat in Overweight Subjects.

A Double-blind Randomized Placebo-controlled, Parallel-group 12 Week Study to Investigate the Effects of Epanova® Compared to Placebo and Compared to Fenofibrate on Liver Fat Content in Hypertriglyceridemic overwEight subjeCTs; EFFECT I

This study is a double-blind randomized, placebo-controlled, parallel-group, 12 week study performed in 2 centres in Sweden to assess the effect of Omega-3 carboxylic acids and fenofibrate on liver fat measured with magnetic resonance imaging (MRI) in patients with over-weight and hypertriglyceridemia.

Study Overview

• Status: Completed
• Conditions: Hypertriglyceridemia; Non-alcoholic Fatty Liver Disease (NAFLD
• Intervention / Treatment: Drug: Placebo; Drug: Placebo; Drug: Omega-3 carboxylic acid; Drug: Fenofibrate 200mg

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Göteborg, Sweden, 413 45
    • Research Site
  • Malmö, Sweden, 205 02
    • Research Site
  • Stockholm, Sweden, 11324
    • Research Site
  • Uppsala, Sweden, 75237
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: - Provision of informed consent

• Men or women ≥40 years and ≤75 years with suitable veins for cannulation or repeated venepuncture
• Have serum triglycerides ≥1.7 mM
• Have liver fat content as assessed by MRI >5.5%

• Have a body mass index (BMI) >25 and ≤40 kg/m2

  , Exclusion Criteria: - History of or presence of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.

• Creatinine clearance <60 mL/min at screening (Cockcroft-Gault formula).
• Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN
• Total bilirubin >2.0 mg/dL (34.2 µmol/L)
• Type 2 diabetes, as defined by WHO criteria e.g. fasting plasma Glucose >7.0 mM or use of antidiabetic therapy
• Any clinically significant abnormalities in clinical chemistry, haematology or urinalysis results as judged by the investigator. This includes signs of liver disease other than NAFLD that motivates further investigations of treatment based on clinical judgement
• Recent history (past 12 months) of drug abuse or alcohol abuse. Alcohol abuse was to be defined as >14 drinks per week (1 drink = 35 cl beer, 14 cl wine, or 4 cl hard liquor) or as judged by the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Placebo matching to Omega-3 carboxylic acids (olive oil); Drug: Placebo; Placebo matching to fenofibrate 200mg
EXPERIMENTAL: Omega-3 carboxylic acids 4g / day	Drug: Omega-3 carboxylic acid; 4 g administered as 4 x 1 g capsules
ACTIVE_COMPARATOR: Fenofibrate 200mg	Drug: Fenofibrate 200mg; 200mg capsule administered once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Ratio (Week 12/Baseline) of % Liver Fat as Assessed by MRI (Epanova Versus Placebo)	To evaluate the efficacy of Epanova compared to placebo with respect to reduction in liver fat content (%) at the end of 12 weeks of double-blinded treatment.	Baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Ratio (Week 12/Baseline) of % Liver Fat as Assessed by MRI (Epanova Versus Fenofibrate)	To evaluate the efficacy of Epanova compared to Fenofibrate with respect to reduction in liver fat content (%) at the end of 12 weeks of double-blinded treatment.	12 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Lars Lind, Professor, Uppsala University Hospital. Uppsala Sweden

Publications and helpful links

General Publications

• Oscarsson J, Onnerhag K, Riserus U, Sunden M, Johansson L, Jansson PA, Moris L, Nilsson PM, Eriksson JW, Lind L. Effects of free omega-3 carboxylic acids and fenofibrate on liver fat content in patients with hypertriglyceridemia and non-alcoholic fatty liver disease: A double-blind, randomized, placebo-controlled study. J Clin Lipidol. 2018 Nov-Dec;12(6):1390-1403.e4. doi: 10.1016/j.jacl.2018.08.003. Epub 2018 Aug 10.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2015
• Primary Completion (ACTUAL): May 26, 2016
• Study Completion (ACTUAL): May 26, 2016

Study Registration Dates

• First Submitted: January 30, 2015
• First Submitted That Met QC Criteria: January 30, 2015
• First Posted (ESTIMATE): February 3, 2015

Study Record Updates

• Last Update Posted (ACTUAL): September 25, 2018
• Last Update Submitted That Met QC Criteria: September 24, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: omega-3 carboxylic acid
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Body Weight; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Liver Diseases; Fatty Liver; Overweight; Non-alcoholic Fatty Liver Disease; Hypertriglyceridemia; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Fenofibrate
• Other Study ID Numbers: D5881C00007