Non-alcoholic Fatty Liver Disease (NAFLD, Hypertriglyceridemia
Conditions
Keywords
omega-3 carboxylic acid
Brief summary
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.
Interventions
DRUGPlacebo
Placebo matching to Omega-3 carboxylic acids (olive oil)
DRUGOmega-3 carboxylic acid
4 g administered as 4 x 1 g capsules
200mg capsule administered once daily
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Ratio (Week 12/Baseline) of % Liver Fat as Assessed by MRI (Epanova Versus Placebo) | Baseline and 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Ratio (Week 12/Baseline) of % Liver Fat as Assessed by MRI (Epanova Versus Fenofibrate) | 12 weeks | 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. |
Countries
Sweden
Participant flow
Recruitment details
This study was conducted in 4 centers in Sweden between 01 September 2015 and 26 May 2016.
Pre-assignment details
The study duration was up to 15 weeks, consisting of an initial screening period lasting up to 2 weeks, a 12-week treatment period, and a follow-up telephone call within 1 week after the last dose of study drug. A total of 78 subjects were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Epanova Epanova 4 g/day + placebo to Fenofibrate | 25 |
| Fenofibrate Fenofibrate 200 mg/ day + placebo to Epanova | 27 |
| Placebo Placebo to Epanova + placebo to Fenofibrate | 26 |
| Total | 78 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 2 |
| Overall Study | Other - reason not specified | 1 | 0 | 1 |
| Overall Study | Study-specifc withdrawal criteria | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Epanova | Fenofibrate | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 60.0 Years STANDARD_DEVIATION 7.79 | 61.7 Years STANDARD_DEVIATION 7.78 | 60.8 Years STANDARD_DEVIATION 7.85 | 60.8 Years STANDARD_DEVIATION 7.73 |
| Age, Customized <50 | 3 Participants | 3 Participants | 1 Participants | 7 Participants |
| Age, Customized >=50 - <65 | 16 Participants | 14 Participants | 15 Participants | 45 Participants |
| Age, Customized >=65 | 6 Participants | 10 Participants | 10 Participants | 26 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 23 Participants | 26 Participants | 26 Participants | 75 Participants |
| Sex/Gender, Customized Female | 9 Participants | 12 Participants | 12 Participants | 33 Participants |
| Sex/Gender, Customized Male | 16 Participants | 15 Participants | 14 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 25 | 15 / 27 | 8 / 26 |
| serious Total, serious adverse events | 1 / 25 | 0 / 27 | 0 / 26 |
Outcome results
Primary
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.
Time frame: Baseline and 12 weeks
Population: The Full Analysis Set included all randomized patients, regardless of whether they took study medication or not. In this set, patients were analyzed according to their randomized treatment assignment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Epanova | Geometric Mean Ratio (Week 12/Baseline) of % Liver Fat as Assessed by MRI (Epanova Versus Placebo) | 0.98 ratio of % liver fat |
| Placebo | Geometric Mean Ratio (Week 12/Baseline) of % Liver Fat as Assessed by MRI (Epanova Versus Placebo) | 1.04 ratio of % liver fat |
p-value: 0.40795% CI: [0.76, 1.12]Mixed Models Analysis
Secondary
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.
Time frame: 12 weeks
Population: The Full Analysis Set included all randomized patients, regardless of whether they took study medication or not. In this set, patients were analyzed according to their randomized treatment assignment.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Epanova | Geometric Mean Ratio (Week 12/Baseline) of % Liver Fat as Assessed by MRI (Epanova Versus Fenofibrate) | 0.98 ratio of % liver fat |
| Placebo | Geometric Mean Ratio (Week 12/Baseline) of % Liver Fat as Assessed by MRI (Epanova Versus Fenofibrate) | 1.17 ratio of % liver fat |
p-value: 0.07795% CI: [0.7, 1.02]Mixed Models Analysis