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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator |
| |
| Omega-3 carboxylic acids 4g / day | Experimental |
| |
| Fenofibrate 200mg | Active Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Placebo matching to Omega-3 carboxylic acids (olive oil) |
| |
| 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 |
| 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 |
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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
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| Name | Affiliation | Role |
|---|---|---|
| Lars Lind, Professor | Uppsala University Hospital. Uppsala Sweden | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Gothenburg | 413 45 | Sweden | |||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30197273 | Derived | 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. |
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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.
This study was conducted in 4 centers in Sweden between 01 September 2015 and 26 May 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | Epanova | Epanova 4 g/day + placebo to Fenofibrate |
| FG001 | Fenofibrate | Fenofibrate 200 mg/ day + placebo to Epanova |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Omega-3 carboxylic acid |
| Drug |
4 g administered as 4 x 1 g capsules |
|
| Fenofibrate 200mg | Drug | 200mg capsule administered once daily |
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| Placebo | Drug | Placebo matching to fenofibrate 200mg |
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| Malmö |
| 205 02 |
| Sweden |
| Research Site | Stockholm | 11324 | Sweden |
| Research Site | Uppsala | 75237 | Sweden |
| FG002 | Placebo | Placebo to Epanova + placebo to Fenofibrate |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Epanova | Epanova 4 g/day + placebo to Fenofibrate |
| BG001 | Fenofibrate | Fenofibrate 200 mg/ day + placebo to Epanova |
| BG002 | Placebo | Placebo to Epanova + placebo to Fenofibrate |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Age, Customized | Count of Participants | Participants |
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| Sex/Gender, Customized | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Geometric Mean | 95% Confidence Interval | ratio of % liver fat | Baseline and 12 weeks |
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| 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. | 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. | Posted | Geometric Mean | 95% Confidence Interval | ratio of % liver fat | 12 weeks |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Epanova | Epanova 4 g/day + placebo to Fenofibrate | 1 | 25 | 17 | 25 | ||
| EG001 | Fenofibrate | Fenofibrate 200 mg/ day + placebo to Epanova | 0 | 27 | 15 | 27 | ||
| EG002 | Placebo | Placebo to Epanova + placebo to Fenofibrate | 0 | 26 | 8 | 26 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Urosepsis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Abdominal Distension | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Abdominal tenderness | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Bladder pain | Renal and urinary disorders | MedDRA 19.0 | Systematic Assessment |
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| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Eructation | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Faeces discoloured | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Gallbladder pain | Hepatobiliary disorders | MedDRA 19.0 | Systematic Assessment |
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| Gastritis | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Gastroesophageal reflux disease | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Haematochezia | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA 19.0 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Localised infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Malaise | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Petachiae | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Radius fracture | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Tendon operation | Surgical and medical procedures | MedDRA 19.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Vaginal infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Torbjörn Lundström | AstraZeneca | 46 317064100 | Torbjorn.lundstrom@astrazeneca.com |
| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| D015228 | Hypertriglyceridemia |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C000708078 | omega-3 carboxylic acid |
| D011345 | Fenofibrate |
| ID | Term |
|---|---|
| D058607 | Fibric Acids |
| D058610 | Isobutyrates |
| D002087 | Butyrates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D010647 | Phenyl Ethers |
| D004987 | Ethers |
| D001577 | Benzophenones |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010636 | Phenols |
| D007659 | Ketones |
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| >=50 - <65 |
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| >=65 |
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| Male |
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| Other |
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| White |
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