Safety And Efficacy Study Of Orally Administered Epeleuto... | NCT02941549

ID	Type	Description	Link
2016-000311-33	EudraCT Number

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	2 x placebo 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks	Other: Placebo capsules
1000 mg Epeleuton	Experimental	1 x Epeleuton 500 mg capsule and 1 x placebo 500 mg capsule orally administered twice a day (4 capsules daily) for 16 weeks	Drug: Epeleuton
2000 mg Epeleuton	Experimental	2 x Epeleuton 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks	Drug: Epeleuton

Name	Type	Description	Arm Group Labels	Other Names
Placebo capsules	Other		Placebo
Epeleuton

Measure	Description	Time Frame
Change in Serum ALT (Alanine Aminotransferase) From Baseline to Week 16	Change in serum ALT from baseline to Week 16 using ANCOVA.	16 Weeks
Change in Liver Stiffness Measurements by Transient Elastography From Baseline to Week 16	To evaluate change in liver stiffness measurements using Transient Elastography from baseline to Week 16 using FibroScan® 502 Touch model or equivalent.	16 Weeks
Number of Treatment Emergent Adverse Events (TEAEs) in Each Treatment Group Leading to Treatment Discontinuation	Subjects with at least 1 TEAE leading to treatment discontinuation	20 Weeks

Measure	Description	Time Frame
Change in Serum ALT (Alanine Aminotransferase) From Baseline to Weeks 2, 4, 8 and 12	Change in serum ALT from baseline to weeks 2, 4, 8 and 12.	12 Weeks
Change in AST (Aspartate Aminotransferase) From Baseline to Weeks 2, 4, 8, 12 and 16

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients diagnosed with NAFLD by the presence of hepatic steatosis on imaging or histology in the absence of any secondary causes.
Patients with an ALT ≥ 1.5 upper limit of normal (ULN) and < 5 ULN on two occasions 7 or more days apart during screening.
Patients with historical liver biopsy showing NASH and/or ≥ F1 fibrosis OR NFS ≥ -1.455 OR Fib- 4 ≥ 1.3 OR Fibroscan ≥8kPa within 3 months of screening.
Patients with a body mass index (BMI) between 25.0 and 40.0 kg/m² inclusive. Patients with a history of controlled obesity or controlled diabetes are allowed on the study.
Patients whose pre-study clinical laboratory findings do not interfere with their participation in the study, in the opinion of the Investigator.
Patients aged between 18 and 75 years inclusive.
Female patients and male patients with female partners of child bearing potential must use adequate contraception or have a sterilized partner for the duration of the study. Adequate contraception is defined as: systemic hormonal contraceptives; intrauterine device or barrier method of contraception in conjunction with spermicide; or agree to sexual abstinence, defined as a patient refraining from heterosexual intercourse during the entire period of risk associated with the study treatments and in line with their preferred and usual lifestyle. Hormonal contraceptives must be on a stable dose for at least one month before baseline.
Patients who are able to communicate well with the Investigator, to understand and comply with the requirements of the study, and understand and sign the written informed consent.

Exclusion Criteria:

Patients with an unstable metabolic condition such as weight change > 5% in the 3 months prior to inclusion.
Patients with medical/surgical history of gastric bypass surgery, orthotopic liver transplant (OLT) or listed for OLT.
Patients with uncontrolled diabetes mellitus type 2, i.e. HbA1c ≥ 9% (75 mmol/mol) at the time of screening.
Patients with decompensated or severe liver disease as evidenced by one or more of the following: confirmed cirrhosis or suspicion of cirrhosis, esophageal varices, ascites, suspicion of portal hypertension, hospitalization for liver disease within 60 days of screening, bilirubin ≥ 2 x ULN, or ALT or AST ≥ 5 x ULN. Patients with Gilbert's syndrome are eligible if the conjugated bilirubin is ≤ 1.5 x ULN.
Patients with inflammatory bowel disease that is either active or requiring medical therapy.
Patients with diagnosed or suspected autoimmune diseases such as systemic lupus erythematosus and/or rheumatoid arthritis.
Patients with a history of or active non-liver malignancies other than curatively treated skin cancer (basal cell or squamous cell carcinomas).
Patients with a significant systemic or major illness other than liver disease, including coronary artery disease, cerebrovascular disease, pulmonary disease, renal insufficiency, serious psychiatric disease, respiratory or hypertensive disease, as well as diabetes and arthritis that, in the opinion of the Investigator, would preclude the patient from participating in and completing the study.
Patients requiring anti-diabetic treatment (including insulin sensitizing agents), and/or lipid lowering treatment, and who are not on a stable dose for at least 3 months prior to screening should be excluded. If patients are insulin dependent this treatment should have commenced at least 3 months prior to screening, however changes in dose are permitted.
Patients with known hypersensitivity to any ingredients of the study treatment.
Patients with a positive test for human immunodeficiency virus antibodies, Hepatitis B surface antigen or Hepatitis C antibodies at screening.
Patients with liver disease of other etiologies such as drug-induced, autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, haemochromatosis, alpha-1 antitrypsin deficiency or Wilson's disease.
Patients with a significant history of drug/solvent abuse, in the opinion of the investigator.
Patients with a history of alcohol abuse in the opinion of the Investigator, or who currently drinks in excess of 21 units per week (males) or 14 units per week (females), whereby a unit consists of 10ml or 8mg of pure alcohol.
Patients who have used dietary supplements rich in omega-3 or omega-6 fatty acids in the 4 weeks prior to baseline.
Patients who have participated in any other clinical study with an investigational drug within 3 months before the first day of administration of study treatment.
Patients who are pregnant, planning pregnancy, breastfeeding and/or are unwilling to use adequate contraception (as specified in inclusion criterion 7) during the study.
Patients, in the opinion of the Investigator, not suitable to participate in the study.

Name	Affiliation	Role
Philip Newsome, MBChB, FRCPE, Ph.D	University of Birmingham	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Georgia Site 1		Kutaisi			Georgia
Georgia Site 2

PubMed Identifier	Type	Citation	Retractions
32779505	Derived	Climax J, Newsome PN, Hamza M, Weissbach M, Coughlan D, Sattar N, McGuire DK, Bhatt DL. Effects of Epeleuton, a Novel Synthetic Second-Generation n-3 Fatty Acid, on Non-Alcoholic Fatty Liver Disease, Triglycerides, Glycemic Control, and Cardiometabolic and Inflammatory Markers. J Am Heart Assoc. 2020 Aug 18;9(16):e016334. doi: 10.1161/JAHA.119.016334. Epub 2020 Aug 11.

ID	Title	Description
FG000	Placebo	2 x placebo 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks
FG001	1000 mg Epeleuton	1 x Epeleuton 500 mg capsule and 1 x placebo 500 mg capsule orally administered twice a day (4 capsules daily) for 16 weeks

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 24, 2018	Dec 16, 2021

ID	Title	Description
BG000	Placebo	2 x placebo 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks
BG001	1000 mg Epeleuton	1 x Epeleuton 500 mg capsule and 1 x placebo 500 mg capsule orally administered twice a day (4 capsules daily) for 16 weeks
BG002	2000 mg Epeleuton	2 x Epeleuton 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00031 BG00132 BG00233 BG00396

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

Change in Serum ALT (Alanine Aminotransferase) From Baseline to Week 16

Change in serum ALT from baseline to Week 16 using ANCOVA.

The Full Analysis Set (FAS) includes all randomised patients who received at least one administration of study treatment and have at least one post-baseline measurement.

Posted

Least Squares Mean

95% Confidence Interval

U/L

16 Weeks

ID	Title	Description
OG000	Placebo	2 x placebo 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks.
OG001	1000 mg Epeleuton	1 x Epeleuton 500 mg capsule and 1 x placebo 500 mg capsule orally administered twice a day (4 capsules daily) for 16 weeks.
OG002	2000 mg Epeleuton	2 x Epeleuton 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks.

Units	Counts
Participants	OG00030 OG00132 OG00231

Title

Denominators

Categories

Title	Measurements
	OG000-16.3(-44.2 to 11.7) OG001-6.9(-34.5 to 20.7) OG002-10.1(-36.9 to 16.8)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		0.5946		LS Mean Difference	-6.9			2-Sided	95	-34.5	20.7					Superiority
OG000 OG002		ANCOVA		0.7309

Primary

Change in Liver Stiffness Measurements by Transient Elastography From Baseline to Week 16

To evaluate change in liver stiffness measurements using Transient Elastography from baseline to Week 16 using FibroScan® 502 Touch model or equivalent.

The Full Analysis Set (FAS) includes all randomised patients who received at least one administration of study treatment and have at least one post-baseline measurement.

Posted

Least Squares Mean

95% Confidence Interval

kPa

16 Weeks

ID	Title	Description
OG000	Placebo	2 x placebo 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks.
OG001	1000 mg Epeleuton	1 x Epeleuton 500 mg capsule and 1 x placebo 500 mg capsule orally administered twice a day (4 capsules daily) for 16 weeks.
OG002	2000 mg Epeleuton	2 x Epeleuton 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks

Units	Counts

Primary

Number of Treatment Emergent Adverse Events (TEAEs) in Each Treatment Group Leading to Treatment Discontinuation

Subjects with at least 1 TEAE leading to treatment discontinuation

The Safety Analysis Set consists of all patients who took at least one administration of study treatment. Patients were analysed according to the treatment actually taken.

Posted

Number

TEAEs

20 Weeks

ID	Title	Description
OG000	Placebo	2 x placebo 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks
OG001	1000 mg Epeleuton	1 x Epeleuton 500 mg capsule and 1 x placebo 500 mg capsule orally administered twice a day (4 capsules daily) for 16 weeks
OG002	2000 mg Epeleuton	2 x Epeleuton 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks

Units	Counts
Participants

Secondary

Change in Serum ALT (Alanine Aminotransferase) From Baseline to Weeks 2, 4, 8 and 12

Change in serum ALT from baseline to weeks 2, 4, 8 and 12.

The Full Analysis Set (FAS) includes all randomised patients who received at least one administration of study treatment and have at least one post-baseline measurement.

Posted

Least Squares Mean

95% Confidence Interval

U/L

12 Weeks

ID	Title	Description
OG000	Placebo	2 x placebo 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks
OG001	1000 mg Epeleuton	1 x Epeleuton 500 mg capsule and 1 x placebo 500 mg capsule orally administered twice a day (4 capsules daily) for 16 weeks
OG002	2000 mg Epeleuton	2 x Epeleuton 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks

Units	Counts
Participants

Secondary

Change in AST (Aspartate Aminotransferase) From Baseline to Weeks 2, 4, 8, 12 and 16

Change in serum AST from baseline to weeks 2, 4, 8, 12 and 16.

The Full Analysis Set (FAS) includes all randomised patients who received at least one administration of study treatment and have at least one post-baseline measurement.

Posted

Least Squares Mean

95% Confidence Interval

U/L

16 Weeks

ID	Title	Description
OG000	Placebo	2 x placebo 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks
OG001	1000 mg Epeleuton	1 x Epeleuton 500 mg capsule and 1 x placebo 500 mg capsule orally administered twice a day (4 capsules daily) for 16 weeks
OG002	2000 mg Epeleuton	2 x Epeleuton 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks

Units	Counts
Participants

Secondary

Change in AST:ALT Ratio From Baseline to Weeks 2, 4, 8, 12 and 16

Change in AST: ALT ratio from baseline to weeks 2, 4, 8, 12 and 16.

The Full Analysis Set (FAS) includes all randomised patients who received at least one administration of study treatment and have at least one post-baseline measurement.

Posted

Least Squares Mean

95% Confidence Interval

Ratio

16 Weeks

ID	Title	Description
OG000	Placebo	2 x placebo 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks
OG001	1000 mg Epeleuton	1 x Epeleuton 500 mg capsule and 1 x placebo 500 mg capsule orally administered twice a day (4 capsules daily) for 16 weeks
OG002	2000 mg Epeleuton	2 x Epeleuton 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks

Units	Counts
Participants

Secondary

Change in FIB-4 Index From Baseline to Week 16

Change in FIB-4 Index from baseline to week 16. This index is based on age, platelet count, ALT level, and AST level and will be assessed at Baseline (Visit 2) and week 16 (Visit 10). FIB-4 was calculated using the following formula: FIB4 = (Age (years) x AST (U/L))/(Platelet count (10^9/L) x √ALT (U/L)). A decrease in FIB-4 represents a positive outcome. A FIB-4 Index of <1.45 indicates none to moderate fibrosis and an Index of >3.25 indicates advanced fibrosis.

The Full Analysis Set (FAS) includes all randomised patients who received at least one administration of study treatment and have at least one post-baseline measurement for FIB-4 Index.

Posted

Least Squares Mean

95% Confidence Interval

Scores on a scale

16 Weeks

ID	Title	Description
OG000	Placebo	2 x placebo 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks
OG001	1000 mg Epeleuton	1 x Epeleuton 500 mg capsule and 1 x placebo 500 mg capsule orally administered twice a day (4 capsules daily) for 16 weeks
OG002	2000 mg Epeleuton	2 x Epeleuton 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks

Secondary

Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Fibrosis Score (NFS) From Baseline to Week 16

Change in NAFLD fibrosis score (NFS) from baseline to week 16. The NFS is based on age, hyperglycemia, BMI, platelet count, albumin level, and AST/ALT ratio. NFS was calculated using the following formula: NAFLD fibrosis score = -1.675 + 0.037 × age (years) + 0.094 × BMI (kg/m^2) + 1.13 × IFG/diabetes (yes = 1, no = 0) + 0.99 × AST/ALT ratio - 0.013 × platelet (×10^9/l) - 0.66 × albumin (g/dl). A decrease in NFS score represents a positive outcome. An NFS score of <-1.455 indicates no advanced fibrosis and a score of >0.676 indicates liver fibrosis.

The Full Analysis Set (FAS) includes all randomised patients who received at least one administration of study treatment and have at least one post-baseline measurement for NFS.

Posted

Least Squares Mean

95% Confidence Interval

Scores on a scale

16 Weeks

ID	Title	Description
OG000	Placebo	2 x placebo 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks
OG001	1000 mg Epeleuton	1 x Epeleuton 500 mg capsule and 1 x placebo 500 mg capsule orally administered twice a day (4 capsules daily) for 16 weeks
OG002	2000 mg Epeleuton

Secondary

Change in ELF (Enhanced Liver Fibrosis Score) From Baseline to Week 16

Change in ELF from baseline to week 16. Enhanced Liver Fibrosis score is an extracellular matrix marker set consisting of tissue inhibitor of metalloproteinases 1 (TIMP-1), amino-terminal propeptide of type III procollagen (PIIINP) and hyaluronic acid (HA). A decrease in ELF score represents a positive outcome. The ELF score was calculated for the instrument based on the following equation: ELF score = 2.494 + 0.846 In (CHA) + 0.735 In (CPIIINP) + 0.391 In (CTIMP-1). An ELF score of less than 7.7 indicates no fibrosis. An ELF score greater than or equal to 9.8 indicates severe fibrosis. An ELF score of 11.3 or greater indicates cirrhosis.

The Full Analysis Set (FAS) includes all randomised patients who received at least one administration of study treatment and have at least one post-baseline measurement for ELF.

Posted

Least Squares Mean

95% Confidence Interval

Scores on a scale

16 Weeks

ID	Title	Description
OG000	Placebo	2 x placebo 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks
OG001	1000 mg Epeleuton	1 x Epeleuton 500 mg capsule and 1 x placebo 500 mg capsule orally administered twice a day (4 capsules daily) for 16 weeks
OG002	2000 mg Epeleuton

Secondary

Change in HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) From Baseline to Weeks 2, 4, 8, 12 and 16

Change in HOMA-IR from baseline to weeks 2,4,8,12,16. Homeostatic model assessment for insulin resistance (HOMA-IR) was assessed as a measure of insulin resistance. HOMA-IR is calculated by multiplying fasting plasma insulin by fasting plasma glucose, then dividing by the constant 405. A decrease in HOMA-IR indicates a positive outcome. HOMA-IR values of greater than 1.9 indicates early insulin resistance and levels above 2.9 indicate significant insulin resistance.

The Full Analysis Set (FAS) includes all randomised patients who received at least one administration of study treatment and have at least one post-baseline measurement.

Posted

Least Squares Mean

95% Confidence Interval

HOMA-IR

16 Weeks

ID	Title	Description
OG000	Placebo	2 x placebo 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks
OG001	1000 mg Epeleuton	1 x Epeleuton 500 mg capsule and 1 x placebo 500 mg capsule orally administered twice a day (4 capsules daily) for 16 weeks
OG002	2000 mg Epeleuton	2 x Epeleuton 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks

Secondary

Change in Adipo-IR (Adipose Tissue Insulin Resistance) From Baseline to Weeks 2, 4, 8, 12 and 16.

Change in Adipo-IR from baseline to weeks 2, 4, 8, 12 and 16. Adipose tissue insulin resistance (Adipo-IR) was assessed as a measure of insulin resistance. Adipo- IR is calculated by multiplying fasting non-esterified fatty acids by fasting insulin. A decrease in Adipo-IR indicates a positive outcome.

The Full Analysis Set (FAS) includes all randomised patients who received at least one administration of study treatment and have at least one post-baseline measurement.

Posted

Least Squares Mean

95% Confidence Interval

Adipo-IR

16 Weeks

ID	Title	Description
OG000	Placebo	2 x placebo 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks
OG001	1000 mg Epeleuton	1 x Epeleuton 500 mg capsule and 1 x placebo 500 mg capsule orally administered twice a day (4 capsules daily) for 16 weeks
OG002	2000 mg Epeleuton	2 x Epeleuton 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks

Secondary

Change in Hepatic Fat Measured by CAP (Controlled Attenuation Parameter) From Baseline to Week 16.

Change in hepatic fat measured by CAP (controlled attenuation parameter) from baseline to week 16 using FibroScan® 502 Touch model or equivalent. CAP score is measured in decibels per meter (dB/m). A reduction in hepatic fat measured non-invasively by CAP indicates an improvement in hepatic steatosis. CAP scores range from 100 to 400dB/m. 0 to 237 dB/M indicates no hepatic steatosis, 238 to 260 dB/m indicates mild hepatic steatosis, 260 to 290 dB/m indicates moderate steatosis and a CAP score greater than 290 dB/m indicates severe steatosis.

The Full Analysis Set (FAS) includes all randomised patients who received at least one administration of study treatment and have at least one post-baseline measurement for hepatic fat measured by CAP.

Posted

Least Squares Mean

95% Confidence Interval

dB/m

16 Weeks

ID	Title	Description
OG000	Placebo	2 x placebo 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks
OG001	1000 mg Epeleuton	1 x Epeleuton 500 mg capsule and 1 x placebo 500 mg capsule orally administered twice a day (4 capsules daily) for 16 weeks
OG002	2000 mg Epeleuton

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Diarrhea	Gastrointestinal disorders	Systematic Assessment	EG0003 affected31 at risk EG0013 affected32 at risk EG0022 affected33 at risk
Dyspepsia	Gastrointestinal disorders	Systematic Assessment	EG0001 affected31 at risk EG0011 affected32 at risk EG0022 affected33 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0002 affected31 at risk EG0012 affected32 at risk EG0020 affected33 at risk
Abdominal Discomfort	Gastrointestinal disorders	Systematic Assessment	EG0001 affected31 at risk EG0011 affected32 at risk EG0021 affected33 at risk
Abdominal pain upper	Gastrointestinal disorders	Systematic Assessment	EG0000 affected31 at risk EG0012 affected32 at risk EG0021 affected33 at risk
Flatulence	Gastrointestinal disorders	Systematic Assessment	EG0001 affected31 at risk EG0011 affected32 at risk EG0021 affected33 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0002 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Abdominal distension	Gastrointestinal disorders	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0021 affected33 at risk
Abdominal pain	Gastrointestinal disorders	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Eructation	Gastrointestinal disorders	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Gastrointestinal sounds abnormal	Gastrointestinal disorders	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Headache	Nervous system disorders	Systematic Assessment	EG0001 affected31 at risk EG0015 affected32 at risk EG0022 affected33 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG0000 affected31 at risk EG0013 affected32 at risk EG0020 affected33 at risk
Dysgeusia	Nervous system disorders	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0023 affected33 at risk
Migraine	Nervous system disorders	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0021 affected33 at risk
Paraesthesia	Nervous system disorders	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0021 affected33 at risk
Somnolence	Nervous system disorders	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Upper respiratory tract infection	Infections and infestations	Systematic Assessment	EG0001 affected31 at risk EG0012 affected32 at risk EG0022 affected33 at risk
Nasopharyngitis	Infections and infestations	Systematic Assessment	EG0001 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Asymptomatic bacteriuria	Infections and infestations	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0021 affected33 at risk
Bronchitis	Infections and infestations	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Furuncle	Infections and infestations	Systematic Assessment	EG0001 affected31 at risk EG0010 affected32 at risk EG0020 affected33 at risk
Gingivitis	Infections and infestations	Systematic Assessment	EG0001 affected31 at risk EG0010 affected32 at risk EG0020 affected33 at risk
Influenza	Infections and infestations	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Localised infection	Infections and infestations	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0021 affected33 at risk
Pneumonia	Infections and infestations	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Subcutaneous abscess	Infections and infestations	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Tracheitis	Infections and infestations	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Viral infection	Infections and infestations	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Viral upper respiratory tract infection	Infections and infestations	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Blood creatine phosphokinase increased	Investigations	Systematic Assessment	EG0003 affected31 at risk EG0013 affected32 at risk EG0020 affected33 at risk
Blood potassium increased	Investigations	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0021 affected33 at risk
Alanine aminotransferase increased	Investigations	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0021 affected33 at risk
Aspartate aminotransferase increased	Investigations	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0021 affected33 at risk
Blood folate decreased	Investigations	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Blood pressure increased	Investigations	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Faecal volume increased	Investigations	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0021 affected33 at risk
Hepatic enzyme increased	Investigations	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Platelet count decreased	Investigations	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0021 affected33 at risk
White blood cell count decreased	Investigations	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Asthenia	General disorders	Systematic Assessment	EG0001 affected31 at risk EG0011 affected32 at risk EG0021 affected33 at risk
Fatigue	General disorders	Systematic Assessment	EG0001 affected31 at risk EG0013 affected32 at risk EG0020 affected33 at risk
Hyperthermia	General disorders	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Pyrexia	General disorders	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 affected31 at risk EG0011 affected32 at risk EG0021 affected33 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0022 affected33 at risk
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0021 affected33 at risk
Myalgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 affected31 at risk EG0010 affected32 at risk EG0020 affected33 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0021 affected33 at risk
Dry skin	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0021 affected33 at risk
Rash	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0021 affected33 at risk
Hair growth abnormal	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 affected31 at risk EG0010 affected32 at risk EG0020 affected33 at risk
Hair texture abnormal	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 affected31 at risk EG0010 affected32 at risk EG0020 affected33 at risk
Night sweats	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Pruritus	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0021 affected33 at risk
Urticaria	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Fall	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Limb injury	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 affected31 at risk EG0010 affected32 at risk EG0020 affected33 at risk
Muscle strain	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Soft tissue injury	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0021 affected33 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected31 at risk EG0012 affected32 at risk EG0020 affected33 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Eye pruritus	Eye disorders	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0021 affected33 at risk
Photopsia	Eye disorders	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Depressed mood	Psychiatric disorders	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Crystalluria	Renal and urinary disorders	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0021 affected33 at risk
Leukocyturia	Renal and urinary disorders	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0021 affected33 at risk
Renal pain	Renal and urinary disorders	Systematic Assessment	EG0001 affected31 at risk EG0010 affected32 at risk EG0020 affected33 at risk
Endodontic procedure	Surgical and medical procedures	Systematic Assessment	EG0000 affected31 at risk EG0010 affected32 at risk EG0021 affected33 at risk
Physiotherapy	Surgical and medical procedures	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Tachycardia	Cardiac disorders	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Vertigo	Ear and labyrinth disorders	Systematic Assessment	EG0000 affected31 at risk EG0011 affected32 at risk EG0020 affected33 at risk
Hyperbilirubinemia	Hepatobiliary disorders	Systematic Assessment	EG0001 affected31 at risk EG0010 affected32 at risk EG0020 affected33 at risk
Vulvovaginal pruritus	Reproductive system and breast disorders	Systematic Assessment	EG0001 affected31 at risk EG0010 affected32 at risk EG0020 affected33 at risk
Lower Respiratory Tract Infection	Infections and infestations	Systematic Assessment	EG0001 affected31 at risk EG0010 affected32 at risk EG0020 affected33 at risk

ID	Term
D005234	Fatty Liver
D008107	Liver Diseases
D004066	Digestive System Diseases

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	2 x placebo 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks	31	1	31	16	31
EG001	1000 mg Epeleuton	1 x Epeleuton 500 mg capsule and 1 x placebo 500 mg capsule orally administered twice a day (4 capsules daily) for 16 weeks	32	0	32	20	32
EG002	2000 mg Epeleuton	2 x Epeleuton 500 mg capsules orally administered twice a day (4 capsules daily) for 16 weeks	33	1	33	14	33

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Pilonidal Cyst	Infections and infestations		Systematic Assessment		EG0001 affected31 at risk EG0010 affected32 at risk EG0020 affected33 at risk
Schizophrenia	Psychiatric disorders		Systematic Assessment		EG0000 affected31 at risk EG0010 affected32 at risk EG0021 affected33 at risk