Double-Blind, Placebo-Controlled Study of Two Doses of EP... | NCT01154985

Status Module

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	3x placebo capsules TID	Drug: Placebo capsule
EPA-E 1800 mg/day	Experimental	2x EPA-E 300 mg capsules + 1placebo capsule TID	Drug: EPA-E 300 mg capsule
EPA-E 2700 mg/day	Experimental	3x EPA-E 300 mg capsules TID	Drug: EPA-E 300 mg capsule

Name	Type	Description	Arm Group Labels	Other Names
Placebo capsule	Drug	3x Placebo capsules three times a day (TID) for 365 days	Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Histological Response Defined by Change From Baseline in Standardized Scoring of Liver Biopsies	Patient is considered a responder if histological examination shows: Composite NAS of <=3 AND no worsening in Fibrosis OR Improvement in NAS by >=2 across at least 2 of the NAS components AND no worsening in fibrosis A priori threshold for statistical significance is p<0.05, 1-sided	12 months
Alanine Transaminase (ALT) Levels	Mean change from baseline at month 3 analyzed by Analysis of Covariance (ANCOVA) in the efficacy evaluable analysis set with treatment group as a factor and baseline ALT as a covariate. Principal comparisons were the response between; EPA-E 2700 mg and Placebo groups EPA-E 1800 mg and Placebo groups	3 month endpoint
Alanine Transaminase (ALT) Levels	Mean change from baseline at month 6 analyzed by Analysis of Covariance (ANCOVA) in the efficacy analysis set with treatment group as a factor and baseline ALT as a covariate. Principal comparisons were the response between; EPA-E 2700 mg and Placebo groups EPA-E 1800 mg and Placebo groups	6 months

Eligibility Module

Facility	Status	City	State	ZIP	Country	Contacts
Mochida Investigative Site		Dothan	Alabama	36305	United States
Mochida Investigative Site

PubMed Identifier	Type	Citation	Retractions
24818764	Derived	Sanyal AJ, Abdelmalek MF, Suzuki A, Cummings OW, Chojkier M; EPE-A Study Group. No significant effects of ethyl-eicosapentanoic acid on histologic features of nonalcoholic steatohepatitis in a phase 2 trial. Gastroenterology. 2014 Aug;147(2):377-84.e1. doi: 10.1053/j.gastro.2014.04.046. Epub 2014 May 9.

Results Section

Participant Flow Module

ID	Title	Description
FG000	Placebo	Placebo: Placebo three times a day (TID) for 365 days
FG001	EPA-E 1800 mg/Day	EPA-E: 600 mg TID for 365 days

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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

Histological Response Defined by Change From Baseline in Standardized Scoring of Liver Biopsies

Patient is considered a responder if histological examination shows:

Composite NAS of <=3 AND no worsening in Fibrosis OR Improvement in NAS by >=2 across at least 2 of the NAS components AND no worsening in fibrosis

A priori threshold for statistical significance is p<0.05, 1-sided

Efficacy Evaluable Analysis Set - All patients in Full Analysis Set who have valid 12-month histological data without major protocol violations, including withdrawn patients with valid 12.5 month histological data after more than 6 months treatment

Posted

Number

participants

12 months

ID	Title	Description
OG000	Placebo	Placebo: Placebo three times a day (TID) for 365 days
OG001	EPA-E 1800 mg/Day	EPA-E: 600 mg TID for 365 days
OG002	EPA-E 2700 mg/Day	EPA-E: 900 mg TID for 365 days

Units	Counts
Participants	OG00055 OG00155 OG00264

Title

Denominators

Categories

Title	Measurements
	OG00018 OG00118 OG00220

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 OG002	Proportion of responders in the EPA-E 1800 mg and 2700 mg groups compared to the proportion of responders in the placebo group compared using the Cochran-Armitage trend test in the Efficacy Evaluable analysis set. P-value less than 5% 1-sided. A total sample size of 210 (70 per arm) was planned to give 80% power for detecting a positive dose-response slope among the 3 treatment arms at 12 months.	Cochran-Armitage trend test		0.57						2-Sided							No	Superiority or Other

Primary

Alanine Transaminase (ALT) Levels

Mean change from baseline at month 3 analyzed by Analysis of Covariance (ANCOVA) in the efficacy evaluable analysis set with treatment group as a factor and baseline ALT as a covariate. Principal comparisons were the response between;

EPA-E 2700 mg and Placebo groups
EPA-E 1800 mg and Placebo groups

Posted

Least Squares Mean

Standard Error

U/L

3 month endpoint

ID	Title	Description
OG000	Placebo	Placebo: Placebo three times a day (TID) for 365 days
OG001	EPA-E 1800 mg/Day	EPA-E: 600 mg TID for 365 days
OG002	EPA-E 2700 mg/Day	EPA-E: 900 mg TID for 365 days

Units	Counts

Primary

Alanine Transaminase (ALT) Levels

Mean change from baseline at month 6 analyzed by Analysis of Covariance (ANCOVA) in the efficacy analysis set with treatment group as a factor and baseline ALT as a covariate. Principal comparisons were the response between;

EPA-E 2700 mg and Placebo groups
EPA-E 1800 mg and Placebo groups

Posted

Mean

Standard Deviation

U/L

6 months

ID	Title	Description
OG000	Placebo	Placebo: Placebo three times a day (TID) for 365 days
OG001	EPA-E 1800 mg/Day	EPA-E: 600 mg TID for 365 days
OG002	EPA-E 2700 mg/Day	EPA-E: 900 mg TID for 365 days

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected75 at risk EG0010 affected82 at risk EG0020 affected86 at risk
Angina pectoris	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected82 at risk EG0020 affected86 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0012 affected82 at risk EG0021 affected86 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0012 affected82 at risk EG0020 affected86 at risk
pancreatitis relapsing	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected82 at risk EG0020 affected86 at risk
Non-cardiac chest pain	General disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0012 affected82 at risk EG0020 affected86 at risk
Asthenia	General disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected82 at risk EG0020 affected86 at risk
Chest pain	General disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected82 at risk EG0020 affected86 at risk
Pyrexia	General disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected75 at risk EG0010 affected82 at risk EG0020 affected86 at risk
Appendicitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected82 at risk EG0020 affected86 at risk
Pneumonia	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 affected75 at risk EG0010 affected82 at risk EG0020 affected86 at risk
Post procedural pneumonia	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0010 affected82 at risk EG0021 affected86 at risk
Post procedural bile leak	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0010 affected82 at risk EG0021 affected86 at risk
Post procedural hematoma	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected82 at risk EG0020 affected86 at risk
Electrocardiogram T wave inversion	Investigations	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected82 at risk EG0020 affected86 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected75 at risk EG0010 affected82 at risk EG0020 affected86 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0010 affected82 at risk EG0021 affected86 at risk
Carcinoid tumor	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected82 at risk EG0020 affected86 at risk
Chronic myelomonocytic leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected82 at risk EG0020 affected86 at risk
Multiple myeloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected82 at risk EG0020 affected86 at risk
Transient ischemic attack	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0012 affected82 at risk EG0020 affected86 at risk
Complicated migraine	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected82 at risk EG0020 affected86 at risk
Multiple sclerosis relapse	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected75 at risk EG0010 affected82 at risk EG0020 affected86 at risk
Syncope	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected75 at risk EG0010 affected82 at risk EG0021 affected86 at risk
Panic attack	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected75 at risk EG0010 affected82 at risk EG0020 affected86 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected82 at risk EG0021 affected86 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0011 affected82 at risk EG0020 affected86 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected75 at risk EG0013 affected82 at risk EG0022 affected86 at risk
Nausea	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0007 affected75 at risk EG0018 affected82 at risk EG00216 affected86 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG00013 affected75 at risk EG0016 affected82 at risk EG00211 affected86 at risk
Vomiting	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected75 at risk EG0013 affected82 at risk EG00210 affected86 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected75 at risk EG0015 affected82 at risk EG0022 affected86 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 affected75 at risk EG0013 affected82 at risk EG0026 affected86 at risk
Gastroesphageal reflux disease	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected75 at risk EG0012 affected82 at risk EG0024 affected86 at risk
Fatigue	General disorders	MedDRA 13.1	Systematic Assessment	EG0006 affected75 at risk EG0013 affected82 at risk EG0024 affected86 at risk
Oedema peripheral	General disorders	MedDRA 13.1	Systematic Assessment	EG0006 affected75 at risk EG0013 affected82 at risk EG0024 affected86 at risk
Pyrexia	General disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected75 at risk EG0012 affected82 at risk EG0023 affected86 at risk
Urinary tract infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG00011 affected75 at risk EG00111 affected82 at risk EG0028 affected86 at risk
Nasopharyngitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0009 affected75 at risk EG0013 affected82 at risk EG0026 affected86 at risk
Sinusitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0005 affected75 at risk EG0014 affected82 at risk EG0027 affected86 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0003 affected75 at risk EG0012 affected82 at risk EG0028 affected86 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0003 affected75 at risk EG0015 affected82 at risk EG0025 affected86 at risk
Bronchitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0005 affected75 at risk EG0011 affected82 at risk EG0024 affected86 at risk
Diverticulitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0004 affected75 at risk EG0010 affected82 at risk EG0021 affected86 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0004 affected75 at risk EG0012 affected82 at risk EG0021 affected86 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 13.1	Systematic Assessment	EG0004 affected75 at risk EG0012 affected82 at risk EG0020 affected86 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0006 affected75 at risk EG0013 affected82 at risk EG0025 affected86 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 affected75 at risk EG0013 affected82 at risk EG0025 affected86 at risk
Dizziness	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected75 at risk EG0014 affected82 at risk EG0021 affected86 at risk
Depression	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0004 affected75 at risk EG0014 affected82 at risk EG0024 affected86 at risk
Hypertension	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0005 affected75 at risk EG0014 affected82 at risk EG0024 affected86 at risk

ID	Term
D005234	Fatty Liver
D065626	Non-alcoholic Fatty Liver Disease

ID	Term
D008107	Liver Diseases
D004066	Digestive System Diseases

ID	Title	Description
BG000	Placebo	Placebo: Placebo three times a day (TID) for 365 days
BG001	EPA-E 1800 mg/Day	EPA-E: 600 mg TID for 365 days
BG002	EPA-E 2700 mg/Day	EPA-E: 900 mg TID for 365 days
BG003	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Placebo: Placebo three times a day (TID) for 365 days	4	75	71	75
EG001	EPA-E 1800 mg/Day	EPA-E: 600 mg TID for 365 days	8	82	65	82
EG002	EPA-E 2700 mg/Day	EPA-E: 900 mg TID for 365 days	5	86	74	86