Trial Outcomes & Findings for Double-Blind, Placebo-Controlled Study of Two Doses of EPA-E in Patients With Non Alcoholic Steatohepatitis (NASH) (NCT NCT01154985)

Last Updated: 2014-11-20

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

243 participants

Primary outcome timeframe

12 months

Results posted on

2014-11-20

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Placebo: Placebo three times a day (TID) for 365 days	EPA-E 1800 mg/Day EPA-E: 600 mg TID for 365 days	EPA-E 2700 mg/Day EPA-E: 900 mg TID for 365 days
Overall Study STARTED	75	82	86
Overall Study Full Analysis Set	75	82	86
Overall Study Valid Biopsy -Baseline and Month 12.5	60	62	68
Overall Study Efficacy Evaluable Analysis Set	55	55	64
Overall Study COMPLETED	58	55	68
Overall Study NOT COMPLETED	17	27	18

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Double-Blind, Placebo-Controlled Study of Two Doses of EPA-E in Patients With Non Alcoholic Steatohepatitis (NASH)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=75 Participants Placebo: Placebo three times a day (TID) for 365 days	EPA-E 1800 mg/Day n=82 Participants EPA-E: 600 mg TID for 365 days	EPA-E 2700 mg/Day n=86 Participants EPA-E: 900 mg TID for 365 days	Total n=243 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	67 Participants n=5 Participants	74 Participants n=7 Participants	80 Participants n=5 Participants	221 Participants n=4 Participants
Age, Categorical >=65 years	8 Participants n=5 Participants	8 Participants n=7 Participants	6 Participants n=5 Participants	22 Participants n=4 Participants
Age, Continuous	50.5 years STANDARD_DEVIATION 12.45 • n=5 Participants	47.8 years STANDARD_DEVIATION 12.48 • n=7 Participants	47.8 years STANDARD_DEVIATION 11.14 • n=5 Participants	48.6 years STANDARD_DEVIATION 12.02 • n=4 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	48 Participants n=7 Participants	57 Participants n=5 Participants	148 Participants n=4 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	34 Participants n=7 Participants	29 Participants n=5 Participants	95 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants	15 Participants n=7 Participants	15 Participants n=5 Participants	45 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	60 Participants n=5 Participants	67 Participants n=7 Participants	71 Participants n=5 Participants	198 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants	10 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Race (NIH/OMB) White	68 Participants n=5 Participants	77 Participants n=7 Participants	75 Participants n=5 Participants	220 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: 12 months

Population: 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

Outcome measures

Outcome measures
Measure	Placebo n=55 Participants Placebo: Placebo three times a day (TID) for 365 days	EPA-E 1800 mg/Day n=55 Participants EPA-E: 600 mg TID for 365 days	EPA-E 2700 mg/Day n=64 Participants EPA-E: 900 mg TID for 365 days
Histological Response Defined by Change From Baseline in Standardized Scoring of Liver Biopsies	18 participants	18 participants	20 participants

PRIMARY outcome

Timeframe: 3 month endpoint

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; 1. EPA-E 2700 mg and Placebo groups 2. EPA-E 1800 mg and Placebo groups

Outcome measures

Outcome measures
Measure	Placebo n=55 Participants Placebo: Placebo three times a day (TID) for 365 days	EPA-E 1800 mg/Day n=55 Participants EPA-E: 600 mg TID for 365 days	EPA-E 2700 mg/Day n=64 Participants EPA-E: 900 mg TID for 365 days
Alanine Transaminase (ALT) Levels	-19.3 U/L Standard Error 4.61	-3.0 U/L Standard Error 4.61	2.8 U/L Standard Error 4.27

PRIMARY outcome

Timeframe: 6 months

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; 1. EPA-E 2700 mg and Placebo groups 2. EPA-E 1800 mg and Placebo groups

Outcome measures

Outcome measures
Measure	Placebo n=55 Participants Placebo: Placebo three times a day (TID) for 365 days	EPA-E 1800 mg/Day n=55 Participants EPA-E: 600 mg TID for 365 days	EPA-E 2700 mg/Day n=64 Participants EPA-E: 900 mg TID for 365 days
Alanine Transaminase (ALT) Levels	-19.1 U/L Standard Deviation 4.79	-9.5 U/L Standard Deviation 4.80	-3.0 U/L Standard Deviation 4.45

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 71 other events

Deaths: 0 deaths

EPA-E 1800 mg/Day

Serious events: 8 serious events

Other events: 65 other events

Deaths: 0 deaths

EPA-E 2700 mg/Day

Serious events: 5 serious events

Other events: 74 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Hironori Sato, Director

Mochida Pharmaceutical Company Ltd.

Phone: +81-3-3225-6331

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Placebo n=75 participants at risk Placebo: Placebo three times a day (TID) for 365 days	EPA-E 1800 mg/Day n=82 participants at risk EPA-E: 600 mg TID for 365 days	EPA-E 2700 mg/Day n=86 participants at risk EPA-E: 900 mg TID for 365 days
Blood and lymphatic system disorders Thrombocytopenia	1.3% 1/75 • 1 year Adverse events solicited at each study visit.	0.00% 0/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
Cardiac disorders Angina pectoris	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	1.2% 1/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
Gastrointestinal disorders Abdominal pain	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	2.4% 2/82 • 1 year Adverse events solicited at each study visit.	1.2% 1/86 • 1 year Adverse events solicited at each study visit.
Gastrointestinal disorders Pancreatitis	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	2.4% 2/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
Gastrointestinal disorders pancreatitis relapsing	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	1.2% 1/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
General disorders Non-cardiac chest pain	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	2.4% 2/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
General disorders Asthenia	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	1.2% 1/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
General disorders Chest pain	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	1.2% 1/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
General disorders Pyrexia	1.3% 1/75 • 1 year Adverse events solicited at each study visit.	0.00% 0/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
Infections and infestations Appendicitis	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	1.2% 1/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
Infections and infestations Pneumonia	1.3% 1/75 • 1 year Adverse events solicited at each study visit.	0.00% 0/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
Infections and infestations Post procedural pneumonia	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	0.00% 0/82 • 1 year Adverse events solicited at each study visit.	1.2% 1/86 • 1 year Adverse events solicited at each study visit.
Injury, poisoning and procedural complications Post procedural bile leak	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	0.00% 0/82 • 1 year Adverse events solicited at each study visit.	1.2% 1/86 • 1 year Adverse events solicited at each study visit.
Injury, poisoning and procedural complications Post procedural hematoma	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	1.2% 1/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
Investigations Electrocardiogram T wave inversion	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	1.2% 1/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
Metabolism and nutrition disorders Dehydration	1.3% 1/75 • 1 year Adverse events solicited at each study visit.	0.00% 0/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	0.00% 0/82 • 1 year Adverse events solicited at each study visit.	1.2% 1/86 • 1 year Adverse events solicited at each study visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Carcinoid tumor	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	1.2% 1/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myelomonocytic leukaemia	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	1.2% 1/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Multiple myeloma	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	1.2% 1/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
Nervous system disorders Transient ischemic attack	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	2.4% 2/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
Nervous system disorders Complicated migraine	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	1.2% 1/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
Nervous system disorders Multiple sclerosis relapse	1.3% 1/75 • 1 year Adverse events solicited at each study visit.	0.00% 0/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
Nervous system disorders Syncope	1.3% 1/75 • 1 year Adverse events solicited at each study visit.	0.00% 0/82 • 1 year Adverse events solicited at each study visit.	1.2% 1/86 • 1 year Adverse events solicited at each study visit.
Psychiatric disorders Panic attack	1.3% 1/75 • 1 year Adverse events solicited at each study visit.	0.00% 0/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	1.2% 1/82 • 1 year Adverse events solicited at each study visit.	1.2% 1/86 • 1 year Adverse events solicited at each study visit.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	1.2% 1/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.

Measure	Placebo n=75 participants at risk Placebo: Placebo three times a day (TID) for 365 days	EPA-E 1800 mg/Day n=82 participants at risk EPA-E: 600 mg TID for 365 days	EPA-E 2700 mg/Day n=86 participants at risk EPA-E: 900 mg TID for 365 days
Blood and lymphatic system disorders Anaemia	5.3% 4/75 • 1 year Adverse events solicited at each study visit.	3.7% 3/82 • 1 year Adverse events solicited at each study visit.	2.3% 2/86 • 1 year Adverse events solicited at each study visit.
Gastrointestinal disorders Nausea	9.3% 7/75 • 1 year Adverse events solicited at each study visit.	9.8% 8/82 • 1 year Adverse events solicited at each study visit.	18.6% 16/86 • 1 year Adverse events solicited at each study visit.
Gastrointestinal disorders Diarrhoea	17.3% 13/75 • 1 year Adverse events solicited at each study visit.	7.3% 6/82 • 1 year Adverse events solicited at each study visit.	12.8% 11/86 • 1 year Adverse events solicited at each study visit.
Gastrointestinal disorders Vomiting	5.3% 4/75 • 1 year Adverse events solicited at each study visit.	3.7% 3/82 • 1 year Adverse events solicited at each study visit.	11.6% 10/86 • 1 year Adverse events solicited at each study visit.
Gastrointestinal disorders Abdominal pain	5.3% 4/75 • 1 year Adverse events solicited at each study visit.	6.1% 5/82 • 1 year Adverse events solicited at each study visit.	2.3% 2/86 • 1 year Adverse events solicited at each study visit.
Gastrointestinal disorders Abdominal pain upper	1.3% 1/75 • 1 year Adverse events solicited at each study visit.	3.7% 3/82 • 1 year Adverse events solicited at each study visit.	7.0% 6/86 • 1 year Adverse events solicited at each study visit.
Gastrointestinal disorders Gastroesphageal reflux disease	5.3% 4/75 • 1 year Adverse events solicited at each study visit.	2.4% 2/82 • 1 year Adverse events solicited at each study visit.	4.7% 4/86 • 1 year Adverse events solicited at each study visit.
General disorders Fatigue	8.0% 6/75 • 1 year Adverse events solicited at each study visit.	3.7% 3/82 • 1 year Adverse events solicited at each study visit.	4.7% 4/86 • 1 year Adverse events solicited at each study visit.
General disorders Oedema peripheral	8.0% 6/75 • 1 year Adverse events solicited at each study visit.	3.7% 3/82 • 1 year Adverse events solicited at each study visit.	4.7% 4/86 • 1 year Adverse events solicited at each study visit.
General disorders Pyrexia	5.3% 4/75 • 1 year Adverse events solicited at each study visit.	2.4% 2/82 • 1 year Adverse events solicited at each study visit.	3.5% 3/86 • 1 year Adverse events solicited at each study visit.
Infections and infestations Urinary tract infection	14.7% 11/75 • 1 year Adverse events solicited at each study visit.	13.4% 11/82 • 1 year Adverse events solicited at each study visit.	9.3% 8/86 • 1 year Adverse events solicited at each study visit.
Infections and infestations Nasopharyngitis	12.0% 9/75 • 1 year Adverse events solicited at each study visit.	3.7% 3/82 • 1 year Adverse events solicited at each study visit.	7.0% 6/86 • 1 year Adverse events solicited at each study visit.
Infections and infestations Sinusitis	6.7% 5/75 • 1 year Adverse events solicited at each study visit.	4.9% 4/82 • 1 year Adverse events solicited at each study visit.	8.1% 7/86 • 1 year Adverse events solicited at each study visit.
Infections and infestations Gastroenteritis viral	4.0% 3/75 • 1 year Adverse events solicited at each study visit.	2.4% 2/82 • 1 year Adverse events solicited at each study visit.	9.3% 8/86 • 1 year Adverse events solicited at each study visit.
Infections and infestations Upper respiratory tract infection	4.0% 3/75 • 1 year Adverse events solicited at each study visit.	6.1% 5/82 • 1 year Adverse events solicited at each study visit.	5.8% 5/86 • 1 year Adverse events solicited at each study visit.
Infections and infestations Bronchitis	6.7% 5/75 • 1 year Adverse events solicited at each study visit.	1.2% 1/82 • 1 year Adverse events solicited at each study visit.	4.7% 4/86 • 1 year Adverse events solicited at each study visit.
Infections and infestations Diverticulitis	5.3% 4/75 • 1 year Adverse events solicited at each study visit.	0.00% 0/82 • 1 year Adverse events solicited at each study visit.	1.2% 1/86 • 1 year Adverse events solicited at each study visit.
Injury, poisoning and procedural complications Procedural pain	5.3% 4/75 • 1 year Adverse events solicited at each study visit.	2.4% 2/82 • 1 year Adverse events solicited at each study visit.	1.2% 1/86 • 1 year Adverse events solicited at each study visit.
Investigations Blood creatine phosphokinase increased	5.3% 4/75 • 1 year Adverse events solicited at each study visit.	2.4% 2/82 • 1 year Adverse events solicited at each study visit.	0.00% 0/86 • 1 year Adverse events solicited at each study visit.
Musculoskeletal and connective tissue disorders Back pain	8.0% 6/75 • 1 year Adverse events solicited at each study visit.	3.7% 3/82 • 1 year Adverse events solicited at each study visit.	5.8% 5/86 • 1 year Adverse events solicited at each study visit.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/75 • 1 year Adverse events solicited at each study visit.	3.7% 3/82 • 1 year Adverse events solicited at each study visit.	5.8% 5/86 • 1 year Adverse events solicited at each study visit.
Nervous system disorders Dizziness	5.3% 4/75 • 1 year Adverse events solicited at each study visit.	4.9% 4/82 • 1 year Adverse events solicited at each study visit.	1.2% 1/86 • 1 year Adverse events solicited at each study visit.
Psychiatric disorders Depression	5.3% 4/75 • 1 year Adverse events solicited at each study visit.	4.9% 4/82 • 1 year Adverse events solicited at each study visit.	4.7% 4/86 • 1 year Adverse events solicited at each study visit.
Vascular disorders Hypertension	6.7% 5/75 • 1 year Adverse events solicited at each study visit.	4.9% 4/82 • 1 year Adverse events solicited at each study visit.	4.7% 4/86 • 1 year Adverse events solicited at each study visit.