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

Phase 2

Completed

• Conditions: Steatohepatitis
• Interventions: Drug: Placebo capsule; Drug: EPA-E 300 mg capsule

• Registration Number: NCT01154985
• Lead Sponsor: Mochida Pharmaceutical Company, Ltd.

Brief Summary

This is a controlled study to determine the effectiveness and safety of ethyl icosapentate (EPA-E) in the treatment of adult patients with non-alcoholic steatohepatitis (NASH).

Detailed Description

This is a phase II, double-blinded, placebo-controlled study to investigate the safety, efficacy, and pharmacokinetic profile of two doses of EPA-E in adult subjects with NASH. Subjects are required to have a liver biopsy with proven NASH in the 6 month period prior to screening. Up to 70 subjects will be enrolled into each treatment arm in a 1:1:1 ratio, for a total of 210 subjects. Subjects will be stratified at randomization by presence or absence of diabetes. Duration of treatment is 12 months.

Study Timeline

• Study Start: 2010-06
• Study First Submitted: 2010-06-29
• Study First Submitted QC: 2010-06-30
• Study First Posted: 2010-07-01
• Primary Completion: 2012-10
• Study Completion: 2012-10
• Disposition First Submitted: 2013-10-17
• Disposition First Submitted QC: 2013-10-17
• Disposition First Posted: 2013-11-11
• Status Verified: 2014-10
• Results First Submitted: 2014-10-15
• Results First Submitted QC: 2014-11-13
• Last Update Submitted: 2014-11-13
• Results First Posted: 2014-11-20
• Last Update Posted: 2014-11-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 243

Inclusion Criteria

• Diagnosis of definite NASH
• Patients with diabetes taking stable doses of anti-diabetic agents are eligible
• No significant concomitant medical illness

Exclusion Criteria

• Diagnosis of cirrhosis.

• Serum ALT > 300 U/L

• Use of drugs associated with steatohepatitis

• Use of the following anit-NASH agents:

  1. Vitamin E > 60 IU per day
  2. Omega-3-acid ethyl esters or omega-3-polyunsaturated fatty acid (PUFA)-containing supplements > 200 mg per day
  3. Thiazolidinediones (e.g. pioglitazone)

• Use of non-stable doses of the following anti-NASH agents: HMGCoA reductase inhibitors (statins), fibrates, probucol, ezetimibe, ursodiol (UDCA), taurine, betaine, N-acetylcysteine, s-adenosylmethionine (SAM-E), milk thistle, anti-TNF therapies, or probiotics.

• Other liver disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo capsule	3x placebo capsules TID
EPA-E 1800 mg/day	EPA-E 300 mg capsule	2x EPA-E 300 mg capsules + 1placebo capsule TID
EPA-E 2700 mg/day	EPA-E 300 mg capsule	3x EPA-E 300 mg capsules TID

Primary Outcome Measures

Name	Time	Method
Alanine Transaminase (ALT) Levels	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
Histological Response Defined by Change From Baseline in Standardized Scoring of Liver Biopsies	12 months	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

Trial Locations

Locations (2)

Mochida Investigative Site; 🇵🇷 San Juan, Puerto Rico

Mochida Investigative Site (2 sites); 🇺🇸 Houston, Texas, United States