Efficacy and Safety of Oltipraz for Liver Fat Reduction in Patients With Non-Alcoholic Fatty Liver Disease Except for Liver Cirrhosis

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of Oltipraz for Liver Fat Reduction in Patients With Non-Alcoholic Fatty Liver Disease Except for Liver Cirrhosis

Dithiolethiones, a novel class of adenosine monophosphate-activated protein kinase (AMPK) activators, prevent insulin resistance through AMPK-dependent p70 ribosomal S6 kinase-1 (S6K1) inhibition. And it is well known that the modulation of S6K1 by oltipraz inhibited the development of insulin resistance and hyperglycemia through the AMPK-S6K1 pathway.Also some research reported that LXRg (a member of the nuclear hormone receptor)-mediated increases in SREBP-1c (the sterol regulatory element-binding protein-1c gene) promote the expression of lipogenic genes and enhance fatty acid synthesis and oltipraz inhibits LXRg and SREBP-c. Therefore, Oltipraz inhibits fatty acid synthesis through AMPK-S6K1 pathway and LXRg-SREBP-1c pathway in liver.

Study Overview

• Status: Completed
• Conditions: Non-alcholic Fatty Liver Disease
• Intervention / Treatment: Drug: Placebo; Drug: Oltipraz 1 (90mg); Drug: Oltipraz 2 (120mg)

• Study Type: Interventional
• Enrollment (Actual): 283
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Goyang-si
    • Ilsan-ro Ilsan-donggu, Goyang-si, Korea, Republic of, 410-719
      • NHUS Ilsan Hospital
  • Gyeonggi-do
    • Dahwa-dong, Ilsanseo-gu, Goyang-si, Gyeonggi-do, Korea, Republic of, 411-706
      • Inje University Ilsan Paik Hospital
  • Seoul
    • Daehak-ro Jongno-gu, Seoul, Korea, Republic of, 110-744
      • Seoul National University Hospital
    • Gurodong-ro, Seoul, Korea, Republic of, 152-703
      • Korea University Guro Hospital
    • Sindaebang-dong Dongjak-gu, Seoul, Korea, Republic of, 156-707
      • Boramae Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients over 19 under 75 years of age
• Patients with non-alcoholic fatty liver disease except for cirrhosis
• Patients who have abnormal ALT, AST
• Patients who are satisfied with laboratory test
• Patients who agree to contraception
• Patients who can keet the diet

Exclusion Criteria:

• Over 2 ratio of AST to ALT
• Type 1 diabetes mellitus (insulin-dependent diabetes mellitus) or Type 2 diabetes mellitus(not controlled)
• Disorder in liver function with an exception of non-alcoholic fatty liver
• Patients with malignant tumors
• Patients who have been taken drugs induced fatty liver within 8 weeks of participation in this study
• Patients who has been taken any medications that could affect the treatment for NAFLD within 4 weeks
• Patients who have been taken Vitamin E (≥ 800 IU/day), thiazolidinediones, orlistat within 12 weeks
• Patients who had a Bariatric surgery less than 6 month prior to the participation in the study
• Patients who are judged by investigator that participation of the study is difficult due to disease as follow;
• Any history of immune disorder
• Patients who have received treatment that may affect liver function within 1 month prior to the participation in the study
• Patient who has been administered other investigational product within 1 month prior to the participation in the study
• Patient who is not allowed to get MRS test: pacemaker, shunt and etc
• Pregnant or nursing women
• anti-HIV antibody (+)
• Patient who considered ineligible for participation in the study as Investigator's judgment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo Comparator / Tid (total 0mg)	Drug: Placebo
Experimental: Oltipraz 1; Total 90mg, by mouth, tid	Drug: Oltipraz 1 (90mg)
Experimental: Oltipraz 2; Total 120mg, by mouth, tid	Drug: Oltipraz 2 (120mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRS(magnetic resonance spectroscopy)	To evaluate the efficacy of the Oltipraz on change in quantity of liver fat (% change) assessed by MRS from baseline to 24 weeks in patients.	24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
change in liver fat concentration	24 weeks
change in BMI	8, 16, 24 weeks
change in NAFLD Fibrosis score (NFS)	24 weeks
change in ALT, AST, γ-GT	8, 16, 24 weeks
change in Cholesterol (total, LDL, HDL, VLDL), Triglyceride (TG)	8, 16, 24 weeks
change in HOMA-IR	8, 16, 24 weeks
change in waist circumference	24 weeks

Other Outcome Measures

Outcome Measure	Time Frame
change in Adipokine, CK-18	8, 16, 24 weeks

Collaborators and Investigators

• Sponsor: PharmaKing

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: February 19, 2014
• First Submitted That Met QC Criteria: February 20, 2014
• First Posted (Estimate): February 21, 2014

Study Record Updates

• Last Update Posted (Estimate): March 30, 2016
• Last Update Submitted That Met QC Criteria: March 29, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Fibrosis; Liver Diseases; Fatty Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Protective Agents; Antiparasitic Agents; Anticarcinogenic Agents; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Oltipraz
• Other Study ID Numbers: PMK-N01GI1_Phase 3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No