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

PharmaKing

Status and phase: Completed; Phase 3

Conditions: Non-alcholic Fatty Liver Disease

Treatments: Drug: Oltipraz 1 (90mg); Drug: Oltipraz 2 (120mg); Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02068339

PMK-N01GI1_Phase 3

Details and patient eligibility

About

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.

Enrollment: 283 patients

Sex: All

Ages: 19 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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283 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Placebo Comparator / Tid (total 0mg)

Treatment:

Drug: Placebo

Oltipraz 1

Experimental group

Description:

Total 90mg, by mouth, tid

Treatment:

Drug: Oltipraz 1 (90mg)

Oltipraz 2

Experimental group

Description:

Total 120mg, by mouth, tid

Treatment:

Drug: Oltipraz 2 (120mg)