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Efficacy and Safety of Oltipraz in the Patients With Non-alcoholic Fatty Liver Disease (PMK-N01GI1)

Primary Purpose

Non-alcoholic Fatty Liver Disease

Status
Completed
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Placebo
Oltipraz
Sponsored by
PharmaKing
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-alcoholic Fatty Liver Disease

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients over 18, under 75 years of age
  • Patients with non-alcoholic fatty liver disease

Exclusion Criteria:

  • Over 2 ratio of AST to ALT
  • Type 1 diabetes mellitus (insulin-dependent diabetes mellitus)
  • Disorder in liver function with an exception of non-alcoholic fatty liver (e.g. Virus infection, biliary atresia, autoimmune hepatitis and etc.)
  • Patients who have been taken drugs induced fatty liver for over 3 month within 1 year of participation in this study; amiodarone, tamoxifen, methotrexate, tetracyclines, glucocorticoids, anabolic steroids, over usual dose of estrogen for hormone replacement therapy and valproate
  • Patients who has been taken any medications that could affect the treatment for non-alcoholic steatohepatitis: insulin, insulin sensitizer(metformin, thiazolidinedione), high dose of vitamin E, high dose of UDCA, pentoxifylline, SAM-e, Betaine, types of Statin, types of fibrate and orlistat
  • 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; hepatic cirrhosis, Wilson's disease, malignant tumor, serious metabolic disease, severe renal disease, severe pulmonary disease, severe cardiovascular disease, severe nervous disease/psychiatric disorder, muscle disease and etc
  • Any history of immune disorder which affect the changes in cytokine:

inflammatory bowel disease, autoimmune thrombocytopenic purpura, system lupus erythematosus, autoimmune hemolytic anemia, severe psoriasis, rheumatic arthritis and etc

  • 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
  • Patient who considered ineligible for participation in the study as Investigator's judgment

Sites / Locations

  • Inje University Ilsan Paik Hospital
  • NHUS Ilsan Hospital
  • Seoul National University Hospital
  • Korea University Guro hospital
  • Boramae Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Oltipraz

Arm Description

Outcomes

Primary Outcome Measures

MRS
To evaluate the efficacy of the Oltipraz on change in quantity of liver fat concentration assessed by MRS from baseline to 24 weeks in patients with non-alcoholic fatty liver disease

Secondary Outcome Measures

change in ALT, AST and total bilirubin
change in Cholesterol, Triglyceride
change in HOMA-IR
change in BMI
changes in NAS
Subjects with liver biopsy:

Full Information

First Posted
June 3, 2011
Last Updated
December 8, 2013
Sponsor
PharmaKing
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1. Study Identification

Unique Protocol Identification Number
NCT01373554
Brief Title
Efficacy and Safety of Oltipraz in the Patients With Non-alcoholic Fatty Liver Disease
Acronym
PMK-N01GI1
Official Title
A Multicenter, Randomized, Double-blind, Placebo-controlled, A Multicenter, Randomized, Double-blind, Placebo-controlled, 3 Parallel Groups, Phase 2 Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Oltipraz in Patients With Non-alcoholic Fatty Liver Disease (Except Liver Cirrhosis)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
May 2011 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
October 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PharmaKing

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-alcoholic Fatty Liver Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
Oltipraz
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
30mig/bid or 60mg/bid P.O
Intervention Type
Drug
Intervention Name(s)
Oltipraz
Intervention Description
30mig/bid or 60mg/bid P.O
Primary Outcome Measure Information:
Title
MRS
Description
To evaluate the efficacy of the Oltipraz on change in quantity of liver fat concentration assessed by MRS from baseline to 24 weeks in patients with non-alcoholic fatty liver disease
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
change in ALT, AST and total bilirubin
Time Frame
24 weeks
Title
change in Cholesterol, Triglyceride
Time Frame
24 weeks
Title
change in HOMA-IR
Time Frame
24 weeks
Title
change in BMI
Time Frame
24 weeks
Title
changes in NAS
Description
Subjects with liver biopsy:
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients over 18, under 75 years of age Patients with non-alcoholic fatty liver disease Exclusion Criteria: Over 2 ratio of AST to ALT Type 1 diabetes mellitus (insulin-dependent diabetes mellitus) Disorder in liver function with an exception of non-alcoholic fatty liver (e.g. Virus infection, biliary atresia, autoimmune hepatitis and etc.) Patients who have been taken drugs induced fatty liver for over 3 month within 1 year of participation in this study; amiodarone, tamoxifen, methotrexate, tetracyclines, glucocorticoids, anabolic steroids, over usual dose of estrogen for hormone replacement therapy and valproate Patients who has been taken any medications that could affect the treatment for non-alcoholic steatohepatitis: insulin, insulin sensitizer(metformin, thiazolidinedione), high dose of vitamin E, high dose of UDCA, pentoxifylline, SAM-e, Betaine, types of Statin, types of fibrate and orlistat 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; hepatic cirrhosis, Wilson's disease, malignant tumor, serious metabolic disease, severe renal disease, severe pulmonary disease, severe cardiovascular disease, severe nervous disease/psychiatric disorder, muscle disease and etc Any history of immune disorder which affect the changes in cytokine: inflammatory bowel disease, autoimmune thrombocytopenic purpura, system lupus erythematosus, autoimmune hemolytic anemia, severe psoriasis, rheumatic arthritis and etc 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 Patient who considered ineligible for participation in the study as Investigator's judgment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
YoonJun Kim, MD.PhD
Organizational Affiliation
Seoul National University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Inje University Ilsan Paik Hospital
City
Dahwa-dong, Ilsanseo-gu
State/Province
Goyang-si, Gyeonggi-do
ZIP/Postal Code
411-706
Country
Korea, Republic of
Facility Name
NHUS Ilsan Hospital
City
Ilsan-ro Ilsan-donggu
State/Province
Goyang-si
ZIP/Postal Code
410-719
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Daehak-ro Jongno-gu
State/Province
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
Facility Name
Korea University Guro hospital
City
Gurodong-ro
State/Province
Seoul
ZIP/Postal Code
152-703
Country
Korea, Republic of
Facility Name
Boramae Hospital
City
Sindaebang-dong Dongjak-gu
State/Province
Seoul
ZIP/Postal Code
156-707
Country
Korea, Republic of

12. IPD Sharing Statement

Citations:
PubMed Identifier
20664537
Citation
Kim SG, Kim YM, Choi YH, Lee MG, Choi JY, Han JY, Cho SH, Jang JW, Um SH, Chon CY, Lee DH, Jang JJ, Yu ES, Lee YS. Pharmacokinetics of oltipraz and its major metabolite (RM) in patients with liver fibrosis or cirrhosis: relationship with suppression of circulating TGF-beta1. Clin Pharmacol Ther. 2010 Sep;88(3):360-8. doi: 10.1038/clpt.2010.89. Epub 2010 Jul 21.
Results Reference
background
PubMed Identifier
28225186
Citation
Kim W, Kim BG, Lee JS, Lee CK, Yeon JE, Chang MS, Kim JH, Kim H, Yi S, Lee J, Cho JY, Kim SG, Lee JH, Kim YJ. Randomised clinical trial: the efficacy and safety of oltipraz, a liver X receptor alpha-inhibitory dithiolethione in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2017 Apr;45(8):1073-1083. doi: 10.1111/apt.13981. Epub 2017 Feb 22.
Results Reference
derived
Links:
URL
http://druginfo.nlm.nih.gov/drugportal/ProxyServlet?mergeData=true&objectHandle=DBMaint&APPLICATION_NAME=drugportal&actionHandle=default&nextPage=jsp/drugportal/ResultScreen.jsp&TXTSUPERLISTID=0064224211&QV1=OLTIPRAZ
Description
Oltipraz

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Efficacy and Safety of Oltipraz in the Patients With Non-alcoholic Fatty Liver Disease

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