NCT02068339

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

Completed Phase 3 Last updated 29 March 2016

What this trial tests

Phase 3 trial testing Oltipraz 1 (90mg) in Non-alcholic Fatty Liver Disease in 283 participants. Completed in 1 March 2016.

Timeline

1 February 2014

Primary endpoint
1 February 2016

1 March 2016

Quick facts

Lead sponsor	PharmaKing
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	283
Start date	1 February 2014
Primary completion	1 February 2016
Estimated completion	1 March 2016
Sites	5 locations across South Korea

Drugs / interventions tested

• Oltipraz 1 (90mg) — full drug profile →
• Placebo
• Oltipraz 2 (120mg) — full drug profile →

Conditions studied

• Non-alcholic Fatty Liver Disease — all drugs for Non-alcholic Fatty Liver Disease →

Sponsor

PharmaKing — full company profile →

Who can join

Adults 19 to 75, any sex, with Non-alcholic Fatty Liver Disease. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• MRS(magnetic resonance spectroscopy)
  Time frame: 24 weeks
  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.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Activators and Inhibitors of NRF2: A Review of Their Potential for Clinical Development.
   Robledinos-Antón N, Fernández-Ginés R, Manda G, Cuadrado A. · · 2019 · cited 443× · PMID 31396308 · DOI 10.1155/2019/9372182
2. Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH).
   Xu X, Poulsen KL, Wu L, Liu S, et al · · 2022 · cited 235× · PMID 35963848 · DOI 10.1038/s41392-022-01119-3
3. Therapeutic targets, novel drugs, and delivery systems for diabetes associated NAFLD and liver fibrosis.
   Kumar V, Xin X, Ma J, Tan C, et al · · 2021 · cited 128× · PMID 34314787 · DOI 10.1016/j.addr.2021.113888
4. <i>In vitro</i> models for non-alcoholic fatty liver disease: Emerging platforms and their applications.
   Ramos MJ, Bandiera L, Menolascina F, Fallowfield JA. · · 2022 · cited 94× · PMID 34977507 · DOI 10.1016/j.isci.2021.103549
5. Nrf2 Is an Attractive Therapeutic Target for Retinal Diseases.
   Nakagami Y. · · 2016 · cited 66× · PMID 27818722 · DOI 10.1155/2016/7469326
6. Pathogenesis of Nonalcoholic Steatohepatitis and Hormone-Based Therapeutic Approaches.
   Kim KH, Lee MS. · · 2018 · cited 49× · PMID 30197624 · DOI 10.3389/fendo.2018.00485
7. Druggability of lipid metabolism modulation against renal fibrosis.
   Chen YY, Chen XG, Zhang S. · · 2022 · cited 43× · PMID 33990764 · DOI 10.1038/s41401-021-00660-1
8. Early aging and premature vascular aging in chronic kidney disease.
   Tanriover C, Copur S, Mutlu A, Peltek IB, et al · · 2023 · cited 34× · PMID 37915901 · DOI 10.1093/ckj/sfad076