Efficacy and Safety of Oltipraz in the Patients With Liver Fibrosis and Cirrhosis

A Randomized, Double-Blind, Placebo-Controlled Phase II Multicenter Trial of Oltipraz for the Evaluation of Efficacy and Safety in the Patients With Liver Fibrosis and Cirrhosis Induced by Chronic Hepatitis Type B or C

This study investigated the effectiveness and safety of oltipraz therapy in treating patients with cirrhosis induced by chronic hepatitis type B or C.

Study Overview

• Status: Completed
• Conditions: Liver Cirrhosis; Liver Fibrosis
• Intervention / Treatment: Drug: placebo; Drug: oltipraz

Detailed Description

Oltipraz [5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione] has been extensively studied as a cancer chemopreventive agent. Comprehensive mechanistic and phase IIa studies supported the notion that oltipraz exerts chemopreventive effects, as supported by Phase IIa human clinical studies of oltipraz on cancer chemoprevention, conducted in Qidong, China. Hepatic stellate cells cause synthesis of large quantities of extracellular matrix. Transforming growth factor beta1 (TGF-beta1), as a key fibrogenic mediator for fibrogenesis after injuries through deposition of extracellular matrix and inhibition of collagenase activity in the liver, is associated with the regulation of cell growth and differentiation and causes synthesis of extracellular matrix proteins and cellular receptors for matrix proteins. Previously, we reported the effectiveness of oltipraz in regeneration of cirrhotic liver, which includes reduction of the intensities of liver fibrotic and cirrhotic nodules, elimination of accumulated extracellular matrix, and regeneration of cirrhotic liver in animal models. Oltipraz completely resolves fibrosis in the cirrhotic liver, thereby improving viability. TGF-beta1 signaling plays an important role in liver fibrogenesis and cirrhosis as evidenced by receptor knockout experiments. No therapeutic agent that is active in interrupting TGF-beta1 signaling is available, proposing that C/EBP serve as a molecular target for the treatment of liver cirrhosis.

• Study Type: Interventional
• Enrollment: 81
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Kyungki-Do
    • Sosa-Dong, Wonmi-Gu, Kyungki-Do, Korea, Republic of
      • The Catholic University of Korea Holy Family Hospital
  • Seoul
    • Banpo-Dong, Seocho-Gu, Seoul, Korea, Republic of
      • The Catholic University of Korea Seoul St. Mary'S Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients with fibrosis and cirrhosis induced by chronic hepatitis type B or C
• patients with HbsAg, Anti-HCV or HCV RNA positive

Exclusion Criteria:

• treatment with antiviral agents, immunosuppressants, glucocorticoids, within the 6 months or with biphenyl dimethyl dicarboxylate one month
• treatment with any investigational drug (except CJ11555PK or CJ-OPZ-201PK) within one month
• Child-Pugh class C, Use of a mean daily dose of 80 g alcohol with the one month, of enzyme inducers or inhibitors, or of drug abuse that might affect this study
• a known hypersensitivity to oltipraz or its structurally related compounds
• ascites, hemorrhage from varicoses, uncompensated LC with the history of hepatic encephalopathy within the 6 months
• hepatocellular carcinoma (a rising serum level of α-fetoprotein or a suspicious foci on hepatic ultrasonography at screening or), liver transplantation
• pregnancy or lactation, unwillingness of contraception during the study period
• other serious concurrent illness (e.g., severe hemorrhagic GI, renal, pulmonary, neurological, cardiovascular (CHF of class III or above; a history of MI within the past 6 months) diseases, or cancer, autoimmunity or psychological diseases)
• any patients who is inappropriate or has unwillingness of clinical study as judged by participating clinicians
• bilirubin content greater than 2.0 mg/dL, prothrombin time longer than 4 sec, and serum albumin below 2.5 g/dL

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: placebo	Drug: placebo
EXPERIMENTAL: oltipraz	Drug: oltipraz; 60mg bid 90mg qd

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Ishak fibrosis score	24 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
The Modified Knodell's HAI score	24 weeks
Child-Pugh score	24 weeks

Collaborators and Investigators

• Sponsor: HK inno.N Corporation

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Study Completion: February 1, 2007

Study Registration Dates

• First Submitted: August 10, 2009
• First Submitted That Met QC Criteria: August 10, 2009
• First Posted (ESTIMATE): August 11, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): August 11, 2009
• Last Update Submitted That Met QC Criteria: August 10, 2009
• Last Verified: August 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis; 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: CJ-OPZ-201 study