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

This study has been completed.
Sponsor:
Information provided by:
CJ HealthCare Corporation
ClinicalTrials.gov Identifier:
NCT00956098
First received: August 10, 2009
Last updated: NA
Last verified: August 2009
History: No changes posted
  Purpose

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


Condition Intervention Phase
Liver Fibrosis
Liver Cirrhosis
Drug: oltipraz
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by CJ HealthCare Corporation:

Primary Outcome Measures:
  • Ishak fibrosis score [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The Modified Knodell's HAI score [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Child-Pugh score [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 81
Study Start Date: February 2006
Estimated Study Completion Date: February 2007
Arms Assigned Interventions
Placebo Comparator: placebo Drug: placebo
Experimental: oltipraz Drug: oltipraz
60mg bid 90mg qd

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.

  Eligibility

Ages Eligible for Study:   25 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00956098

Locations
Korea, Republic of
The Catholic University of Korea Holy Family Hospital
Sosa-Dong, Wonmi-Gu, Kyungki-Do, Korea, Republic of
The Catholic University of Korea Seoul St. Mary's Hospital
Banpo-Dong, Seocho-Gu, Seoul, Korea, Republic of
Sponsors and Collaborators
CJ HealthCare Corporation
  More Information

No publications provided

Responsible Party: CJ Cheiljedang Corporation
ClinicalTrials.gov Identifier: NCT00956098     History of Changes
Other Study ID Numbers: CJ-OPZ-201 study
Study First Received: August 10, 2009
Last Updated: August 10, 2009
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Additional relevant MeSH terms:
Fibrosis
Liver Cirrhosis
Digestive System Diseases
Liver Diseases
Pathologic Processes
Oltipraz
Anthelmintics
Anti-Infective Agents
Anti-Retroviral Agents
Anticarcinogenic Agents
Antineoplastic Agents
Antiparasitic Agents
Antiplatyhelmintic Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Reverse Transcriptase Inhibitors
Schistosomicides
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014