Efficacy and Safety Study of TUDCA Compare UDCA to Treatment Chronic Cholestatic Liver Disease-PBC

Beijing Trendful Kangjian Medical Information Consulting

Status and phase: Completed; Phase 3

Conditions: Cholestatic Liver Disease

Treatments: Drug: ursodeoxycholic acid; Drug: tauroursodeoxycholic

Study type: Interventional

Funder types: Other

Identifiers

NCT01829698

2009L05707 (Other Grant/Funding Number)

Trendful-TAU-001

Details and patient eligibility

About

Though ursodeoxycholate acid (UDCA) is the well known effective therapy for PBC,clinical effectiveness of UDCA may be limited by its poor absorption and extensive biotransformation.The more hydrophillic bile acid tauroursodeoxycholate (TUDCA) is the active ingredients of UDCA,and has been approved by state food and drug administration in China for treatment of cholesterol stones.So it is necessary to verify the efficacy and safety of TUDCA in the treatment of adult primary biliary cirrhosis. In this randomized, double-blinded, double -dummy, parallel-controlled and multicenter clinical trial, we detect the proportion of patients who had AKP decline more than 25% as the primary outcome;decline of ALP,total bilirubin, GGT,ALT and AST as secondary outcomes after patients were treated with TUDCA or UDCA for 24 weeks.

Full description

This is a double-blind, randomized, parallel controlled, multicenter, clinical trial. Subjects inclusion by randomization after passing the screening, continuous administration the test drug (Taurolite) or control drug (Ursofalk) treatment for 24 weeks. Compare the safety and efficacy of Taurolite vs Ursofalk.

At the end of the double-blind period，enroll 100 subjects from both two group randomly ,for a consecutive treatment use TUDCA up to 24 weeks. Further evaluate the efficacy and safety of tauroursodeoxycholic acid (TUDCA) in the treatment of adult primary biliary cirrhosis (PBC) for a long time up to one year. Also evaluate the regimen's efficacy and safety that udca take placed by TUDCA in the treatment of adult primary biliary cirrhosis (PBC) for the patients who use udca treatment for 24 weeks.

Enrollment: 199 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 1 Ages Eligible for Study: 18 Years to 70 Years

  2 Alkaline phosphatase (ALP) ≥ 2 times the Upper Limits of Normal (ULN);

  3 Anti mitochondrial antibody (AMA) positive and / or anti-mitochondrial antibody subtype M2 (AMA-M2) positive; if the AMA and AMA-M2 were negative, need liver biopsy confirmed pathological changes in PBC.

Exclusion criteria

• 1．in the 3 months before screening received UDCA, hormones, immunosuppressive therapy;

  2．with extrahepatic biliary obstruction;

  3．accompanied by hepatitis B virus (HBV) and hepatitis C virus (HCV) infection;

  4．laboratory screening examination :

  1. hemoglobin (HB): male< 11 g/dL, female <10 g/dL < g/dL;
  2. the total white blood cell (WBC) count < 3000/mm3;
  3. the absolute neutrophil count (ANC) <1500/mm3;
  4. platelet (PLT) count <50000/mm3;
  5. serum albumin <3.3g/dL;
  6. alanine aminotransferase (ALT) ≥ 10 ULN and / or aspartate aminotransferase (AST) ≥ 10ULN;
  7. ALT ≥ 5 ULN and / or AST ≥ 5 ULN with immunoglobulin G (IgG) ≥ 2ULN;
  8. total bilirubin (T-Bil) ≥ 4 ULN;
  9. prothrombin time (PT) prolonged ≥ 3 seconds (limit reference value based on) or PTA ≤ 60%;
  10. the serum creatinine (Cr) ≥ 1.5ULN.

  5．patients with esophageal variceal or bleeding, ascites, hepatic encephalopathy or other evidence of hepatic decompensation;

  6．diagnosed with liver cancer, suspected to have liver cancer, AFP > 100ng/ml. As the AFP in 2 times the upper limit of normal to 100ng/ml, need re-check in 2 weeks, if their AFP > 100ng/ml can not be included

  7．body mass index >28 (Kg/m2);

  8．alcohol or drug abusers within the recent year;

  9．there is a serious heart, lung, kidney, digestive, nervous, mental disease, autoimmune diseases or malignant tumor

  10．drug-induced liver injury;

  11. plan to transplant or have had organ transplants;

  12． are unable or unwilling to provide informed consent or fails to comply with the test requirements;

  13．pregnant, lactating women.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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199 participants in 2 patient groups

tauroursodeoxycholic

Experimental group

Description:

tauroursodeoxycholic acid, 750mg , divided into three times, each time 250mg, oral administration, after meal

Treatment:

Drug: tauroursodeoxycholic

ursodeoxycholic

Active Comparator group

Description:

control arm: ursodeoxycholic acid, 750mg ,divided into three times, each time 250mg, oral administration, after meal

Treatment:

Drug: ursodeoxycholic acid