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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Evaluate the Efficacy And Safety Of TUDCA Compare UDCA In The Treatment Of Cholestatic Liver Disease-PBC by A Randomized,Double-Blind,Double Dummy,Parallel-Controlled,Multicenter Trial and The Consecutive Treatment By TUDCA

Conditions
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Cholestatic Liver Disease

Intervention / Treatment
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* Drug: tauroursodeoxycholic
* Drug: ursodeoxycholic acid


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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tauroursodeoxycholic<br>tauroursodeoxycholic acid, 750mg , divided into three times, each time 250mg, oral administration, after meal | Drug: tauroursodeoxycholic<br>* Testing arm: tauroursodeoxycholic acid, 750mg , divided into three times, each time 250mg, oral administration, after meal<br>* Other names: Taurolite;|
| Active Comparator: ursodeoxycholic<br>control arm: ursodeoxycholic acid, 750mg ,divided into three times, each time 250mg, oral administration, after meal | Drug: ursodeoxycholic acid<br>* ursodeoxycholic acid, 750mg ,divided into three times, each time 250mg, oral administration, after meal<br>* Other names: Ursofalk;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficiency is defined as the patients composition whose ALP level of serum decreased more than 25% compared to baseline at treatment for 24 weeks. | After 24 weeks of treatment, calculate the rate of patients whose ALP level of serum ALP decreased more than 25% compared to the baseline. After 48 weeks of treatment, calculate the rate of patients whose ALP level of serum ALP decreased more than 40% compared to the baseline. | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of laboratory parameters about liver function | after 24 weeks of treatment, the serum level ALP decreased compared with baseline. after 24 weeks of treatment, the serum bilirubin level decreased compared with baseline. after 24 weeks of treatment, the serum level of GGT decreased compared with baseline. after 24 weeks of treatment, serum ALT, AST levels decreased compared to baseline. after 48 weeks of treatment, the serum level ALP decreased compared with 24 weeks. after 48 weeks of treatment, the serum level ALP decreased compared with baseline. after 48 weeks of treatment, the serum bilirubin level decreased compared with 24 weeks. after 48 weeks of treatment, the serum level of GGT decreased compared with 24 weeks. after 48 weeks of treatment, serum ALT, AST levels decreased compared to 24 weeks. | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tudca PBC Cholestasis tauroursodeoxycholic acid taurolite