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

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

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.

Study Overview

• Status: Completed
• Conditions: Cholestatic Liver Disease
• Intervention / Treatment: Drug: tauroursodeoxycholic; Drug: ursodeoxycholic acid

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 199
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Liver Research Center,Beijing Friendship Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tauroursodeoxycholic; tauroursodeoxycholic acid, 750mg , divided into three times, each time 250mg, oral administration, after meal	Drug: tauroursodeoxycholic; Testing arm: tauroursodeoxycholic acid, 750mg , divided into three times, each time 250mg, oral administration, after meal; Other Names: Taurolite; TUDCA
Active Comparator: ursodeoxycholic; control arm: ursodeoxycholic acid, 750mg ,divided into three times, each time 250mg, oral administration, after meal	Drug: ursodeoxycholic acid; ursodeoxycholic acid, 750mg ,divided into three times, each time 250mg, oral administration, after meal; Other Names: UDCA; Ursofalk

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Beijing Trendful Kangjian Medical Information Consulting Limited Company
• Investigators: Principal Investigator: Ji Dong Jia, Doctor, Beijing Friendship Hospital; Study Director: Wen Xie, Doctor, Beijing Ditan Hospital; Study Director: Hui Ping Yan, Doctor, Beijing Youan Hospital; Study Director: Guo Feng Chen, Doctor, Beijing 302 Hospital; Study Director: Gui Qiang Wang, Doctor, Peking University First Hospital; Study Director: Lai Wei, Doctor, Peking University People's Hospital; Study Director: Liu Fang Cheng, Doctor, Chinese PLA General Hospital; Study Director: Min De Zeng, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine; Study Director: Qing Xie, Doctor, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine; Study Director: Guang Feng Shi, Doctor, Affiliated HuaShan Hospital of Fudan University; Study Director: Ji Yao Wang, Doctor, Affiliated Zhongshan Hospital of Fudan University; Study Director: Xiao Hui Miao, Doctor, Shanghai Changzheng Hospital; Study Director: Cheng Wei Chen, Doctor, No.85 Hospital of PLA; Study Director: Shan Ming Wu, Doctor, Shanghai Public Health Clinical Center; Study Director: He Ping Hu, Doctor, Shanghai Eastern Hepatobiliary Surgery Hospital; Study Director: Min Hu Chen, Doctor, The First Affiliated Hospital,SunYat-Sen University; Study Director: Zhi Liang Gao, Doctor, The Third Affiliated Hospital,SUNYAT-SEN UNIVERSITY; Study Director: Jin Lin Hou, Doctor, Affiliated Southern Hospital of Southern Medical University; Study Director: Ji Fang Sheng, Doctor, The First Affiliated Hospital of Medical College,Zhejiang University; Study Director: Xiao Qing Fu, Doctor, NO.6 People's Hospital of Hangzhou; Study Director: Hong Tang, Doctor, Affiliated Huaxi Hospital of Sichuan University; Study Director: Ying Han, Doctor, The First Affiliated Hospital of the Fourth Military Medical University; Study Director: Qin Ning, Doctor, Affiliated TongJi Hospital Of Tongji Medical College Huazhong University Of Science&Technology; Study Director: Li Ping Duan, Doctor, The First Affiliated Hospital of Kunming Medical College; Study Director: Jie Xu, Doctor, NO.3 People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: April 9, 2013
• First Submitted That Met QC Criteria: April 10, 2013
• First Posted (Estimate): April 11, 2013

Study Record Updates

• Last Update Posted (Estimate): March 24, 2014
• Last Update Submitted That Met QC Criteria: March 21, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: tudca PBC Cholestasis tauroursodeoxycholic acid taurolite
• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Liver Diseases; Cholestasis; Gastrointestinal Agents; Cholagogues and Choleretics; Ursodeoxycholic Acid
• Other Study ID Numbers: Trendful-TAU-001; 2009L05707 (SFDA)