Study to Compare the Efficacy & Safety of Ursoplus Capsules vs. UDCA vs. Placebo Among Chronic Liver Disease Patients

Study Overview
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Brief Summary
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This study aims to compare the efficacy & safety of Ursoplus® capsules (UDCA 250mg & Silymarin 140mg) versus UDCA alone versus Placebo among Compensated Chronic Liver Diseased Patients

Detailed Description
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Research Question: Compare the efficacy & safety of Ursoplus® capsules (UDCA 250mg & Silymarin 140mg) versus UDCA alone versus Placebo among Compensated chronic liver diseased patients Primary Objective: To assess the efficacy of Ursoplus® capsules (UDCA 250mg & Silymarin 140mg) versus UDCA 250mg alone and versus Placebo in the reduction of total serum bilirubin, Direct serum bilirubin and elevated liver Enzymes from baseline to End of Treatment (EOT) Secondary Objectives: To assess the efficacy of Ursoplus® capsules (UDCA 250mg & Silymarin 140mg) versus UDCA 250 mg alone and versus Placebo in reducing the degree of steatosis as measured by Vibration-controlled transient elastography with Controlled Attenuation Parameter (CAP) To assess the safety of Ursoplus® capsules (UDCA 250mg & Silymarin 140mg) versus UDCA 250 mg alone and versus Placebo among compensated Chronic Liver Diseased Patients To describe improvement in quality of life for patients after treatment A study population of 297 patients suffering from compensated chronic Liver Disease, who will be randomized according to Vibration-controlled transient elastography in screening visit into 2 groups: Group 1: with non-cirrhosis, F0, F1 and F2. Group 2: with advanced fibrosis and cirrhosis, F3 and F4. Each group will receive either Ursoplus® capsules (UDCA 250mg & Silymarin 140mg), or UDCA alone or Placebo, through Stratified random sampling. Duration for enrollment: 6 months Total duration of the study/subject will be approximately: 6 months for treatment and follow-up visits including the screening visit Subjects will be enrolled for a duration of 6 months including the screening visit Screening visit 1 (Treatment initiation) Visit 2: after 1st month, follow-up 1 Visit 3: after 2nd month, follow-up 2 Visit 4: after 3rd month, follow-up 3 Visit 5: after 4th month, follow-up 4 Visit 6: after 5th month, follow-up 5 End of Study visit, after 6th month of treatment, follow-up 6

Official Title
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Multi-Center, Randomized, Control, Phase IV Trial to Compare the Efficacy & Safety of Ursoplus® Capsules (UDCA 250mg & Silymarin 140mg) Versus UDCA Alone Versus Placebo Among Compensated Chronic Liver Diseased Patients

Conditions
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Chronic Liver Disease

Intervention / Treatment
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* Drug: Ursoplus
* Drug: UDCA 250mg
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients aged ≥ 18 Subjects with Compensated Chronic Liver Disease, defined as child 5-7. Patients with mild disturbance of liver biochemical profile (elevated Total Serum Bilirubin ≤ 3 mg/dl, or elevated Direct Serum Bilirubin ≤ 2 mg/dl, or elevated one or more of liver enzymes, up to 3 times of the normal level (Alanine Transaminase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) & Gamma Glutamyl Transpeptidase (GGT)). Non-diabetic subjects and subjects with Controlled DM-type 1 and 2 patients, HbA1C up to 7.5% Non-pregnant or lactating female patients Subjects who are willing to sign Informed Consent Form (ICF) and ready to comply with the protocol for the duration of the study Exclusion Criteria: Subjects with a history of hypersensitivity to any of the ingredients of the medications being studied Subjects with positive PCR/or antibodies to Hepatitis C in the past 6 months Subjects with positive hepatitis B surface antigen (HBsAg) Subjects with elevated liver enzymes more than 3 times of the normal level Alanine Transaminase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) & Gamma Glutamyl Transpeptidase (GGT). Subjects with Primary Biliary Cirrhosis (PBC) and Primary Sclerosing Cholangitis (PSC). Subjects with Child Pugh Score more than 7. Subjects with history of bleeding varices. Subjects having uncontrolled Diabetes (HbA1cmore than 7.5 %) Subjects with any medical condition requiring the usage of medication that may interfere with the absorption, distribution, metabolism or excretion of the study drug such as: Bile acid sequestering agents such as cholestyramine and colestipol. Antacids containing aluminum hydroxide. Drugs affecting lipid metabolism such as estrogens, oral and hormonal contraceptives, and clofibrate (and perhaps other lipid-lowering drugs) Subjects who are receiving other liver support drugs (including drugs of the study), 1 month before study initiation. Subjects with auto immune liver disease taking corticosteroid or immune suppressant Pregnant or breast-feeding women Use of oral contraceptives in child bearing ladies

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Group 1: with non-cirrhosis, F0, F1 and F2 Group 2: with advanced fibrosis and cirrhosis, F3 and F4
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ursoplus® capsules (UDCA 250mg & Silymarin 140mg)<br>Ursoplus® capsules: UDCA 250mg & Silymarin 140mg 2 Capsules every 12 hours | Drug: Ursoplus<br>* Ursoplus® capsules (UDCA 250mg & Silymarin 140mg)<br>|
| Active Comparator: UDCA 250mg<br>UDCA capsules: UDCA 250mg 2 Capsules every 12 hours | Drug: UDCA 250mg<br>* UDCA 250mg alone<br>|
| Placebo Comparator: Placebo<br>Placebo alone 2 Capsules every 12 hours | Other: Placebo<br>* Placebo alone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total serum bilirubin | Change in mean Total serum bilirubin from baseline (visit 1) to End of study between the 3 treatment groups | Up to 6 months | 
| Change in Direct Serum Bilirubin | Change in mean Direct Serum Bilirubin from baseline (visit 1) to End of study between the 3 treatment groups | Up to 6 months | 
| Change in Elevated Liver Enzymes | Change in mean AST & ALT from baseline (visit 1) to End of study between the 3 treatment groups | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improved degree of Steatosis | Change in the mean score of Controlled Attenuation Parameter (CAP) from baseline (visit 1) to End of study between the 3 treatment groups, measured by Vibration-controlled transient elastography | Up to 6 months | 
| Improved quality of life | Change in the mean Score of different items of the RAND 36-Item Health Survey between the 3 treatment groups after 3 months (visit 4) and 6 months of treatment (End of study visit). | Up to 6 months | 
| Incidence of adverse events (AEs) | Percent of serious (SAEs)/ non-serious adverse events (AEs), including percent changes in lab tests and percent of AEs leading to permanent discontinuation of the study drug. | Up to 6 months |