Study of Obeticholic Acid（OCA） Combination With Ursodeoxycholic Acid (UDCA) in Patients With Primay Biliary Cirrhosis (PBC)

Study Overview
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Brief Summary
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Obecholic acid is a modified bile acid and Farnesoid X receptor (FXR) agonist. FXR is a key regulator of bile acid synthesis and transport. Bile acids are used by the body to help with digestion. Conventional therapy with obecholic acid will improve liver function of patients with PBC.

Official Title
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A Multi-center, Randomized, Double-blind Trail Evaluating the Efficacy and Safety of Combination of Obecholic Acid and UDCA Compared With UDCA Monotherapy in PBC Patients With an Inadequate Response to UDCA .

Conditions
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Primary Biliary Cirrhosis

Intervention / Treatment
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* Drug: Obeticholic Acid Tablets
* Drug: UDCA
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18 to 75 years. Meet at least 2 of the following 3 PBC diagnoses: Patients had elevated alkaline phosphatase for at least 3 months before enrolment. AMA positive (titer ≥1:40), or if AMA negative, PBC specific antibodies (anti- GP210 and/or anti-SP100 and/or AMA-M2) are required. Liver biopsy suggested PBC 48 weeks before enrollment. ALP > 1.67× ULN before enrollment. Taking UDCA with stable dose for at least 3 months before enrollment. Exclusion Criteria: Merging with other virus infected. With other existing liver disease or a history of liver disease. With clinical complications of PBC or clinically significant hepatic decompensation. Child-pugh grade B or C. Creatinine (Cr) ≥ 1.5×ULN and serum creatinine clearance rate < 60mL/min; [Calculation formula: Cr:(140-age)×weight(kg) /0.818 × Scr (μmol/L)，female Cr=Cr × 0.85]. ALT or AST>5×ULN;Tbil > 2×ULN. Patients with a history of severe pruritus 2 months before enrollment. The presence of clinically relevant arrhythmias or associated history that may affect survival during the study period. With diseases that may cause nonhepatic ALP increases (e.g., Paget's disease) or which may diminish life expectancy to < 2 years.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OCA Tablets 5-10 mg<br>OCA 5 mg once daily in combination with UDCA for 24 weeks and then titrating up to 10 mg based on tolerability and response for remainder of double-blind period. | Drug: Obeticholic Acid Tablets<br>* Obeticholic Acid：Once a day (QD) by mouth (PO).<br>Drug: UDCA<br>* UDCA：continue prestudy dose<br>|
| Placebo Comparator: Placebo<br>Placebo once daily in combination with UDCA for 48 weeks. | Drug: UDCA<br>* UDCA：continue prestudy dose<br>Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of PBC patients reaching the compound endpoint after 48 weeks of treatment (Compound endpoint: alkaline phosphatase (ALP) < 1.67× Upper Limit of Normal(ULN), ALP decrease by at least 15% , and total bilirubin ≤ ULN ) | Compound endpoint: ALP < 1.67× ULN, ALP decrease by at least 15% , and total bilirubin ≤ ULN | up to 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of PBC patients reaching the compound endpoint after 4 weeks, 12 weeks, 24 weeks and 36 weeks of treatment (Compound endpoint: ALP < 1.67× ULN, ALP decrease by at least 15% , and total bilirubin ≤ ULN ) | Compound endpoint: ALP < 1.67× ULN, ALP decrease by at least 15% , and total bilirubin ≤ ULN | up to 36 weeks | 
| Rate of change of liver function indicators from baseline | Liver function: ALP (alkaline phosphatase ), ALT (Alaninetransaminase), AST(aspartate transaminase), GGT( γ-glutamyl transpeptadase ), TBA (total bile acid) and Tbil (total bilirubin) | up to 48 weeks |