Fenofibrate in Combination With Ursodeoxycholic Acid in Primary Biliary Cholangitis

Study Overview
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Brief Summary
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The main objectives of the study were to assess the effects of fenofibrate on serum alkaline phosphatase, as a composite endpoint and on safety in participants with primary biliary cholangitis (PBC)

Official Title
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Fenofibrate in Combination With Ursodeoxycholic Acid in Primary Biliary Cholangitis

Conditions
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Primary Biliary Cholangitis

Intervention / Treatment
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* Drug: Fenofibrate
* Drug: Placebo
* Drug: UDCA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have provided written informed consent Age 18-75 years; BMI 17-28 kg/m2 Male or female with a diagnosis of PBC, by at least two of the following criteria: History of ALP above ULN for at least six months; Positive AMA titers (>1/40 on immunofluorescence or M2 positive by enzyme linked immunosorbent assay (ELISA) or positive PBC-specific antinuclear antibodies; Documented liver biopsy result consistent with PBC. Incomplete response to UDCA defined by 1 x ULN< ALP <= 1.67 x ULN Taking UDCA for at least 6 months (stable dose for ≥ 3 months) prior to Day 0 Exclusion Criteria: History or presence of other concomitant liver diseases. ALT or AST > 5×ULN, TBIL > 3×ULN. If female: known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating. Allergic to fenofibrate or ursodeoxycholic acid. Taking hepatotoxic drugs (e.g., dapsone, erythromycin, fluconazole, ketoconazole, rifampicin) for more than 2 weeks within 6 months, and long-term hormonal users. Recurrent variceal bleeding, poorly controlled hepatic encephalopathy or refractory ascites. Patients with a history of severe cardiac, cerebrovascular, renal, respiratory disease or functional failure, and psychiatric disorders (including those due to alcohol and drug abuse). Creatinine >1.5×ULN and creatinine clearance <60 ml/min. Currently using statins (such as pravastatin, fluvastatin, and simvastatin), other fibrates (such as gemfibrozil and bezafibrate), and drugs structurally similar to fenofibrate (like ketoprofen). Planned to receive an organ transplant or an organ transplant recipient. Needing Liver transplantation within 1 year according to the Mayo Rick score. Any other condition(s) that would compromise the safety of the subject or compromise

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: Fenofibrate-UDCA<br>Fenofibrate 200 mg/day and UDCA 13-15mg/kg/day for 12 months | Drug: Fenofibrate<br>* Fenofibrate 200 mg/day<br>Drug: UDCA<br>* UDCA 13-15mg/kg/day<br>|
| Placebo Comparator: Placebo-UDCA<br>1 tablet/ day and UDCA 13-15mg/kg/day for 12 months | Drug: Placebo<br>* 1 tablet/ day<br>Drug: UDCA<br>* UDCA 13-15mg/kg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with biochemical response | The normalisation of Alkaline Phosphatase | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients having biochemical response | The normalisation of Alkaline Phosphatase at 4, 12, 24, and 36 weeks | 4, 12, 24 and 36weeks | 
| Assessment of the pruritus and fatigue | Change From Baseline in Fatigue and Pruritus as Assessed by Visual Analogue Scale (VAS) Total Score for Fatigue and Pruritus. (0-10, higher scires mean a worse outcome) | 4, 12, 24, 36, and 48 weeks | 
| Percentage of patients having biological or clinical adverse events | Increase of creatinine, blood urea nitrogen, ALT and AST | 4, 12, 24, 36, and 48 weeks | 
| Survival without transplantation and hepatic impairment | Occurrence of ascites, variceal bleeding, hepatic encephalopathy, liver-transplantation, or death | 48 weeks |