Primary Biliary Cirrhosis
Conditions
Keywords
PBC, Primary Biliary Cirrhosis, Fenofibrate, Triglide
Brief summary
This is a pilot study to evaluate the safety and efficacy of fenofibrate on patients with primary biliary cirrhosis who have an incomplete response to ursodeoxycholic acid.
Detailed description
This is a multicenter open label pilot study to evaluate the efficacy of fenofibrate in 20 patients with PBC treated for 1 year. A randomized design would not be feasible at this stage of the research. Two sites are enrolling patients: University of Florida, Gainesville, and Mayo Clinic Rochester, with the first as the coordinating site. The total number of patients to start treatment will not exceed 20. Our endpoints are 1) surrogate markers of disease activity -serum alkaline phosphatase and immunoglobulin M; 2) a well validated prognostic index -Mayo risk score and 3) the NIDDK quality of life questionnaire.
Interventions
DRUGFenofibrate IDD-P (Insoluble Drug Delivery-Micro Particle)
160 mg per day for 1 year
Sponsors
The PBCers Organization
Shionogi Inc.
University of Florida
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Established diagnosis of PBC by serological (positive antimitochondrial antibodies) and/or histological evidence (diagnostic liver biopsy) * Previous treatment with UDCA 13-15 mg/kg/day for at least 1 year * Persistent elevation of serum alkaline phosphatase ≥ 2 times the upper limit of normal on two separate measurements * Female patients of childbearing age should have a pregnancy test done within -days of the beginning of this trial, and should agree to be on adequate contraception throughout the study period * Signed informed consent after careful review of the information and study details by one of the investigators
Exclusion criteria
* Hypersensitivity to fenofibrate * Prisoners and institutionalized subjects * Pregnant or nursing women * Anticipated need for liver transplantation in one year (estimated one year survival \< 80%) as determined by the Mayo risk score. The Mayo risk score takes into account the patient's age, serum bilirubin, albumin and prothrombin time, as well as presence or absence of peripheral edema. * Recipients of liver transplantation * Recurrent variceal hemorrhage, uncontrolled encephalopathy or refractory ascites * Co-existing liver diseases, such as primary sclerosing cholangitis, acute or chronic hepatitis, alcoholic liver disease, choledocholithiasis, autoimmune hepatitis, cholangiocarcinoma * Acute or chronic renal failure * Known history of cholecystitis with intact gallbladder * Current use of statins, as the concomitant use of fibrates and statins would increase the risk of toxicity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Level of Alkaline Phosphatase | 1 year | We analyzed whether there was a difference in median ALP at 1 year compared to baseline values. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from the liver clinics at University of Florida and Mayo Clinic Rochester.
Participants by arm
| Arm | Count |
|---|---|
| Patients Treated With Fenofibrate Fenofibrate IDD-P (Insoluble Drug Delivery-Micro Particle) 160 mg per day | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Patients Treated With Fenofibrate |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Age, Continuous | 54 years STANDARD_DEVIATION 8.9 |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 20 |
| serious Total, serious adverse events | 1 / 20 |
Outcome results
Primary
Serum Level of Alkaline Phosphatase
We analyzed whether there was a difference in median ALP at 1 year compared to baseline values.
Time frame: 1 year
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Patients Before Treatment With Fenofibrate | Serum Level of Alkaline Phosphatase | 351 U/L |
| Patients Treated With Fenofibrate | Serum Level of Alkaline Phosphatase | 175 U/L |
Comparison: Sample size calculation estimated that with 20 patients, and assuming a 10% drop-out rate, the study would have 80% power to detect a response rate in 35% or more of the study patients. A two-sided p value\<0.05 was considered statistically significant.p-value: <0.0001Wilcoxon (Mann-Whitney)