Study of INT 747 in Combination With URSO in Patients With Primay Biliary Cirrhosis (PBC)

Study Overview
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Brief Summary
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The primary hypothesis is that INT-747 will cause a reduction in alkaline phosphatase levels in Primary Biliary Cirrhosis patients, over a 12 week treatment period, as compared to placebo.

Detailed Description
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None provided

Official Title
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A Study of INT 747 (6α-ethyl Chenodeoxycholic Acid (6-ECDCA)) in Combination With Ursodeoxycholic Acid (URSO®, UDCA) in Patients With Primary Biliary Cirrhosis

Conditions
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Liver Cirrhosis, Biliary

Intervention / Treatment
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* Drug: INT-747
* Drug: Ursodeoxycholic Acid (URSO)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female age 18 to 70 years. Stable dose of ursodeoxycholic acid (URSO, UDCA) for at least 6 months prior to screening. Female patients must be postmenopausal, surgically sterile, or prepared to use 2 methods of contraception with all sexual partners during the study and for 14 days after the end of dosing. Male patients must be prepared to use 2 methods of contraception with all sexual partners during the study and for 14 days after the end of the dosing. Proven or likely PBC, as demonstrated by the patient presenting with at least 2 of the following 3 diagnostic factors: History of increased AP levels for at least 6 months prior to Day 0 Positive AMA titer (>1:40 titer on immunofluorescence or M2 positive by ELISA) or PBC-specific antinuclear antibodies (antinuclear dot and nuclear rim positive) Liver biopsy consistent with PBC. Screening AP value between 1.5 and 10 × ULN. Exclusion Criteria: Administration of the following drugs at any time during the 3 months prior to screening for the study: colchicine, methotrexate, azathioprine, or systemic corticosteroids. Screening conjugated (direct) bilirubin >2 × ULN. Screening ALT or AST >5 × ULN. Screening serum creatinine >1.5 mg/dL (133 mol/L). History or presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy, or poorly controlled ascites). History or presence of other concomitant liver diseases including hepatitis due to hepatitis B or C virus (HCV, HBV) infection, primary sclerosing cholangitis (PSC), alcoholic liver disease, definite autoimmune liver disease or biopsy proven nonalcoholic steatohepatitis (NASH). Pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INT-747 10 mg<br>INT-747 10 mg once daily in combination with URSO for 12 weeks. | Drug: INT-747<br>* Once a day (QD) by mouth (PO)<br>* Other names: Obeticholic acid (OCA), 6-ECDCA;Drug: Ursodeoxycholic Acid (URSO)<br>* Stable dose for at least 6 months prior to screening. Dose as prescribed by physician.<br>* Other names: URSO, UDCA;|
| Experimental: INT-747 25 mg<br>INT-747 25 mg once daily in combination with URSO for 12 weeks. | Drug: INT-747<br>* Once a day (QD) by mouth (PO)<br>* Other names: Obeticholic acid (OCA), 6-ECDCA;Drug: Ursodeoxycholic Acid (URSO)<br>* Stable dose for at least 6 months prior to screening. Dose as prescribed by physician.<br>* Other names: URSO, UDCA;|
| Experimental: INT-747 50 mg<br>INT-747 50 mg once daily in combination with URSO for 12 weeks. | Drug: INT-747<br>* Once a day (QD) by mouth (PO)<br>* Other names: Obeticholic acid (OCA), 6-ECDCA;Drug: Ursodeoxycholic Acid (URSO)<br>* Stable dose for at least 6 months prior to screening. Dose as prescribed by physician.<br>* Other names: URSO, UDCA;|
| Placebo Comparator: Placebo<br>Placebo once daily in combination with URSO for 12 weeks. | Drug: INT-747<br>* Once a day (QD) by mouth (PO)<br>* Other names: Obeticholic acid (OCA), 6-ECDCA;Drug: Ursodeoxycholic Acid (URSO)<br>* Stable dose for at least 6 months prior to screening. Dose as prescribed by physician.<br>* Other names: URSO, UDCA;Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alkaline Phosphatase (ALP). | The primary efficacy endpoint was the relative (%) change in plasma ALP from pretreatment values. The prestudy consensus opinion of the investigators was that a placebo-substracted ALP fall of ≥ 10% would be clinically significant. | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Gamma-Glutamyl Transpeptidase (GGT) | Percent change in serum gamma-glutamyl transpeptidase (GGT) from baseline to Day 85/early termination. | Baseline and 12 weeks | 
| Alanine Aminotransferase (ALT) | Mean percent change in serum alanine aminotransferase (ALT) from baseline to Day 85/early termination. | Baseline and 12 weeks | 
| Plasma Trough Concentrations of INT-747 and Its Major, Known Metabolites |  | 12 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PBC, Primary Biliary Cirrhosis, Liver,