Biliary atresia MedDRA version: 20.0 Level: LLT Classification code 10004653 Term: Biliary atresia System Organ Class: 100000004850 MedDRA version: 20.1 Level: LLT Classification code 10004654 Term: Biliary atresia, congenital System Organ Class: 100000004850
Conditions
Interventions
Product Name: OCA 1.5mg
Product Code: OCA
Pharmaceutical Form: Tablet
INN or Proposed INN: obeticholic acid
CAS Number: 459789-99-2
Current Sponsor code: OCA
Concentration unit: mg milligram(s)
Concen
Sponsors
Intercept Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female pediatric subjects, aged =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Prior liver transplant or active status on transplant list 2. Complications of decompensated cirrhosis including: a. Total bilirubin =2 mg/dL (34.2 µmol/L) b. Platelets <40,000/µL c. INR =2 d. Recent (within the previous 6 months prior to Screening) bleeding from gastroesophageal varices e. Recent (within the previous 6 months prior to Screening) uncontrolled ascites (diuretic resistant) f. Hepatic encephalopathy g. Prior placement of portosystemic shunt h. Diagnosis of hepatopulmonary syndrome or portopulmonary hypertension 3. Current intractable pruritus or those requiring systemic treatment for pruritus within 3 months of Screening (eg, with bile acid sequestrants or rifampicin) 4. Subjects aged <2 years 5. Subjects weighing <11 kg.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Safety and tolerability - Pharmacokinetics (PK) of OCA and its conjugates o SD Phase: To assess the PK of low dose OCA and its conjugates and to determine the appropriate dose of OCA in the MD Phase o MD Phase: To assess the PK of a range of OCA doses and its conjugates after a single dose and at steady state;Secondary Objective: - Pharmacodynamics (PD) of OCA as measured by markers of farnesoid X receptor (FXR) activation, hepatobiliary indices of liver function, and levels of vitamins A and D (MD Phase only);Primary end point(s): Safety and tolerability - Treatment-emergent adverse events (TEAEs) including serious AEs (SAEs), electrocardiogram (ECG), physical exam, clinical laboratory results, vital signs. PK - Plasma concentrations of unconjugated OCA, its conjugates (glycine conjugate of OCA [glyco-OCA] and taurine conjugate of OCA [tauro-OCA]) and total OCA after SD and MD Phases. ;Timepoint(s) of evaluation of this end point: Safety and tolerability - TEAEs & vital signs taken from Screening to End of study - ECG taken at screening, day 78, End of study - Physical exam taken at screening, day -1, 28, 56, 78, end of study - Clinical laboratory results at screening, day -1, 2, 14, 21, 28, 42,56, 77,end of study PK PK sampling on days 1, 2, 7, 14 in single dose phase; day 21, 22, 42, 43, 56, 77, 78, EOT in multiple dose phase. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PD: Hepatobiliary indices and vitamins A and D - Alkaline phosphatase (ALP), AST, ALT, gamma glutamyl transferase (GGT), total and direct (conjugated) bilirubin, vitamins A and D. PD: Markers of FXR activation - Fibroblast growth factor (FGF-19), 7-hydroxy-4-cholesten-3-one (C4), and endogenous bile acids.;Timepoint(s) of evaluation of this end point: PD: Hepatobiliary indices and vitamins A and D - ALP, AST, ALT, GGT, total and direct (conjugated) bilirubin taken at screening, day -1, 2, 14, 21, 28, 42, 56, 77, end of study - Vitamins A and D taken at screening, day 77, EOT PD: Markers of FXR activation - FGF-19, C4, and endogenous bile acids taken at day 1, 56, 77 | — |
Countries
Belgium, Finland, Germany, Italy, Netherlands, United Kingdom, United States
Contacts
Public ContactProject Management
Syneos Health UK Limited
Outcome results
None listed