I. To Evaluate the therapeutic efficacy of cholic acid during provision of compassionate
treatment to patients with identified inborn errors of bile acid synthesis and metabolism
II. To assess the safety and tolerability of cholic acid
A Phase III, open label, single arm, nonrandomized, non-comparative, compassionate treatment
study of cholic acid in the treatment of defects of bile acid metabolism.
The study was begun with a single study site at Cincinnati Children's Hospital Medical
Center (CCHMC), but in 2005 was expanded so that compassionate treatment could be provided
to additional patients who had been identified with inborn errors of bile metabolism through
the center's screening/diagnostic program.
Patients who were screened were contacted and evaluated with respect to the
inclusion/exclusion criteria. Signed informed consent by the patient and/or parents/legal
guardian was obtained as soon as it is confirmed that the patient met inclusion/exclusion
criteria and the parents/guardian would agree for the child to participate in the study.
The primary interventions for the study were:
1. Administration of study drug.
2. Collection of baseline physical exam, vital signs, blood and urine samples for
3. Collection of periodic physical exam, vital signs, blood and urine samples for
laboratory tests during the period of administration of the study drug.
4. Collection of any adverse event information.
Time and Events Schedule:
1. Confirm eligibility
2. Obtain written informed consent from patient and/or parents/legal guardian
3. Collect demographic data and disease and medication history, including family history
Baseline and Ongoing:
4. Obtain body weight
5. Record adverse events
6. Obtain blood and urine samples for laboratory tests
7. Initiate study drug therapy & monitor study drug therapy and adjust dose as needed
PROTOCOL ENTRY CRITERIA:
Clinical or biochemical evidence of liver disease, unexplained fat-soluble vitamin
malabsorption, or peroxisomal dysfunction that compromises bile acid biosynthesis
Inclusion criteria for enrollment were:
- Infants < age 3 months
- Children presenting for evaluation of cholestasis defined as a conjugated bilirubin >
2mg/dl or increased serum bile acids
- Older subjects of any age with cholestatic liver disease if urine screens suggested
that they had inborn errors of bile acid metabolism
- Confirmation of a diagnosis of an inborn error of bile acid synthesis based upon
urine analysis by FAB-MS to determine whether specific abnormalities in bile acid
synthesis are indicated
- The patient and/or parent/legal guardian must have signed the written informed
consent document before study start.
- The patient must be willing and able to comply with all study assessments and