Compassionate Treatment of Patients With Inborn Errors of Bile Acid Metabolism With Cholic Acid
Compassionate Treatment of Patients With Inborn Errors of Bile Acid Metabolism With Cholic Acid
OBJECTIVES:

 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
Investigational Plan:

 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
 laboratory tests.

 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:

 Baseline:

 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:

 --Disease Characteristics--

 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
 procedures.