The primary purpose of the study is to evaluate the therapeutic efficacy and safety of cholic acid in subjects with identified inborn errors of bile acid synthesis.
This is a Phase 3, open-label, single center, nonrandomized study. This continuation protocol will consist of eligible subjects who have previously received cholic acid through the Cincinnati Children's Hospital Medical Center (CCHMC) Compassionate Use (91-10-10), CAC-001-01 study protocols and newly diagnosed subjects. New subjects will be infants, children, adolescents identified from urine samples obtained from the clinical services of programs across the U.S., Canada, South America, Europe, and Asia. Subject or their legal representative will receive information regarding the study, and the principle investigator (PI) or designee will obtain informed consent. Serum and urine samples will be collected and sent to CCHMC to measure complete bile acid profile analysis. Clinical records including medical history, physical exams, vital signs, and laboratory assessments performed as standard of care will be reviewed to ensure subject eligibility and determine baseline values. Subjects who have participated in Protocols conducted under IND 45,470 will be consented to continue to receive cholic acid capsules under this continuation protocol. Subjects will serve as their own controls and no placebo will be utilized.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
53
10-15 mg/kg body weight/day supplied in 50 or 250 mg Cholic Acid Capsules
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Change in Atypical Urinary Bile Acid Excretion by FAB-MS (Fast-Atom-Bombardment Ionization-Mass Spectrometry)
The level of atypical urinary bile acid secretion was scored using a scale of: 0, normal; 1, slight; 2, significant; or 3, marked. A Cochran-Mantel-Haenszel (CMH) test with modified ridit scoring was used to compare the difference between the score at baseline and the worst post-baseline score during treatment with cholic acid in this single-arm trial.
Time frame: At baseline, then every 12 months for an average of 3.5 years
Evaluation of Serum Transaminases: ALT
Changes in ALT were evaluated in terms of elevations above the upper limit of normal (ULN) and were categorized as: \<ULN; ≥1 ULN but \<2 ULN; ≥2 ULN but \<3 ULN; and ≥3x ULN. Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial were presented.
Time frame: At baseline, then every 12 months for an average of 3.5 years
Evaluation of Serum Transaminases: AST
Changes in AST were evaluated in terms of elevations above the upper limit of normal (ULN) and were categorized as: \<ULN; ≥1 ULN but \<2 ULN; ≥2 ULN but \<3 ULN; and ≥3x ULN. Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial were presented.
Time frame: At baseline, then every 12 months for an average of 3.5 years
Clinical Laboratory Results: Bilirubin
Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial for bilirubin. Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial were presented in terms of descriptive statistics.
Time frame: At baseline, then every 12 months for an average of 3.5 years
Clinical Laboratory Results: Gamma Glutamyl Transferase (GGT)
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Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial for GGT. Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial were presented in terms of descriptive statistics.
Time frame: At baseline, then every 12 months for an average of 3.5 years
Clinical Laboratory Results: Alkaline Phosphatase
Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial for alkaline phosphatase. Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial were presented in terms of descriptive statistics.
Time frame: At baseline, then every 12 months for an average of 3.5 years
Clinical Laboratory Results: Prothrombin Time
Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial for prothrombin time. Changes from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial were presented in terms of descriptive statistics.
Time frame: At baseline, then every 12 months for an average of 3.5 years
Physical Examinations: Height
Changes in height percentiles from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial.
Time frame: At baseline, then every 12 months for an average of 3.5 years
Physical Examinations: Body Weight
Changes in body weight percentiles from baseline to the worst post-baseline value during treatment with cholic acid in this single-arm trial.
Time frame: At baseline, then every 12 months for an average of 3.5 years
Incidence of Adverse Events
Number (%) of patients with any AE
Time frame: At baseline, then every 12 months for an average of 3.5 years