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Efficacy of To Be Marketed (TBM) Cholic Acid Capsules Used to Treat Children With Inborn Errors of Bile Acid Synthesis

This study has been completed.
Information provided by (Responsible Party):
Retrophin, Inc. Identifier:
First received: January 19, 2010
Last updated: October 17, 2016
Last verified: July 2016

This is a study in a small population of children who have inborn errors of bile acid synthesis who are currently taking established doses of the currently used cholic acid capsules prepared at the Cincinnati Children's Hospital Pharmacy. The study is designed to compare the efficacy of these currently used capsules with the efficacy of the same treatment provided in a cholic acid capsule that is made by a company that will be marketed after FDA approval.

At baseline, patients receive established doses of cholic acid capsules prepared at the Cincinnati Children's Hospital Medical Center Pharmacy. During the study, patients receive the same treatment provided in the to-be-marketed (TBM) cholic acid capsule. Hence, patients serve as their own controls, with baseline values presenting the reference value (CCHMC cholic acid capsule) and values after 30 days treatment presenting the value for the investigational treatment (TBM cholic acid capsule).

Condition Intervention Phase
Inborn Errors of Bile Acid Synthesis
Drug: Cholic acid
Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open Label, Single Center, Nonrandomized Study Comparing Efficacy of To Be Marketed Cholic Acid With That of the Currently Used Formulation of Cholic Acid Capsules Used to Treat Children With Inborn Errors of Bile Acid Synthesis

Resource links provided by NLM:

Further study details as provided by Retrophin, Inc.:

Primary Outcome Measures:
  • Serum Transaminases [ Time Frame: At baseline and after 30 days of treatment ]
    Concentration of serum alanine transaminase (ALT) and aspartate transaminase (AST)

  • Serum and Urine Bile Acids [ Time Frame: At baseline (BL) and after 30 days of treatment (D30) ]
    Concentration of bile acids in serum (S) and urine (U). (abbreviations: chol.=cholenoic; monohydro=monohydroxy; dihydro=monohydro)

Secondary Outcome Measures:
  • Adverse Events [ Time Frame: Total of 30 days, i.e. from the time point the patients entered into the study up to the end of treatment ]
    Total number of patients with any adverse events

  • Blood Pressure [ Time Frame: At baseline and after 30 days of treatment ]
    Systolic blood pressure (SBP) and diastolic blood pressure (DBP)

  • Physical Examination [ Time Frame: At baseline (BL) and after 30 days of treatment (D30) ]
    Total number of patients with abnormal findings from general physical examination

  • Total Bilirubin [ Time Frame: At baseline and after 30 days of treatment ]
    Concentration of total bilirubin in serum

Enrollment: 16
Study Start Date: April 2010
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cholic Acid Capsule
Manufactured cholic acid capsules
Drug: Cholic acid

The IUPAC name for cholic acid is 3 alpha,7alpha,12 alpha-trihydroxy-5 beta-cholanoic acid. The international nonproprietary name (INN) is cholic acid.

Each patient will be given a box containing a 1 month supply of study drug. Each bottle will contain 90 capsules; each capsule will contain either 50 or 250 mg of manufactured cholic acid depending upon the child's weight. The study drug will be taken orally, in divided doses (as determined by the investigator), for a total daily dose of 10-15 mg/kg body weight. Parents of infants and young children who are unable to swallow the TBM cholic acid capsule will be instructed to sprinkle the contents of the capsule over 1-2 teaspoons of plain applesauce and feed it to the child.

Detailed Description:

Bile acids are end products of cholesterol metabolism. Individuals with inborn errors of bile acid synthesis lack the enzymes needed to synthesize the primary bile acids cholic acid and chenodeoxycholic acid (CDCA). These conditions are serious and account for approximately 1% of cases presenting as idiopathic cholestatic liver disease. The liver disease associated with these inborn errors in bile acid synthesis is progressive and, if untreated, may lead to death from cirrhosis and liver failure.

Monotherapy with cholic acid is considered the most appropriate therapeutic strategy to treat inborn errors in bile acid synthesis because it provides a stimulus for bile flow and inhibits endogenous production and accumulation of potentially hepatotoxic and cholestatic bile acid precursors, while additionally facilitating the absorption of fats and fat-soluble vitamins. At therapeutic doses, adverse effects are not generally observed and as such, cholic acid has become the treatment of choice at the Cincinnati Children's Hospital since 1994.

This study will bridge data on the effectiveness of a standardized manufactured preparation to data obtained from patients originally treated with the currently used cholic acid capsules formulated in the CCHMC Pharmacy before being switched to the manufactured preparation.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • must have stable transaminase levels within 2 times the upper limits of the normal range.
  • must have a diagnosis of an inborn error of bile acid synthesis.
  • must have signed the written informed consent/assent document before study start.
  • must be currently receiving currently used cholic acid therapy under IND 45,470.
  • must be willing and able to comply with all study assessments and procedures.
  • must be able to make two visits (Visit 1 and Visit 2) to the study site.

Exclusion Criteria:

  • is not currently receiving cholic acid therapy for inborn errors of bile acid synthesis under IND 45,470.
  • is unable or unwilling to comply with study requirements.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01115582

United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Retrophin, Inc.
Principal Investigator: James E Heubi, MD Children's Hospital Medical Center, Cincinnati
  More Information

Jacquemin E., Gerhardt M, Cresteil D, Fabre M, Taburet AM, Hadchouel M, Trivin F, Stechell KDR and Bernard O. Long-term effects of bile acid therapy in children with defects of primary bile acid synthesis: 3ß-Hydroxy-C27-steroid dehydrogenase/isomerase and Delta4-3-Oxosteroid 5ß-reductase deficiencies. In: van Berge Henegouwen GP, et al. (eds): Falk Symposium No 120: Biology of Bile Acids in Health and Disease. Kluwer Academic Publishers, Dordrecht/Boston/London; 2001:278-282.
Setchell KDR, et al. A unique case of cerebrotendinous xantomatosis presenting in infancy with cholestatic liver disease further highlights bile acid synthetic defects as an important category of metabolic liver disease. In: van Berge Henegouwen GP et al. (ed): Falk Symposium No. 120: Biology of Bile Acids in Health and Disease. Boston: Kluwer Academic Publishers; 2001.

Responsible Party: Retrophin, Inc. Identifier: NCT01115582     History of Changes
Other Study ID Numbers: CAC-001-01
Study First Received: January 19, 2010
Results First Received: July 20, 2016
Last Updated: October 17, 2016

Keywords provided by Retrophin, Inc.:
Inborn Errors
Bile Acid
Liver Disease

Additional relevant MeSH terms:
Bile Acids and Salts
Cholic Acids
Gastrointestinal Agents processed this record on May 25, 2017