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

NCT ID: NCT01115582

Last Updated: 2023-10-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2010-08-31

Brief Summary

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).

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.

Conditions

Inborn Errors of Bile Acid Synthesis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cholic Acid Capsule

Manufactured cholic acid capsules

Group Type: EXPERIMENTAL

Cholic acid

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mirum Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James E Heubi, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Locations

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Countries

United States

References

Bove KE, Heubi JE, Balistreri WF, Setchell KD. Bile acid synthetic defects and liver disease: a comprehensive review. Pediatr Dev Pathol. 2004 Jul-Aug;7(4):315-34. doi: 10.1007/s10024-002-1201-8. Epub 2004 Jul 15.

Reference Type: BACKGROUND

PMID: 15383928 (View on PubMed)

Gonzales E, Gerhardt MF, Fabre M, Setchell KD, Davit-Spraul A, Vincent I, Heubi JE, Bernard O, Jacquemin E. Oral cholic acid for hereditary defects of primary bile acid synthesis: a safe and effective long-term therapy. Gastroenterology. 2009 Oct;137(4):1310-1320.e1-3. doi: 10.1053/j.gastro.2009.07.043. Epub 2009 Jul 19.

Reference Type: BACKGROUND

PMID: 19622360 (View on PubMed)

Heubi JE, Setchell KD, Bove KE. Inborn errors of bile acid metabolism. Semin Liver Dis. 2007 Aug;27(3):282-94. doi: 10.1055/s-2007-985073.

Reference Type: BACKGROUND

PMID: 17682975 (View on PubMed)

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.

Reference Type: BACKGROUND

Setchell KD, Heubi JE. Defects in bile acid biosynthesis--diagnosis and treatment. J Pediatr Gastroenterol Nutr. 2006 Jul;43 Suppl 1:S17-22. doi: 10.1097/01.mpg.0000226386.79483.7b.

Reference Type: BACKGROUND

PMID: 16819396 (View on PubMed)

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.

Reference Type: BACKGROUND

Other Identifiers

CAC-001-01

Identifier Type: -

Identifier Source: org_study_id