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

NCT01115582 | Completed Phase 3 Results

• 1 other identifier: CAC-001-01
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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).

Conditions

Inborn Errors of Bile Acid Synthesis

Keywords

Inborn Errors; Bile Acid; Pediatrics; Liver Disease

Outcome Measures

Primary Outcomes (2)

• Serum Transaminases

  Concentration of serum alanine transaminase (ALT) and aspartate transaminase (AST)

  At baseline and after 30 days of treatment

• Serum and Urine Bile Acids

  Concentration of bile acids in serum (S) and urine (U). (abbreviations: chol.=cholenoic; monohydro=monohydroxy; dihydro=monohydro)

  At baseline (BL) and after 30 days of treatment (D30)

Secondary Outcomes (4)

• Adverse Events

  Total of 30 days, i.e. from the time point the patients entered into the study up to the end of treatment

• Blood Pressure

  At baseline and after 30 days of treatment

• Physical Examination

  At baseline (BL) and after 30 days of treatment (D30)

• Total Bilirubin

  At baseline and after 30 days of treatment

Study Arms (1)

Cholic Acid Capsule

EXPERIMENTAL

Manufactured cholic acid capsules

Drug: Cholic acid

Interventions

Cholic acid 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.

Cholic Acid Capsule

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mirum Pharmaceuticals, Inc.: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (6)

• 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.

  PMID: 15383928 BACKGROUND

• 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.

  PMID: 19622360 BACKGROUND

• 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.

  PMID: 17682975 BACKGROUND

• 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.

  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.

  PMID: 16819396 BACKGROUND

• 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.

  BACKGROUND

MeSH Terms

Conditions

Liver Diseases

Interventions

Cholic Acid

Condition Hierarchy (Ancestors)

Digestive System Diseases

Intervention Hierarchy (Ancestors)

Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes

Results Point of Contact

• Title: Retrophin Medical Information
• Organization: Retrophin, Inc.

medinfo@retrophin.com

1-877-659

Study Officials

• James E Heubi, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2010
• First Posted: May 4, 2010
• Study Start: April 1, 2010
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: October 3, 2023
• Results First Posted: December 9, 2016

Record last verified: 2023-09

Locations

US (1)