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

NCT00007020 | Completed Phase 3 Results

• 3 other identifiers: CAC-91-10-10CCHMC-91-10-10NCRR-M01RR08084-0009
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Infantile Refsum's Disease; Zellweger Syndrome; Adrenoleukodystrophy; Peroxisomal Disorders; Cholestasis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Excretion of Atypical Bile Acids in Urine by Category

  Patients with excretion of atypical bile acids in urine by category, from worst status before treatment (baseline, BL) to best status on treatment (OT)

  Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years

Secondary Outcomes (4)

• Change in Liver Function Tests (LFTs) Measured in Serum

  Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years

• Liver Histology

  At baseline (if no historical data were available) and between 1 and 6 months following treatment start.

• Height and Weight

  Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years

• Adverse Events

  Baseline, then every 1, 3, or 6 months (depending on protocol version) for an average of 2.8 years

Other Outcomes (1)

• Change in Bilirubin Measured in Serum

  Baseline and on treatment (every 1, 3, or 6 months, depending on protocol version, for an average of 2.8 years)

Study Arms (1)

Cholic Acid

OTHER

Drug: Cholic Acids

Interventions

Cholic Acids DRUG

10-15 mg/kg body weight/day taken orally.

Also known as: Cholic, Cholic Acid, Cholic Acid Capsules

Cholic Acid

Eligibility Criteria

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

You may qualify if:

• 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.

Sponsors & Collaborators

• Mirum Pharmaceuticals, Inc.: lead
• Children's Hospital Medical Center, Cincinnati: collaborator

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Related Publications (1)

• Heubi JE, Bove KE, Setchell KDR. Oral Cholic Acid Is Efficacious and Well Tolerated in Patients With Bile Acid Synthesis and Zellweger Spectrum Disorders. J Pediatr Gastroenterol Nutr. 2017 Sep;65(3):321-326. doi: 10.1097/MPG.0000000000001657.

  PMID: 28644367 DERIVED

MeSH Terms

Conditions

Refsum Disease, Infantile; Zellweger Syndrome; Adrenoleukodystrophy; Peroxisomal Disorders; Cholestasis

Interventions

Cholic Acids; Cholic Acid

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Liver Diseases; Digestive System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; Demyelinating Diseases; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases; Bile Duct Diseases; Biliary Tract Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

CAC-91-10-10 includes data from patients enrolled from 1992-2009. The study end date was arbitrarily chosen as data cut-off point; the disease requires life-long treatment, no final study visit was done. Many patients continued onto study CAC-002-01

Results Point of Contact

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

medinfo@retrophin.com

+1 8776595

Study Officials

• James Heubi, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

• Kenneth Setchell, PhD

  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: December 6, 2000
• First Posted: December 7, 2000
• Study Start: January 1, 1992
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: October 3, 2023
• Results First Posted: July 15, 2020

Record last verified: 2023-09

Locations

US (1)