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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.
Sponsor:
Information provided by (Responsible Party):
Asklepion Pharmaceuticals, LLC
ClinicalTrials.gov Identifier:
NCT01115582
First received: January 19, 2010
Last updated: September 15, 2011
Last verified: September 2011
History of Changes
  Purpose

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.


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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Bio-equivalence Study
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

Further study details as provided by Asklepion Pharmaceuticals, LLC:

Primary Outcome Measures:
  • Evaluation of efficacy of manufactured cholic acid capsules compared to the currently used cholic acid capsules prepared in the pharmacy. [ Time Frame: Measured at beginning of study at Day 1 (Visit 1) which is when the first dose ofTBM Cholic Acid is administered, and one month after Day 1 at Day 30 (+/- 3) days which is the final study visit. ] [ Designated as safety issue: No ]
    This will be done by assessing (1) serum transaminases and (2) suppression of synthesis of atypical bile acids.


Secondary Outcome Measures:
  • Number and Severity of Adverse Events as a Measure of Safety & Tolerability [ Time Frame: Measured at beginning of study at Day 1(Visit 1) when the first dose ofTBM Cholic Acid is administered, two weeks after Visit 1, Day 1 via a telephone visit (Day 14 +/- 3 days), & one month after Day 1 at Day 30 (+/- 3) days at the final study visit. ] [ Designated as safety issue: Yes ]
    Safety & Tolerabilty of TBM Cholic Acid will be assessed by number and severity of adverse events, vital signs, physical examination findings, and clinical laboratory results.


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
Active Comparator: 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.
Cholic Acid Capsules
Currently Used Pharmacy Manufactured Cholic Acid Capsules (CCHMC)
 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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01115582

Locations
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Asklepion Pharmaceuticals, LLC
Investigators
Principal Investigator: James E Heubi, MD Children's Hospital Medical Center, Cincinnati
  More Information

Publications:

Responsible Party: Asklepion Pharmaceuticals, LLC
ClinicalTrials.gov Identifier: NCT01115582     History of Changes
Other Study ID Numbers: CAC-001-01
Study First Received: January 19, 2010
Last Updated: September 15, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Asklepion Pharmaceuticals, LLC:
Inborn Errors
Bile Acid
Pediatrics
Liver Disease

Additional relevant MeSH terms:
Bile Acids and Salts
Cholic Acids
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 22, 2013