E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with inborn errors of bile acid synthesis and metabolism |
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E.1.1.1 | Medical condition in easily understood language |
Patients with birth defects inherited from their parents which means that they cannot make normal bile acids. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10070882 |
E.1.2 | Term | Inborn error in primary bile acid synthesis |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the therapeutic efficacy of TBM cholic acid capsules compared with the effect of the CU formulation of cholic acid prepared in the CCHMC Pharmacy. |
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E.2.2 | Secondary objectives of the trial |
Safety and tolerability monitoring compared with baseline. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•The patient must have stable transaminase levels within 2 times the upper limits of the normal range.
•The patient must have a diagnosis of an inborn error of bile acid synthesis.
•The patient and/or parent/legal guardian must have signed the written informed consent document before study start.
•Assent must be obtained from eligible children greater than age 7 years
•The patient must be currently receiving CU cholic acid therapy under IND 45,470.
• The patient must be willing and able to comply with all study assessments and procedures.
•The patient must be able to make two visits (Visit 1 and Visit 2) to the study site (CCHMC).
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E.4 | Principal exclusion criteria |
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E.5 End points |
E.5.1 | Primary end point(s) |
Therapeutic effect of commercial cholic acid capsules compared with the CCHMC capsules on:
-serum transaminases and
-regulation of the synthesis of atypical bile acids.
Assessment at day 0 and day 30, as measured by urine and serum bile acid analysis using mass spectrometry. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Safety and tolerability of TBM cholic acid capsules
Malabsorption assessment including measurements of vitamin A, E, and D, and prothrombin time |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Adverse event reporting from parents at days 0, 14 (by telephone) and 30.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Yes |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.1.7.1 | Other trial design description |
Cohort study using each patient as their own control |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.3.1 | Comparator description |
Cholic acid capsules, hard manufactured at CCHMC (current clinical formulation) |
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E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial months | 4 |