E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients wih Cholestatic Pruritus |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic liver disease with impaired bile flow (cholestasis) causing a severe itch. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•Assess the safety and tolerability of A4250, orally administered
•Explore changes in serum total bile acids |
|
E.2.2 | Secondary objectives of the trial |
•Assessment of the safety and tolerability of A4250
•Demonstrate the efficacy of A4250, orally administered during a four week treatment period, on liver biochemistry variables and on pruritus parameters |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Diagnosis of pruritus due to chronic cholestasis based on history and investigator judgment
- This will include but will not be restricted to patients with Progressive familial intrahepatic cholestasis (PFIC), Alagille syndrome (ALGS), Biliary Atresia and Sclerosing Cholangitis
•Laboratory markers of cholestasis identified within 3 months before Visit 1
|
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E.4 | Principal exclusion criteria |
•Any condition that in the opinion of the investigator constitutes a risk for the patient or a contraindication for participation and completion of the study, or could interfere with study objectives, conduct, or evaluations
•Clinical or biochemical signs of decompensated liver disease
•Liver transplantation
•Other reason for pruritus than chronic cholestasis such as treatment refractory atopic dermatitis, other primary skin diseases etc.
•Treatment with bile acid sequestrants (cholestyramine, colesevelam, colestipol or similar) during the screening period
|
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is change in total serum bile acids.
The primary safety endpoint will be the occurrence of treatment-emergent SAEs during the four treatment weeks. Description and severity of any SAE will also be reported. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The end of the four week treatment. |
|
E.5.2 | Secondary end point(s) |
•VAS-itch
•Whitington itching score
•PK
•Liver biochemistry evaluation
•Occurrence of TEAEs during the whole study period. Description and severity of any AE will also be reported. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The end of four week treatment. |
|
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
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 | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
Date of the final clinical database lock. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |