E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
adult patients (18-70 years old) who have been treated with azathioprine, 6-mercaptopure or 6-thioguanine for inflammatory bowel disease, in whom hepatotoxicity occured as an adverse event, are eligible. Prior to definite inclusion, the patients will be screened to make other causes of hepatotoxicity less likely. |
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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 |
To study the influence of acetylcysteine co-administartion on thiopurine induced hepatotoxicity. |
|
E.2.2 | Secondary objectives of the trial |
- To study the influence of acetylcysteine co-administration on markers for oxidative stress - To study the influence of acetylcysteine co-administration on thiopurine metabolism |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
written informed consent; adult patients, aged between 18 and 70 years; Crohn's disease or ulcerative colitis; azathioprine, 6-mercaptopurine or 6-thioguanine therapy, Grade 1 or 2 on the CTCAE v3.0 of at least one of the following liver tests: aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), alkaline phosphatase (AP), gamma-glutamyl transferase (GGT) or total bilirubine (Bili). |
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E.4 | Principal exclusion criteria |
Serological findings consistent with active viral hepatitis A, B, C EBV or CMV; findings suggesting auto-immune hepatitis (AIH); cholestasis; known liver diseases inlcuding: Hepatitis A, B or C, cirrhosis, AIH, primary sclerosing cholangitis, primary biliairy cirrhosis, hepatocellular carcinoma, metastatic liver disease or symptomatic cholecystolithiasis; Use of methotrexate or other chemotherapy within the last three months; use of N-acetylcysteine during thioipurine therapy; allergy to N-acetylcysteine; lactation; pregnancy; 6-TGN level >1200 pmol |
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E.5 End points |
E.5.1 | Primary end point(s) |
Changes in liver tests ASAT, ALAT, GGT, AF and Bili. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
E.8.1.6 | Cross over | Yes |
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 | Information not present in EudraCT |
E.8.2.3.1 | Comparator description |
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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 | No |
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 | Information not present in EudraCT |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |