E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Reduction of cardiovascular risk may become key for the management of PBC. Therefore information on safety and efficacy (lipid-lowering effects) of statins in chronic cholestatic disorders is essential. Moreover, the study will answer the open question whether long-term treatment with statins may have potential beneficial effects on the course of PBC. |
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MedDRA Classification |
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 |
Primary biliary cirrhosis (PBC) is often associated with abnormalities in serum lipids. Hypercholesterolemia is an established risk factor for cardiovascular morbidity and mortality. Since many PBC patients have a very slow progression of their underlying liver disease cardiovascular risk factors may become more relevant as prognostic factors. Statins may reduce serum cholesterol levels and cardiovascular risk in PBC patients although this remains to be determined. Statins are generally well tolerated by patients with nonalcoholic fatty liver disease (NAFLD) and are not associated with an increased risk of hepatotoxicity. In regard to cholestatic liver diseases only limited data on safety of statins are available. Atorvastatin did not statistically increase liver enzymes in PBC patients in a recent pilot study at the Medical University Graz. However, data on long-term treatment with atorvastatin in these patients are not yet available. |
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E.2.2 | Secondary objectives of the trial |
Moreover, we aim to test the hypotheses that the cholesterol-lowering effect of atorvastatin and the safety concerning hepatotoxicity in PBC patients does not differ from non-cholestatic, hypercholesterolemic patients. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Inclusion criteria (PBC): LDL-cholesterol >= 130 mg/dl Primary biliary cirrhosis (AMA positive or biopsy proven) Male or female gender Age 18-70 years Normal kidney function
Inclusion criteria (non-PBC): LDL-cholesterol >= 130 mg/dl matched for age, gender, glucose metabolism and vascular disease manifestations |
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E.4 | Principal exclusion criteria |
Primary biliary cirrhosis Stage III-IV (Ludwig Score) Liver cirrhosis Decompensated liver disease ( > Child-Pugh class B, ascites, esophageal varices) ALT or AST > 2x ULN Pregnancy or breastfeeding Premenopausal women without certain contraception Known hypersensitivity to HMG-CoA reductase inhibitors
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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 | No |
E.8.1.3 | Single blind | Yes |
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 | Yes |
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 | 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 | Information not present in EudraCT |
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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End of the trial = last patient out |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 30 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 30 |