E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Up to 67% of PBC patients have an incomplete biochemical response to UDCA and remain at increased risk for progression to cirrhosis and liver-related death. In this study we will prospectively examine the therapeutic effects of bezafibrate (a pan-agonist activating PPARalpha/delta/gamma) in patients with early-stage PBC with a specific focus on improvement of liver functions, inflammation, lipid profile, oxidative status and endothelial function. |
Bis zu zwei Drittel der PBC PatientInnen sprechen nicht ausreichend auf UDCA an und weisen ein erhöhtes Risiko für eine Progression zur Leberzirrhose und dadurch bedingten Tod auf. In dieser prospektiven Studie sollen die therapeutischen Effekte von Bezafibrat (ein Panagonist, der PPARalpha/delta/gamma aktiviert) bei PatientInnen mit PBC im Frühstadium in Hinblick auf Verbesserung der Leberfunktion, Inflammation, Lipidprofil, oxidativer Status und Endothelfunktion untersucht werden. |
|
E.1.1.1 | Medical condition in easily understood language |
Up to 67% of PBC patients have an incomplete biochemical response to UDCA. Effects of bezafibrate will be examined with a specific focus on improvement of laboratory parameters and vascular function. |
Bis zu 2/3 der PBC PatientInnen sprechen nicht ausreichend auf UDCA an. Es sollen daher die Effekte von Bezafibrat in Hinblick auf Laborparameter und Gefäßfunktion untersucht werden. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
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 |
Our major hypothesis is that the treatment with bezafibrate will improve levels of AP in early-stage PBC patients with an incomplete biochemical response to UCDA through a combination of metabolic and anti-inflammatory effects. |
Unsere Hypothese ist, dass die Therapie mit Bezafibrat die AP bei PBC PatientInnen im Frühstadium und unzureichendem Ansprechen auf UCDA aufgrund metabolischer und anti-inflammatorischer Effekte vebessert. |
|
E.2.2 | Secondary objectives of the trial |
Moreover, we will focus on mechanistic effects on markers of liver function, chronic low-grade inflammation, dyslipidemia, oxidative stress and endothelial function. |
Desweiteren werden wir die mechanistischen Effekte in Bezug auf Leberfunktion, chronische niedriggradige Inflammation, Dyslipidämie, oxidativer Stress und Endothelfunktion untersuchen. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Incomplete responders to standard UDCA therapy (AP > 1.5x ULN after one year)
PBC stage I – II (biopsy proven and/or positive AMA)
Male or female gender
Age 18 – 70 years
Normal kidney function
Signed informed consent |
inkomplette Responder auf Standard UDCA Therapie (AP >1.5x ULN nach 1 Jahr)
PBC Stadium I-II (entsprechende Leberhistologie und/oder AMA positiv)
männliches oder weibliches Geschlecht
Alter 18-70 Jahre
normale Nierenfunktion
schriftliche Einwilligung der PatientInnen |
|
E.4 | Principal exclusion criteria |
PBC stage III – IV
Age > 70 years
Decompensated liver disease (Child-Pugh class B/C, presence of ascites, esophageal varices)
Cholelithiasis
ALT or AST > 3x ULN
CK > 5x ULN or CK >3x ULN with muscle pain, tenderness or weakness
Pregnancy or breastfeeding
Premenopausal women without certain contraception
Known hypersensitivity to fibrates
Current treatment with lipid-lowering drugs, immunosuppressants, coumarin-based anticoagulants, monoamine oxidase inhibitors
|
PBC Stadium III-IV
Alter >70 Jahre
dekompensierte Lebererkrankung (Child-Pugh B/C, Ascites, Oesophagusvarizen)
Cholelithiasis
ALT oder AST >3x ULN
CK >5x ULN oder CK >3x ULN mit Muskelschmerzen oder Muskelschwäche
Schwangerschaft oder Stillen
prämenopausale Frauen ohne sichere Kontrazeption
bekannte Hypersensitivität gegenüber Fibraten
laufende Behandlung mit lipidsenkenden Medikamenten, Immunsuppressiva, Antikoagulantien vom Cumarintyp, Monoaminooxidase-Hemmer |
|
E.5 End points |
E.5.1 | Primary end point(s) |
alkaline phosphatase (AP) |
alkalische Phosphatase (AP) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Screening (within 4 weeks prior to baseline visit), at weeks 0 (baseline), 4, 8 |
Screening (innerhalb 4 Wochen vor Baseline Visite), Woche 0 (Baseline), Woche 4, Woche 8 |
|
E.5.2 | Secondary end point(s) |
Liver enzymes
Composition and concentrations of VLDL, IDL, LDL and HDL particles
Cholesterol precursors and metabolites
Markers of inflammation and oxidative stress
Vascular morphology and function |
Leberenzyme
Zusammensetzung and Konzentration von VLDL, IDL, LDL und HDL Partikeln
Cholesterinvorläufer und Metabolite
Marker für Inflammation und oxidativen Stress
Gefäßmorphologie und -funktion |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Liver enzymes at screening, at weeks 0, 4, 8
Composition and concentrations of VLDL, IDL, LDL and HDL particles at weeks 0, 4, 8
Cholesterol precursors and metabolites at weeks 0, 4, 8
Markers of inflammation and oxidative stress at weeks 0, 4, 8
Vascular morphology and function at weeks 0, 8 |
Leberenzyme: Screening, Woche 0, 4, 8
Zusammensetzung and Konzentration von VLDL, IDL, LDL and HDL Partikeln: Woche 0, 4, 8
Cholesterinvorläufer und Metabolite: Woche 0, 4, 8
Marker für Inflammation und oxidativen Stress: Woche 0, 4, 8
Gefäßmorphologie und -funktion: Woche 0, 4, 8 |
|
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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | No |
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
|
End of the trial = last patient out |
Ende der Studie = letzte(r) PatientIn abgeschlossen |
|
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 | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |