E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-alcoholic steatohepatitis (NASH) |
esteatohepatitis no alcohólica (EHNA) |
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E.1.1.1 | Medical condition in easily understood language |
Non-alcoholic steatohepatitis |
esteatohepatitis no alcohólica (EHNA) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10053219 |
E.1.2 | Term | Non-alcoholic steatohepatitis |
E.1.2 | System Organ Class | 10019805 - Hepatobiliary disorders |
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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 evaluate the efficacy of norursodeoxycholic acid (norUDCA) 1500 mg vs. norUDCA 1000 mg vs. placebo for the treatment of NASH |
Evaluar la eficacia del ácido norursodesoxicólico (norUDCA) 1500 mg frente a norUDCA 1000 mg frente a placebo para el tratamiento de EHNA |
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E.2.2 | Secondary objectives of the trial |
To study safety and tolerability (adverse events [AEs], laboratory parameters) of norUDCA |
Estudiar la seguridad y tolerabilidad (acontecimientos adversos [AA], parámetros de laboratorio) del norUDCA |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Must be willing to participate in the study and provide written informed consent • Male or female patients ≥ 18 and < 75 years • Centrally assessed histological evidence of NASH and liver fibrosis • Alanine aminotransferase (ALT) > 0.8 upper limit of normal (ULN) • Women of childbearing potential agree to use a highly effective method of birth control during the entire duration of the trial and for 4 weeks following the last dose of trial treatment |
• Debe estar dispuesto a participar en el estudio y proporcionar un consentimiento informado por escrito • Pacientes masculinos o femeninos ≥ 18 y <75 años. • Pruebas histológicas evaluadas centralmente de EHNA y fibrosis hepática • Alanina aminotransferasa (ALT) > 0,8 límite superior de la normalidad (LSN) • Las mujeres en edad fértil acuerdan utilizar un método anticonceptivo altamente eficaz durante toda la duración del ensayo y durante las 4 semanas posteriores a la última dosis del tratamiento del ensayo. |
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E.4 | Principal exclusion criteria |
• Patients taking prohibited medications • Presence of liver cirrhosis • Type 1 diabetes or uncontrolled Type 2 diabetes • History or presence of any other significant concomitant liver diseases • History of liver transplantation • BMI >45 kg/m^2 • Any known relevant infectious disease (e.g., active tuberculosis, acquired immunodeficiency syndrome [AIDS]-defining diseases) • Abnormal renal function (glomerular filtration rate estimated from cystatin C < 30 ml/min) at screening visit • Any active malignant disease (except for basal cell carcinoma) • Existing or intended pregnancy or breast-feeding |
• Pacientes que toman medicamentos prohibidos. • Presencia de cirrosis hepática. • Diabetes tipo 1 o diabetes tipo 2 no controlada • Historial o presencia de cualquier otra enfermedad hepática concomitante significativa. • Pacientes que se han sometido a trasplante hepático,. • IMC> 45 kg / m ^ 2 • Cualquier enfermedad infecciosa relevante conocida (p. Ej., Tuberculosis activa, síndrome de inmunodeficiencia adquirida [SIDA] que define enfermedades) • Función renal anormal (tasa estimada de filtración glomerular de cistatina C <30 ml / min) en la visita de cribado, • Cualquier enfermedad maligna activa (excepto el carcinoma de células basales)) • Embarazo o lactancia existente o previsto |
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E.5 End points |
E.5.1 | Primary end point(s) |
Resolution of NASH, assessed by centrally scored liver histology, and no worsening of fibrosis from baseline to EOT/withdrawal visit AND/OR Improvement of fibrosis, and no worsening of NAS from baseline to EOT/withdrawal visit |
-Resolución de EHNA, evaluada mediante histología hepática de manera centralizada y sin empeoramiento de la fibrosis desde el periodo basal hasta la visita de fin de tratamiento y/o Mejora de la fibrosis, sin empeoramiento de EHNA desde el periodo basal hasta la visita de fin de tratamiento |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
week 72/withdrawal visit |
semana 72 ( (visita de fin de tratamiento) / visita de retiro |
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E.5.2 | Secondary end point(s) |
• Improvement of NASH and no worsening of fibrosis from baseline to EOT/withdrawal • Change in NAS from baseline to EOT/withdrawal visit • ALT ≤ 0.8 ULN at EOT/withdrawal visit |
-Mejora de la EHNA, sin empeoramiento de la fibrosis, desde el periodo basal hasta la visita de fin de tratamiento/retirada Cambio en NAS desde el periodo basal hasta la visita de fin de tratamiento/retirada -ALT ≤ 0,8 ULN en la visita de fin de tratamiento/retirada |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
week 72 (EOT)/withdrawal visit |
semana 72 ( (visita de fin de tratamiento) / visita de retiro |
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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 | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Dos dosis diferentes de PEI (1500 mg / die o 1000 mg / die norUDCA) |
Two different doses of IMP (1500 mg/d or 1000 mg/d norUDCA) |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 90 |
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
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LVLS |
último sujeto última visita |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |