E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of venous thromboembolism |
Prevención del tromboembolismo venoso |
|
E.1.1.1 | Medical condition in easily understood language |
Prevention of blood clot in the veins |
Prevención de la coagulación de la sangre en las venas |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049909 |
E.1.2 | Term | Venous thromboembolism prophylaxis |
E.1.2 | System Organ Class | 100000004865 |
|
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 assess the safety and efficacy of different doses of BAY 1213790 in comparison with those of enoxaparin in patients undergoing elective, primary, unilateral total knee arthroplasty (TKA) |
Evaluar la seguridad y la eficacia de diferentes dosis de BAY 1213790 en comparación con las dosis de enoxaparina en pacientes sometidos a una artroplastia total programada, primaria y unilateral de rodilla (ATR). |
|
E.2.2 | Secondary objectives of the trial |
To compare the safety and efficacy of BAY 1213790 with those of apixaban |
Comparar la seguridad y la eficacia de BAY 1213790 con apixaban |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients aged >= 8 years undergoing elective primary, unilateral TKA • Women of non-childbearing potential |
- Pacientes >= 18 años sometidos a una ATR programada primaria y unilateral - Mujeres sin capacidad reproductora |
|
E.4 | Principal exclusion criteria |
• High risk for clinically significant bleeding or any of the following conditions: o Anemia (Hb <10 g/dL in women, < 11 g/dL in men) at Screening o Platelet count at Screening < 150 x 109/L or history of heparin-induced thrombocytopenia o aPTT or PT (INR or Quick) > ULN at Screening o Hepatic disease associated with either: coagulopathy leading to a clinically relevant bleeding risk, or alanine aminotransferase (ALT) > 3x upper level of normal (ULN) or total bilirubin (TB) > 2x ULN with direct bilirubin > 20% of the total at Screening o Brain, spinal, or ophthalmologic surgery (except cataract surgery) within 3 months prior to randomization o Known bleeding disorders • Prior deep vein thrombosis • Creatinine clearance below 60 ml/min, calculated by MDRD formula at Screening • Active cancer except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been curatively treated • Contraindication listed in the local label of the comparator treatments • Requirement for full dose anticoagulation or dual antiplatelet therapy (low dose of acetylsalicylic acid is allowed) |
• Riesgo elevado de hemorragia clínicamente significativa o cualquiera de las patologías siguientes: o Anemia (Hb < 10 g/dl en mujeres, < 11 g/dl en hombres) en el momento de la selección o Cifra de plaquetas en el momento de la selección < 150 x 109/l o antecedentes de trombocitopenia inducida por heparina o TTPa o TP (INR o Quick) > Límite superior de normalidad (LSN) en el momento de la selección o Hepatopatía asociada a: coagulopatía que conlleva riesgo de hemorragia clínicamente relevante, o alanina-aminotransferasa (ALT) > 3 veces el (LSN o bilirrubina total (BT) > 2 veces el LSN con bilirrubina directa > 20 % del total en la selección o Cirugía cerebral, de columna u oftalmológica (excepto cirugía de cataratas) en los 3 meses anteriores a la aleatorización o Trastornos hemorrágicos conocidos • Trombosis venosa profunda previa • Aclaramiento de creatinina inferior a 60 ml/min, calculado según la fórmula MDRD en la selección • Cáncer activo excepto carcinoma de piel de células basales o escamosas o carcinoma in situ del cuello uterino para el que se haya recibido tratamiento curativo • Contraindicaciones que se incluyen en la ficha técnica local de los tratamientos comparadores • Necesidad de tratamiento anticoagulante con dosis completas o doble antiagregación (se permiten dosis bajas de ácido acetilsalicílico) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Incidence of asymptomatic DVT, detected by mandatory bilateral venography, and objectively confirmed symptomatic DVT or non-fatal PE (symptomatic VTE), fatal PE and unexplained death for which PE cannot be excluded
• Incidence of major and clinically relevant non-major bleeding |
• Incidencia de TVP asintomática, detectada por flebografía bilateral obligatoria, y TVP sintomática confirmada objetivamente, o EP no mortal, EP mortal y muerte sin causa aparente para la cual no se puede excluir la EP
• Hemorragias graves y no graves clínicamente relevantes |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Visit 7, Day 12+3 |
Visita 7, dia 12+3 |
|
E.5.2 | Secondary end point(s) |
• Incidence of symptomatic DVT or non-fatal PE (symptomatic VTE), fatal PE and unexplained death for which PE cannot be excluded up to Visit 10 (Day 150±7) or objectively confirmed asymptomatic DVT up to Visit 7 (Day 12+3)
• Incidence of major and clinically relevant non-major bleeding |
• Incidencia de TVP sintomática o EP no mortal (TVP sintomática), EP mortal y muerte sin causa aparente para la cual no se puede excluir la EP hasta la Visita 10 (día 150±7) o TVP asintomática confirmada objetivamente hasta la Visita 7 (día 12+3)
• Hemorragias graves y no graves clínicamente relevantes |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Visit 10, Day 150±7 |
Visita 10, Día 150±7 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
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 | 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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
abierto para el tratamiento y ciego para el observador para las dosis de BAY1213790 |
open-label for the assignment to the study drugs, observer blinded to the dose of BAY1213790 |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Canada |
Czech Republic |
Germany |
Greece |
Hungary |
Israel |
Latvia |
Lithuania |
Poland |
Russian Federation |
South Africa |
Spain |
Ukraine |
|
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
|
LVLS |
Último sujeto última visita |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 21 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 21 |
E.8.9.2 | In all countries concerned by the trial days | 0 |