E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of venous thromboembolism |
Prevenção de tromboembolismo venoso |
|
E.1.1.1 | Medical condition in easily understood language |
Prevention of blood clot in the veins |
Prevenção de um coágulo sanguíneo nas veias |
|
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)
|
Avaliar a segurança e a eficácia de doses diferentes de BAY 1213790 em comparação com as de enoxaparina em doentes submetidos a artroplastia eletiva primária total do joelho (ATJ)
|
|
E.2.2 | Secondary objectives of the trial |
To compare the safety and efficacy of BAY 1213790 with those of apixaban
|
Comparar a segurança e a eficácia de BAY 1213790 com as do apixabano |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients aged ≥18 years undergoing elective primary, unilateral TKA
• Women of non-childbearing potential |
Doentes com idade ≥18 anos submetidos a ATJ eletiva primária unilateral Mulheres que não possam engravidar |
|
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)
|
Risco elevado de hemorragia clinicamente significativa ou alguma das seguintes condições:
o Anemia (Hb <10 g/dl em mulheres, <11 g/dl em homens) na Triagem
o Contagem plaquetária na Triagem <150 x 109/l ou antecedentes de trombocitopenia induzida pela heparina
o TPPa ou TP (INR ou Quick) > LSN na Triagem
o Doença hepática associada a: coagulopatia com risco de hemorragia clinicamente relevante, ou alanina aminotransferase (ALT) > 3x o limite superior da normalidade (LSN) ou bilirrubina total (BT) > 2x LSN com bilirrubina direta > 20% do total na Triagem
o Cirurgia cerebral, espinal ou oftalmológica (exceto cirurgia de catarata) 3 meses antes da aleatorização
o Doenças hemorrágicas conhecidas · Trombose venosa profunda anterior
· Depuração da creatinina abaixo de 60 ml/min, calculada pela fórmula MDRD na Triagem
Cancro ativo, exceto carcinoma basocelular ou espinocelular ou carcinoma in situ do colo do útero que foi clinicamente tratado
Necessidade de terapêutica antiplaquetária dupla ou anticoagulante de dosagem máxima (é permitida uma dose baixa de ácido acetilsalicílico)
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Incidence of composite endpoint consisting of asymptomatic DVT; detected by mandatory bilateral venography; objectively confirmed symptomatic DVT, non-fatal PE, fatal PE, unexplained death for which PE cannot be excluded up to visit 7 (Day 12+3)
• Incidence of composite of major and clinically relevant non-major bleeding up to Visit 7 (Day 12+3) |
•incidência do objectivo composto por trombose venosa profunda (TVP) assintomática, detetada por venografia bilateral obrigatória, TVP sintomática objetivamente confirmada, embolia pulmonar (EP) não fatal, embolia pulmonar (EP) fatal e morte inexplicada para a qual a EP não pode ser excluída até à visita 7 ( Dia 12+3)
•incidência do objetivo composto por hemorragia major e hemorragia não major clinicamente relevante até a visita 7 ( Dia 12+3) |
|
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 composite endpoint of symptomatic DVT or non-fatal PE,
fatal PE, unexplained death for which PE cannot be excluded up to Visit 10 (Day 150±7), objectively confirmed asymptomatic DVT up to Visit 7 (Day 12+3)
• incidence of composite of major and clinically relevant non-major bleeding up to Visit 10 (Day 150±7) |
• incidência do objectivo composto por TVP sintomática ou EP não fatal, EP fatal e morte inexplicada para a qual a EP não pode ser
excluída até à Visita 10 (Dia 150 +/-7), TVP assintomática
objetivamente confirmada até à Visita 7 (Dia 12+3)
•incidência do objectivo composto por hemorragia major e hemorragia não major clinicamente relevante até a visita 10 ( Dia 150+/-7) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Visit 10, Day 150±7 |
Visita 10, Dia 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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 44 |
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 |
Israel |
Latvia |
Lithuania |
Poland |
Portugal |
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 |
Última Visita do Último Participante |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 4 |
E.8.9.2 | In all countries concerned by the trial months | 21 |