E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Anaemia of Chronic Kidney Disease |
Anemia de la Nefropatía crónica |
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E.1.1.1 | Medical condition in easily understood language |
A decrease in the number of red blood cells as a result of chronic kidney disease |
Descenso en el número de glóbulos rojos, como resultado de Nefropatía crónica |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058123 |
E.1.2 | Term | Renal anaemia |
E.1.2 | System Organ Class | 100000004851 |
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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 for up to 16 weeks of fixed dose treatment with BAY 85-3934 versus placebo as measured by haemoglobin (Hb) levels. |
Evaluar la eficacia durante 16 semanas del tratamiento en dosis fijas con BAY 85-3934 en comparación con placebo, valorada mediante las concentraciones de hemoglobina (Hb). |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of BAY 85-3934 when administered as a fixed dose for up to 16 weeks versus placebo.
To evaluate the pharmacodynamics (PD) of BAY 85-3934 when administered as a fixed dose for up to 16 weeks.
To evaluate the pharmacokinetics (PK) of BAY 85-3934 and optionally, its metabolite M-1, when administered as a fixed dose for up to 16 weeks.
To investigate selected parameters of kidney function and chronic kidney disease (CKD) progression as well as parameters of iron metabolism and patient reported outcomes (PRO). |
Evaluar la seguridad y tolerabilidad de BAY 85-3934 cuando se administra en dosis fijas durante 16 semanas en comparación con placebo.
Evaluar la farmacodinamia (FD) de BAY 85-3934 cuando se administra en dosis fijas durante 16 semanas.
Evaluar la farmacocinética (FC) de BAY 85-3934 y, opcionalmente, de su metabolito M-1, cuando se administra en dosis fijas durante 16 semanas.
Investigar parámetros seleccionados de la función renal y de la progresión de la nefropatía crónica (NC), así como los parámetros del metabolismo del hierro y los resultados comunicados por el paciente (RCP). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Men who agree to use adequate contraception when sexually active or women without childbearing potential
- Male or female subjects >= 18 years of age with anemia of CKD at screening
- Estimated glomerular filtration rate of < 60 mL/min/1.73 m2 (Modification of Diet in Renal Disease [MDRD] or the formula according to Matsuo, et al)
- Not on dialysis and not expected to begin dialysis during the treatment period of the study (at least 16 weeks from randomization)
- Not treated with any ESA within 8 weeks before randomization
- Mean screening Hb concentration < 10.0 g/dL
- Body weight of 45 kg to 125 kg, inclusive, at screening |
-Hombres que aceptan utilizar un método anticonceptivo adecuado si son sexualmente activos o mujeres que no pueden quedar embarazadas
-Pacientes de ambos sexos de 18 años o más de edad con anemia por NC en el momento de la selección
-Filtración glomerular calculada (FGc) menor de 60 ml/min/1,73 m2 (fórmula de Modification of Diet in Renal Disease o de Matsuo y cols)
-No reciben diálisis y no se espera que comiencen la diálisis durante el período de tratamiento del estudio (al menos 16 semanas desde la aleatorización)
- No reciben tratamiento con fármacos estimuladores de la eritropoyesis (ESA) en las 8 semanas anteriores a la aleatorización
- Concentración media de Hb en la selección menor de 10,0 g/dl
- Peso corporal entre 45 kg y 125 kg, ambos inclusive, en la selección |
|
E.4 | Principal exclusion criteria |
- Subjects with significant acute or chronic bleeding, such as overt gastrointestinal bleeding
- Chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in remission
- Previous or concurrent cancer except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis, and T1) or any cancer curatively treated > 3 years prior to randomization
- Subjects treated with any ESA within the 8 weeks before randomization
- Red blood cell (RBC) containing transfusion within the 8 weeks before randomization
- History of cardio- (cerebro-) vascular events (e.g., unstable angina, myocardial infarction, stroke, transient ischemic attack, deep vein thrombosis, pulmonary embolism) within the last 6 months from initial screening visit
- Severe rhythm or conduction disorders (e.g., HR < 50 or > 110 bpm, atrial fibrillation or flutter, prolonged QT > 500 msec, second or third degree atrioventricular [AV] block)
- New York Heart Association Class III or IV congestive heart failure
- Severe hepatic insufficiency (defined as alanine aminotransferase [ALT], aspartate aminotransferase [AST], or gamma glutamyl transferase [GGT] > 3 x the upper limit of normal [ULN], total bilirubin > 2 mg/dL, or Child-Pugh B and C) or active hepatitis, in the investigator's opinion |
-Pacientes con hemorragia aguda o crónica significativa, por ejemplo, una hemorragia digestiva franca
-Enfermedad inflamatoria crónica que pueda afectar a la eritropoyesis (como el lupus eritematoso sistémico, la artritis reumatoide o la enfermedad celíaca) aunque se encuentre en remisión en la actualidad
- Cáncer anterior o concurrente, excepto carcinoma cervical in situ, carcinoma basocelular tratado, tumores vesicales superficiales (Ta, Tis y T1) o cualquier cáncer que haya recibido tratamiento curativo más de 3 años antes de la aleatorización
- Pacientes tratados con algún ESA en las 8 semanas anteriores a la aleatorización
-Transfusiones de eritrocitos en las 8 semanas anteriores a la aleatorización
-Antecedentes de episodios cardio- (cerebro-) vasculares (como angina inestable, infarto de miocardio, ictus, ataque isquémico transitorio, trombosis venosa profunda y embolia pulmonar) en los 6 meses anteriores a la visita de selección inicial.
-Trastornos graves del ritmo o la conducción (como FC inferior a 50 o mayor de 110 lpm, fibrilación o aleteo auriculares, QT prolongado más de 500 ms, bloqueo auriculoventricular [AV] de segundo o tercer grado)
- Insuficiencia cardíaca congestiva de las clases III o IV de la New York Heart Association (NYHA) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1) Change in local laboratory haemoglobin level from baseline to the average during the last 4 weeks treatment period |
1) Variación de la concentración de Hb medida en el laboratorio local entre el momento inicial y las últimas 4 semanas del período de tratamiento |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) Baseline and week 12 to 16 |
1) Inicio y semanas 12 a 16 |
|
E.5.2 | Secondary end point(s) |
1) Change in local laboratory haemoglobin level from baseline
2) Speed of change in haemoglobin level per unit time
3) Treatment exposure (Duration)
4) Number of participants with serious adverse events as a measure of safety and tolerability
5) Pharmacodynamics characterized by erythropoietin concentration
6) Pharmacodynamics characterized by reticulocyte count |
1) Variación en la concentración de Hb medida en el laboratorio local entre el momento inicial
2) Velocidad de la variación en la concentración de Hb en unidad de tiempo
3) Exposición al tratamiento del estudio ( Duración)
4) Número de participantes con Acontecimientos adversos graves, como medida de seguridad y tolerabilidad.
5) Pharmacodinámica caracterizada por concentración de eritropoetina.
6) Pharmacodinámica caracterizada por recuento de reticulocitos |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Baseline up to 12 weeks
2) Up to 16 weeks
3) Up to 16 weeks
4) Up to 16 weeks
5) Several time points up to 16 weeks
6) Several time points up to 16 weeks |
1) Inicial hasta 12 semanas
2) Hasta 16 semanas
3) Hasta 16 semanas
4) Hasta 16 semanas
5) En diferentes momentos hasta 16 semanas
6) En diferentes momentos hasta 16 semanas |
|
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 | 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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability |
Tolerabilidad |
|
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 6 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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 |
Australia |
Bulgaria |
Germany |
Hungary |
Italy |
Japan |
Romania |
Korea, Republic of |
Spain |
United Kingdom |
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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
|
Last subject last visit |
Última visita del último paciente |
|
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 | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 2 |