E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
diabetic kidney disease |
nefropatía diabética |
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E.1.1.1 | Medical condition in easily understood language |
diabetic kidney disease |
nefropatía diabética |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061835 |
E.1.2 | Term | Diabetic nephropathy |
E.1.2 | System Organ Class | 10038359 - Renal and urinary 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 |
The main objectives of the trial are to demonstrate the effectiveness of BI 685509 and to characterize the dose-response relationship for BI 685509 in patients with DKD by assessing 3 doses and placebo. |
Los objetivos principales del ensayo son mostrar la eficacia de BI 685509 y caracterizar la relación dosis-respuesta para BI 685509 en pacientes con ND mediante la evaluación de 3 dosis y placebo. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial. 2. Male or female patients aged ≥ 18 years at time of consent. 3. eGFR (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula) ≥ 20 and < 90 mL/min/1.73 m2 at Visit 1 by central laboratory analysis. 4. UACR ≥ 200 and < 3,500 mg/g in spot urine (midstream urine sample) by central laboratory analysis at Visit 1. 5. Treatment with the highest tolerated dose of either ACEi or ARB (but not both together), and stable dose for ≥ 4 weeks before Visit 1 with no planned change of the therapy during the trial. 6. Stable on anti-hypertensives, NSAIDs, endothelin receptor antagonists, systemic steroids, within at least 4 weeks prior to Visit 1 until start of trial treatment, with no planned change of the therapy during the trial. 7. Patients with stable type 1 or type 2 diabetes mellitus, diagnosed before informed consent. Treatment (including SGLT2 inhibitor and/or GLP1 receptor agonist) should have been unchanged or changes deemed minor (according to investigator’s judgement) within 4 weeks before Visit 1 and until start of trial treatment. 8. Glycated Haemoglobin (HbA1c) < 10.0% at Visit 1 measured by the central laboratory. 9. Seated SBP ≥ 110 and ≤ 160 mmHg and DBP ≥ 65 and ≤ 110 mmHg at Visit 1 and optimized anti-hypertensive treatment according to local standard of care and investigator’s judgement. 10. Body Mass Index (BMI) ≥ 18.5 and < 50 kg/m2 at Visit 1. 11. Male patients able to father a child must be willing to use condoms if their sexual partner is a Women of child-bearing potential. Women of child-bearing potential must be ready and able to use highly effective methods of birth control per ICH M3 (R2). Such methods should be used throughout the trial. |
1. Consentimiento informado firmado y con fecha de acuerdo con la ICHGCP y la legislación local previo a la admisión al estudio. 2. Pacientes de ambos sexos ≥ 18 años en el momento del consentimiento. 3. eGFR ≥ 20 y < 90 mL/min/1,73 m2 en la visita 1 mediante el laboratorio central de análisis. 4. UACR ≥ 200 y < 3500 mg/g en muestra de orina (recogida del flujo intermedio) por el laboratorio central de análisis en la visita 1. 5. Tratamiento con la máxima dosis tolerada de iECA o antagonistas del receptor de angiotensina (pero no conjuntamente), y dosis estable por ≥ 4 semanas antes de la visita 1 sin ningún cambio planeado de la terapia durante el ensayo. 6. Estabilizados en antihipertensivos, AINEs, antagonistas del receptor de endotelina, esteroides sistémicos, al menos 4 semanas antes de la visita 1 hasta el inicio del estudio, sin ningún cambio planeado de la terapia durante el ensayo. 7. Pacientes con diabetes de tipo 1 o de tipo 2 estable, diagnosticados antes del momento del consentimiento. El tratamiento (incluyendo inhibidores de SGLT2 y/o agonistas del receptor GLP1) debería mantenerse sin cambios o con cambios de importancia menor (de acuerdo con el criterio del investigador) dentro de las 4 semanas anterior a la visita 1 y hasta el inicio del tratamiento del estudio. 8. Hemoglobina glicada (HbA1c) < 10,0% en la visita 1 medida por el laboratorio central. 9. Tensión arterial sistólica ≥ 110 mmHg y y ≤ 160 mmHg y tensión arterial diastólica ≥ 65 mmHg y ≤ 110 mmHg en la visita 1 y tratamiento antihipertensivo optimizado de acuerdo con el tratamiento estándar y el criterio del investigador. 10. Índice de masa corporal (IMC) ≥ 18,5 y < 50 kg/m2 en la visita 1. 11. Los pacientes varones en edad fértil deben estar dispuestos a usar profiláctico si su compañera sexual es una mujer en edad fértil. Las mujeres en edad fértil deben ser capaces de usar métodos anticonceptivos altamente efectivos descritos en la ICH M3 (R2). Estos métodos deberán usarse durante el estudio. |
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E.4 | Principal exclusion criteria |
1. Treatment with Renin Angiotensin Aldosterone System RAAS interventions (apart from either ACEi or ARB), phosphodiesterase inhibitors, nitrates, sGC-stimulators/activators (other than trial treatment) or any other restricted medication (including OATP1B1/3 inhibitors, UGT inhibitors/inducers) as provided in the Investigator Site File (ISF) within 4 weeks prior to visit 1 and throughout screening and baseline run-in. Patients who must or wish to continue the intake of restricted medications (see section 4.2.2.1) or any drug considered likely to interfere with the safe conduct of the trial are also excluded. 2. Any clinically relevant laboratory value from screening until start of trial treatment, which in the investigator’s judgement puts the patient at additional risk. 3. Biopsy or otherwise confirmed non-diabetic chronic kidney disease, or non-diabetic chronic kidney disease in the opinion of investigator, e.g., Autosomal Dominant Polycystic Kidney Disease (ADPKD), uncontrolled lupus nephritis. The presence of a hypertensive etiology does not need to be excluded unless it is evident this is the only cause for the CKD. 4. Any immunosuppression therapy or immunotherapy in the last 3 months prior to visit 1 and throughout screening and baseline run-in (except prednisolone ≤10 mg or equivalent). 5. Acute kidney injury (AKI) according to the Kidney Disease: Improving Global Outcomes (KDIGO) definition in the 30 days prior to Visit 1 until the start of trial treatment. 6. Planned start of chronic renal replacement therapy during the trial or end stage renal disease before start of trial treatment. 7. Known history of moderate or severe symptomatic orthostatic dysregulation as judged by the investigator before start of trial treatment5. 8. The patient has an active infection with SARS-CoV-2 (or is known to have a positive test) from screening until randomisation. 9. Medical history of cancer or treatment for cancer in the last two years prior to Visit 1 (except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of uterine cervix, and prostatic cancer of low grade [T1 or T2]). 10. Major surgery (investigator’s judgement) planned during the trial. 11. History of clinically relevant allergy/ hypersensitivity that would interfere with trial participation including allergy to investigational product/ placebo or its excipients (e.g. lactose monohydrate – see Investigator Brochure) 12. Any other medical condition6 that in the investigator’s opinion poses a safety risk for the patient or may interfere with the trial objectives. 13. Previous randomisation in this trial. Further criteria apply. |
1. Tratamiento que intervenga en el sistema renina-angiotensinaaldosterona (a parte de iECAs o antagonistas del receptor de angiotensina), inhibidores de fosfodiesterasa, nitratos, estimuladores de sGC (a parte del tratamiento del estudio) u otra medicación restringida (incluyendo inhibidores OATP1B1/3, inductores/inhibidores de UGT) como dicta el archivo local del investigador en las 4 semanas previas a la visita 1 y durante toda la selección. Los pacientes que deban o quieran continuar con la toma de la medicación restringida (ver sección 4.2.2.1) u otra medicación que se considere que puede interferir con la ejecución segura del ensayo serán también excluidos. 2. Cualquier valor de laboratorio clínicamente relevante desde la selección al inicio del tratamiento del estudio, que ponga al paciente en riesgo adicional bajo el criterio del investigador. 3. Nefropatía crónica no diabética confirmada por biopsia u otros métodos, otros tipos de nefropatía crónica no diabética según la opinión del investigador, por ejemplo enfermedad renal poliquística autosómica dominante (ERPAD), lupus nefrítico no controlado. La presencia de hipertensión etiológica no necesariamente es excluyente a menos que sea evidente que es la única causa de la nefropatía diabética. 4. Cualquier terapia de inmunosupresión o inmunoterapia en los 3 meses previos a la visita 1 y durante toda la selección y estudio (excepto prednisolona ≤ 10 mg o equivalentes). 5. Lesión renal aguda de acuerdo con la definición de "Kidney Disease: Improving Global Outcomes (KDIGO)" en los 30 días previos a la visita 1 y hasta el inicio del tratamiento del estudio. 6. Inicio planeado de terapia para trasplante renal durante el estudio o enfermedad renal terminal antes del inicio del tratamiento del estudio. 7. Antecedentes conocidos de desregulación ortostática de moderada a severa a juicio del investigador antes del inicio del estudio. 8. Pacientes con infección activa de SARS-CoV-2 (o test positivo) desde la selección hasta la aleatorización. 9. Antecedentes médicos de cáncer o tratamiento oncológico en los últimos dos años previos a la visita 1 (excepto carcinoma de células basales de la piel, carcinoma de cuello de útero in situ y cáncer prostático de grado bajo [T1 o T2] tratados adecuadamente). 10. Intervenciones quirúrgicas mayores (a juicio del investigador) planeadas durante el estudio. 11. Antecedentes clínicos relevantes de alergia/hipersensibilidad que puedan interferir con la participación en el estudio incluyendo alergia al producto en investigación/placebo o sus excipientes (por ejemplo, lactosa monohidrato - ver manual del investigador). 12. Otras condiciones que en opinión del investigador posean un riesgo para la seguridad del paciente o interfiera con los objetivos del ensayo. Otros criterios aplican. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Change from baseline in log transformed Urine Albumin Creatinine Ratio (UACR) measured in 10-hour urine after 20 weeks of trial treatment. |
1) Cambio desde el valor inicial en el UACR transformado logarítmicamente medido en la primera orina de la mañana después de 20 semanas del tratamiento del ensayo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) 20 weeks |
1) 20 semanas |
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E.5.2 | Secondary end point(s) |
1) Change from baseline in log transformed UACR measured in First Morning Void urine after 20 weeks of trial treatment. 2) Proportion of patients achieving UACR decreases in 10-hour urine of at least 20% from baseline after 20 weeks of trial treatment. 3) Proportion of patients achieving UACR decreases in First Morning Void urine of at least 20% from baseline after 20 weeks of trial treatment. |
1) Cambio desde el valor inicial en el UACR transformado logarítmicamente medido en la primera orina de la mañana después de 20 semanas del tratamiento del ensayo. 2) Proporción de pacientes que logran disminuciones del UACR en orina de 10 horas de al menos un 20% con respecto al valor inicial después de 20 semanas del tratamiento del ensayo. 3) Proporción de pacientes que logran disminuciones del UACR en la primera orina de la mañana de al menos un 20% con respecto al valor inicial después de 20 semanas del tratamiento del ensayo. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) 20 weeks 2) 20 weeks 3) 20 weeks |
1) 20 semanas 2) 20 semanas 3) 20 semanas |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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 |
Argentina |
Australia |
Canada |
China |
Hong Kong |
Japan |
Malaysia |
Mexico |
New Zealand |
United States |
Poland |
Netherlands |
Spain |
Denmark |
Portugal |
United Kingdom |
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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 |
Última visita del último paciente |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 3 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 1 |