E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Schizophrenia |
Esquizofrenia |
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E.1.1.1 | Medical condition in easily understood language |
Schizophrenia |
Esquizofrenia |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039626 |
E.1.2 | Term | Schizophrenia |
E.1.2 | System Organ Class | 10037175 - Psychiatric 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 objective of this trial is to collect additional safety data in patients with cognitive impairment due to schizophrenia, who participated in and completed the 26-week treatment period with BI 425809 or matching placebo of one of the phase III clinical trial program for BI 425809 (trial # 1346-0011, 1346-0012, 1346-0013). |
El objetivo de este ensayo es recopilar datos adicionales de seguridad en pacientes con deterioro cognitivo debido a esquizofrenia, que participaron y completaron el tratamiento de 26 semanas o el placebo equivalente de uno de los programas de ensayos clínicos de fase III de BI 425809 (ensayo n.º 1346-0011, 1346-0012, 1346-0013) |
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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 Harmonized Tripartite Guideline for Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial (Visit 1). 2. Clinically stable outpatients who have been diagnosed with schizophrenia (as per Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)). 3. Patients, who completed 26 weeks of treatment in the parent trial, must enter the extension trial within: • Within 2 weeks the end of treatment visit in 1346-0011, 1346-0013. • At the end of safety follow up in 1346-0012. 4. Women of childbearning potential (WOCBP) must be ready and able to use highly effective methods of birth control per Non-Clinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals (ICH M3 (R2)) that result in a low failure rate of less than 1% per year when used consistently and correctly. Such methods should be used throughout the trial, and for a period of at least 35 days after last trial drug intake, and the patient must agree to periodic pregnancy testing during participation in the trial. 5. Have a study partner, defined as any person capable of understanding trial related procedures, with a minimum of 8th grade level of education, who knows the patient well, has been capable of interacting with the patient on regular basis (at least once a week, either private or professional). Study partner does not need to attend visits with the patient but must be reachable by phone. Study partner should preferably be the same person throughout the study, if possible • Professional study partner (e.g. study nurse, social worker etc.) are allowed if not involved in administering any of the protocol assessments. |
1. Consentimiento informado escrito firmado y fechado, de acuerdo a ICH-GCP y a la regulación local antes de la admisión al ensayo (Visita 1). 2. Pacientes ambulatorios clínicamente estables con diagnóstico de esquizofrenia (según el Manual diagnóstico y estadístico de los trastornos mentales, 5.ª ed. [DSM-5]). 3. Los pacientes que hayan completado 26 semanas de tratamiento en el ensayo original deben incorporarse al estudio de extensión: o En las 2 semanas siguientes a la visita de final del tratamiento en 1346-0011, 1346-0013. o Al final del seguimiento de seguridad en 1346-0012. 4. Mujeres en edad fértil deben estar preparadas y dispuestas para utilizar métodos anticonceptivos altamente efectivos según ICH M3 (R2), que tengan una tasa de fallo inferior a 1%/año, cuando se usan de forma consistente y correcta. Estos métodos deben utilizarse durante el ensayo, y por un periodo de al menos 35 días después de la última toma de la medicación del estudio, además el paciente debe aceptar la realización de pruebas de embarazo a lo largo del ensayo. 5. Tener una pareja del estudio, definida como cualquier persona capaz de comprender los procedimientos relacionados con el estudio, con un nivel educativo mínimo equivalente a 2.º de la ESO, que conoce bien al paciente y ha podido interactuar con el paciente de forma periódica (al menos una vez a la semana, de forma privada o profesional). La pareja del estudio no es necesario que atienda a las visitas del ensayo con el paciente, pero debe estar disponible a ser contactada por teléfono. Preferiblemente debe ser la misma persona durante todo el estudio. 6. La pareja profesional del estudio (por ej. el/la enfermero/a del estudio, un/a trabajador/a social etc.) está permitido, si no involucrado/a en administrar cualquiera de las evaluaciones del protocolo. |
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E.4 | Principal exclusion criteria |
1. Participant who developed DSM5 diagnosis other than Schizophrenia or any condition that would prevent the patient from participating in the extension trial (e.g. stroke, head trauma, developed dementia, severe uncontrolled movement disorders or other significant condition since enrolment into the parent phase III trial). 2. Any suicidal behavior and/ or suicidal ideation of type 5 based on the C-SSRS in parent trial and up to and including Visit 1 of this study. o Patients with Suicidal Ideation type 4 in the C-SSRS (active suicidal thought with intent but without specific plan), in the past 3 months prior to and including Visit 1, can be entered in the study, if assessed and documented by a licensed mental health professional that there is no immediate risk of suicide. 3. Patients diagnosed with moderate or severe substance use disorder (other than caffeine and nicotine), as defined in DSM-5 while the patient was in parent trial and prior to Visit 1 of this study. 4. Positive urine drug screen ≥ 3 times during the treatment period of trial 1346-0011, 1346-0012 or 1346-0013 based on central lab test. 5. Patients who are currently or wish to participate in another investigational drug trial. 6. Any clinically significant finding in the judgment of the investigator such as : o Clinically significant finding on the Physical examination and/or ECG from the last assessment done in the parent trial. o Vital signs (including blood pressure (BP) and pulse rate (PR)) that would jeopardize the patient´s safety while participating in the trial or their capability to participate in the trial. o Symptomatic/unstable/uncontrolled or clinically relevant concomitant disease or any other clinical condition that would jeopardize the patient´s safety while participating in the trial or capability to participate in the trial. o Significant or unstable physical condition that may require change in medication or hospitalization that would impact cognitive function. 7. Any significant central lab findings based on the last available lab result received during the parent trial such as: o Severe renal impairment defined as an eGFR < 30mL/min/1.73m², o Indication of liver disease, defined by serum levels of either ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3 times upper limit or normal or o Hb drop below 100g/L (10g/dL) OR Hb decrease of 25% or more from baseline and is below lower limit of normal in parent trial (alert 3 from last measure Hb in parental trial) o Patients who meet any of the withdrawal criteria before planned end of treatment (26 weeks) in parent trial. 8. Patients who have been diagnosed with hemoglobinopathies during the parent trial. 9. Patients with known ongoing severe or serious infection with SARS-CoV-2. 10. Known history of HIV and/or known on-going Hepatitis B or C infections. As well as any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix. 11. Women who are pregnant, nursing, or who plan to become pregnant while in the trial. 12. Patients with an allergy to BI 425809 and/or any of the excipients (including serious lactose intolerance). 13. Patients who are currently treated or expected to be treated with any of the following: strong or moderate CYP3A4 inhibitors, strong or moderate CYP3A4 inducers, CYP3A4 sensitive substrates,. including grapefruit juice and St. John’s wort (Hypericum perforatum) and substrates with a narrow therapeutic range (e.g., fentanyl, cyclosporine). |
1. Participante que ha desarrollado un diagnóstico del DSM-5 distinto de la esquizofrenia o cualquier afección que pudiera impedir que el paciente participe en el ensayo de extensión (p.ej. accidente cerebrovascular, traumatismo craneal, demencia desarrollada, trastornos del movimiento incontrolados severos u otras afecciones significativas desde la participación en el ensayo de fase III original). 2. Cualquier conducta suicida y/o ideación suicida de tipo 5 basada en la escala C-SSRS en el estudio original y hasta la Visita 1, incluida, de este estudio. Pacientes con ideación suicida tipo 4 en el C-SSRS (pensamiento suicida activo con intención, pero sin plan específico), en los últimos 3 meses anteriores a la Visita 1, incluida, pueden participar en el estudio si se evalúa y se documenta por un profesional de la salud mental que no hay riesgo inmediato de suicidio. 3. Pacientes con diagnóstico de trastorno moderado o grave por consumo de sustancias (otros que no sean cafeína ni nicotina), tal y como se define en DSM-5 mientras el paciente estaba en el ensayo original o previo a la Visita 1 de este estudio. 4. Test positivo de drogas en orina ≥ 3 veces durante el periodo de tratamiento en los ensayos 1346-0011, 1346-0012 or 1346-0013 5. Pacientes que estén participando o quieran participar en otros ensayos clínicos con medicamentos. 6. Cualquier hallazgo clínicamente significativo a juicio del investigador, como: - Hallazgos clínicamente significativos en el examen físico y/o en el ECG de la última evaluación realizada en el ensayo principal - Signos vitales (incluyendo presión arterial y frecuencia cardíaca) que puedan comprometer la seguridad del paciente mientras participa en el ensayo o su capacidad para participar en el ensayo. - Enfermedad concomitante sintomática/inestable/no controlada o clínicamente relevante o cualquier otra condición clínica que pueda comprometer la seguridad del paciente mientras participa en el ensayo o su capacidad para participar en el ensayo. - Condición física significativa o inestable que pueda requerir un cambio en la medicación u hospitalización, que afecte a la función cognitiva. 7. Cualquier hallazgo significativo en el laboratorio central basado en el último resultado disponible recibido durante el ensayo original, tal como: - Insuficiencia renal grave definida como eGFR < 30 mL/min/1,73 m², o Indicación de enfermedad hepática, definida por los niveles séricos de ALT (SGPT), AST (SGOT) o fosfatasa alcalina por encima de 3 veces el límite superior o normal, - Hemoglobina: descenso de la Hb por debajo de 100 g/l (10 g/dl) O disminución de la Hb del 25 % o más respecto al valor inicial y con valores por debajo del límite inferior de la normalidad en el ensayo original (alerta 3 en la última medición de Hb en el estudio original), - Pacientes que cumplan cualquiera de los criterios de retirada antes de la finalización prevista del tratamiento (26 semanas) en el ensayo original. 8. Pacientes a los que se les ha diagnosticado hemoglobinopatías durante el ensayo original. 9. Pacientes con infección grave o grave conocida por SARSCoV-2. 10. Antecedentes conocidos de infección por VIH y/o hepatitis B o C en curso. Así como cualquier actividad documentada o sospecha de malignidad o historia de malignidad en los 5 años previos a la selección, excepto carcinoma basocelular de la piel debidamente tratado, carcinoma escamoso de la piel o carcinoma in situ del cuello uterino. 11. Mujeres que están embarazadas, en periodo de lactancia, o que planean quedarse embarazadas durante el ensayo. 12. Pacientes con alergia a BI 425809 y/o alguno de los excipientes (incluyendo intolerancia grave a la lactosa). 13. Pacientes que están siendo tratados actualmente o que se espera que reciban alguno de los siguientes tratamientos: inhibidores potentes o moderados de CYP3A4, inductores potentes o moderados del CYP3A4, sustratos sensibles al CYP3A4, incluyendo zumo de pomelo y hierba de San Juan (Hypericum perforatum) y sustratos con un estrecho rango terapéutico (por ejemplo, fentanilo, ciclosporina). |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) occurrence of treatment emergent adverse events (TEAEs) |
1) aparición de acontecimientos adversos surgidos durante el tratamiento (AAST) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) 54 weeks |
1) 54 semanas |
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E.5.2 | Secondary end point(s) |
1) Change from baseline in CGI-S to end of treatment. 2) Change from baseline in hemoglobin to end of treatment. |
1) Cambio respecto al inicio en la escala de Impresión Clínica Global-Gravedad (CGI-S) hasta el final del tratamiento 2) Cambio desde el inicio del nivel de Hb hasta el final del tratamiento. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) 52 weeks 2) 52 weeks |
1) 52 semanas 2) 52 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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 93 |
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 |
Brazil |
Chile |
China |
Colombia |
Japan |
Korea, Republic of |
Mexico |
Russian Federation |
Serbia |
Taiwan |
Ukraine |
United States |
Belgium |
Croatia |
Denmark |
Finland |
France |
Germany |
Hungary |
Italy |
Lithuania |
Netherlands |
Norway |
Poland |
Romania |
Slovakia |
Spain |
Sweden |
United Kingdom |
Czechia |
Argentina |
Greece |
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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
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 10 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 10 |