E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with diagnosis of AD according to the following criteria: ? Symptoms noticed by the patients and/or informant ? Cognitive testing confirming symptoms ? Biomarker evidence of AD pathology ? No evidence of other forms of dementia ? No other concomitant illness or medication which could confound or prohibit completion in the trial by the patient |
Pacientes con diagnóstico de AD según los siguientes criterios: -Síntomas referidos por los pacientes y/o los informantes -Evaluación cognitiva que confirme los síntomas -Resultados de los biomarcadores indicativos de AD -Sin evidencias de otras formas de demencia -Sin otra enfermedad concurrente o medicación concomitante que pudieran inducir a una interpretación errónea o impedir la finalización del estudio por el paciente |
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E.1.1.1 | Medical condition in easily understood language |
Patients who suffer by mental disorders which are caused by symptoms of the Alzheimer's Disease |
Pacientes que sufren trastornos mentales causados por los síntomas de la enfermedad de Alzheimer |
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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 | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
E.1.2 | System Organ Class | 100000004852 |
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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 assess efficacy of different doses of BI 409306 compared to placebo in treatment of Alzheimers' Disease (AD) |
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E.2.2 | Secondary objectives of the trial |
To assess safety and tolerability of different doses of BI 409306 compared to placebo in treatment of Alzheimers' Disease (AD) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male and female patients with an age of at least 55 years
- Body weight not lower than 50 kgs
- Patients with a confirmed diagnosis of AD
- Treatment naive patients or patients who have not received prescribed drugs for treatment of AD (including acetyl cholinesterase inhibitors (donepezil, galantamine, rivastigmine, tacrine, phenserine) and Memantine
- Patients must have at least 6 years of formal education and fluency in the test language as verbally confirmed by the patient and documented by the study investigator.
- Patients must have given written informed consent in accordance with Good Clinical Practice (GCP) and local legislation prior to any study procedures. All patients must be able to give informed consent personally and have capacity for such consent. An informed consent given by a legal representative will not be accepted.
- Patients must have a reliable study partner (per investigator judgement, for instance a family member, guardian, partner etc.) |
-Pacientes de ambos sexos con ? 55 años. -Peso corporal ? 50 kg. -Pacientes con diagnóstico confirmado de AD -Pacientes naive de tratamiento o pacientes que no hayan recibido fármacos prescritos para el tratamiento de la AD (que incluyen los inhibidores de la acetilcolinesterasa[donepezilo, galantamina, rivastigmina, tacrina, fenserina] y memantina). - Los pacientes deben tener un mínimo de 6 años de nivel educativo formal y fluidez en el idioma de las pruebas, lo que el paciente deberá confirmar verbalmente y documentado por el investigador del estudio. -Los pacientes deberán haber dado su consentimiento informado por escrito de conformidad con las GCP y la legislación local antes de realizar cualquier procedimiento del estudio. Todos los pacientes deben poder otorgar el consentimiento informado personalmente y tener capacidad para otorgarlo. No se aceptará un consentimiento informado otorgado por un representante legal. -Los pacientes deben tener un pariente/cuidador del estudio fiable (según el criterio del investigador, por ejemplo, un miembro de su familia, pareja, etc., cuidador/tutor) |
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E.4 | Principal exclusion criteria |
- Cognitive impairment with any etiology other than AD (based on clinical data and/or current laboratory findings and/or a pre-existing MRI or CT of the brain which is not older than 12 months prior to screening visit) for example: neurosyphilis, craniocerebral trauma, small vessel disease
- Substantial concomitant cerebrovascular disease (defined by a history of a stroke / intracranial haemorrhagia) temporally related to the onset of worsening of cognitive impairment per investigator judgement
- Medical history of cancer (except for basal cell carcinoma) and/or treatment for cancer within the last 5 years
- Medical history or diagnosis of any of symptomatic and unstable/uncontrolled conditions per investigator judgement
- Severe renal impairment defined with a glomerular filtration rate (GFR) < 30ml/min/1.73m2 in the screening central lab report
- Any other psychiatric disorders such as schizophrenia, or mental retardation
- Any suicidal actions in the past 2 years (per investigator judgement i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behaviour)
- Any suicidal ideation of type 4 or 5 in the Columbia Suicide Severity Rating Scale (C-SSRS) in the past 3 months (i.e. active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent)
- Previous participation in investigational drug studies of cognitive impairment. Currently ongoing treatment with non-prescription medications, vitamins or other nutritional formulations is allowed however these should be captured in the electronic case report form (e-CRF)
- Significant history of drug dependence or abuse (including alcohol, as defined in Diagnostic and Statistical Manual of Mental Disorders (DSM-V) or in the opinion of the investigator) within the last two years, or a positive urine drug screen for cocaine, heroin, or marijuana
- Known history of HIV infection
- Any planned surgeries requiring general anaesthesia, or hospitalisation for more than 1 day during the study period
- Pre-menopausal women (last menstruation = 1 year prior to informed consent) who are nursing or pregnant or are of child-bearing potential and are not practicing an acceptable method of birth control
- For male patients: Men who are able to father a child, unwilling to be abstinent or to use an adequate form of effective contraception for the duration of study participation and for at least 28 days after treatment has ended.
- Use of any investigational drug or procedure for other indications within 3 months or 6 half-lives (whichever is longer) prior to randomization.
- Intake of medications which might interfere with the study drug within 3 months prior to randomization and intended to be initiated during the duration of the trial
- Clinically significant uncompensated hearing loss in the judgment of the investigator. Use of hearing aids is allowed.
- Known hypersensitivity to the drug product excipients. |
-Deterioro cognitivo de cualquier etiología distinta a AD (según los datos clínicos y/o resultados analíticos de laboratorio actuales y/o en una MRI o CT cerebral preexistente realizada como máximo 12 meses antes de la visita de selección) por ejemplo: neurosífilis, traumatismo craneoencefálico o enfermedad de los vasos pequeños. -Enfermedad cerebrovascular concomitante importante (definida por antecedentes de ictus/hemorragia intracraneal) relacionada temporalmente con el inicio de un empeoramiento del deterioro cognitivo, según el criterio del investigador. - Antecedentes de cáncer (excepto carcinoma basocelular) y/o tratamiento para el cáncer en los últimos 5 años. -Antecedentes médicos u diagnóstico de cualquiera de las enfermedades sintomáticas y no controladas/inestables, según el criterio del investigador. -Insuficiencia renal grave definida como una GFR < 30 ml/min/1,73 m2 en el informe del laboratorio central de la visita de selección. -Cualquier otro trastorno psiquiátrico, como esquizofrenia o retraso mental. -Cualquier acción suicida en los últimos 2 años (según el criterio del investigador, p. ej., intento real, intento interrumpido, intento abortado o actos o comportamientos preparatorios). -Cualquier tipo de ideación suicida de tipo 4 o 5 en la Escala de valoración de gravedad de la conducta suicida de la Universidad de Columbia (C-SSRS) en los últimos 3 meses (es decir, pensamiento suicida activo con intención pero sin planificación específica, o pensamiento suicida activo con planificación e intención). -Participación anterior en estudios de fármacos en investigación para el deterioro cognitivo leve. Se permite el tratamiento concomitante actual con medicamentos de venta sin receta, vitaminas u otros complementos nutricionales, aunque deberán registrarse en el e-CRF. - Antecedentes significativos de dependencia o abuso de drogas o alcohol (según el criterio del investigador) en los dos años anteriores o un resultado positivo en la prueba de detección en orina para cocaína, heroína o marihuana. -Antecedentes de infección por el HIV. -Cualquier intervención quirúrgica programada que requiera anestesia general, u hospitalización de más de 1 día durante el periodo del estudio. -Mujeres premenopáusicas (última menstruación ? 1 año antes del consentimiento informado) que: ? estén en periodo de lactancia o embarazadas, o ? puedan quedarse embarazadas y no utilicen un método anticonceptivo fiable -En el caso de los pacientes varones: varones que puedan engendrar un niño y no acepten la abstinencia sexual ni el uso de un método anticonceptivo eficaz durante la participación en el estudio y durante al menos 28 días después de la finalización del tratamiento. -Uso de cualquier fármaco o procedimiento en investigación para otras indicaciones en el plazo de 3 meses o 6 vidas medias (lo que sea más largo) antes de la aleatorización. -Administración de medicamentos en las 3 meses previos a la aleatorización y que se prevea iniciar su uso durante el estudio. -Pérdida de audición descompensada clínicamente significativa, según el criterio del investigador. Se permite el uso de los audífonos. -Hipersensibilidad conocida a los excipientes del fármaco |
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E.5 End points |
E.5.1 | Primary end point(s) |
1: The primary endpoint is Neuropsychological Test Battery (NTB) response, defined as change from baseline in total score after 12-week treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1: Change from baseline in ADCS-MCI-ADL (Alzheimer's Disease Cooperative Study/Activities of Daily Living scale adapted for MCI patients) total score after 12-week treatment. 2: Change from baseline in ADCS-ADL (Alzheimer's Disease Cooperative Study/Activities of Daily Living) total score after 12-week treatment. 3: Change from baseline CDR-SB (Clinical Dementia Rating, Sum of Boxes) after 12-week treatment 4: Change from baseline in ADAS-Cog11 (Alzheimers Disease Assessment Scale cognitive subscale) total score after 12-week treatment. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: 12 weeks 2: 12 weeks 3: 12 weeks 4: 12 weeks |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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) | 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 | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 5 |
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 | 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 |
Austria |
Belgium |
Canada |
France |
Germany |
Italy |
Netherlands |
Poland |
Portugal |
Spain |
United Kingdom |
United States |
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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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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 | 10 |
E.8.9.1 | In the Member State concerned days | 9 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 11 |