E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prodromal Alzheimer's Disease |
Enfermedad de Alzheimer (EA) prodrómica |
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E.1.1.1 | Medical condition in easily understood language |
Early Alzheimer's Disease |
Enfermedad de Alzheimer temprana |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
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 safety and tolerability of MK-8931 in the long term treatment of prodromal Alzheimer?s Disease (AD) -To compare the efficacy of MK-8931 administered to subjects for 30 months to that of subjects administered placebo for 24 months followed by MK-8931 for 6 months using the change from baseline score CDR-SB score at Week 130. |
-Evaluar la seguridad y la tolerabilidad de MK 8931 en el tratamiento a largo plazo de la enfermedad de Alzheimer (EA) prodrómica. -Comparar la eficacia de MK 8931 en sujetos tratados durante 30 meses con la observada en sujetos tratados con placebo durante 24 meses seguido de MK 8931 durante 6 meses mediante la variación con respecto al momento basal de la puntuación CDR-SB al cabo de 130 semanas. |
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E.2.2 | Secondary objectives of the trial |
-There are no secondary objectives for this long term safety trial. |
-No hay objetivos secundarios para este ensayo de seguridad a largo plazo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Have tolerated study medication and completed the initial 104-week trial. Subjects who did not complete the initial 104-weeks of treatment but continued with and completed scheduled visits may be permitted to continue in the long term extension at the discretion of the Sponsor. Subjects who repeatedly deviate from protocol requirements will not be permitted to continue in this extension. In addition, subjects who are less than 75% compliant with trial medication during the initial 104-week trial will not be permitted to continue in the long term safety extension, except in special circumstances, which require Sponsor approval. -Have a trial partner who is reliable and competent. The trial partner must have a close relationship with the subject, have face to face contact at least 3 days/week for a minimum of 6 waking hours/week (or more, based on local requirements), be willing to accompany the subject to all trial visits, and be willing to monitor compliance of the administration of the trial medication. The trial partner should understand the nature of the trial and adhere to trial requirements (e.g. dose, visit scheduled and evaluations). It is recommended that the trial partner accompany the subject to all trial visits. -Sign (or legal representative signature) the informed consent in accordance with local requirements, after the scope and nature of the trial have been explained. |
-Haber tolerado la medicación del ensayo y completado el ensayo de 104 semanas inicial. Los sujetos que no hayan completado las 104 semanas iniciales de tratamiento, pero que hayan proseguido y completado las visitas programadas, podrán participar en esta extensión a largo plazo a criterio del promotor. Los sujetos que muestren desviaciones repetidas respecto a los requisitos del protocolo no podrán incorporarse a esta extensión. Además, los sujetos cuyo cumplimiento de la medicación del ensayo haya sido inferior al 75% durante el ensayo de 104 semanas inicial no podrán participar en la extensión a largo plazo, excepto en circunstancias especiales, que requerirán la aprobación del promotor (o, cuando se exija localmente, la aprobación del investigador en lugar del promotor). -Tener un acompañante para el ensayo que sea fiable y competente. Dicho acompañante deberá tener una relación estrecha con el sujeto, mantener encuentros cara a cara al menos 3 días/semana durante un mínimo de 6 horas de vigilia/semana (o más, dependiendo de los requisitos locales), estar dispuesto a acompañar al sujeto a todas las visitas del estudio y estar dispuesto a controlar el cumplimiento de la administración de la medicación del ensayo. También deberá comprender la naturaleza del ensayo y cumplir los requisitos del mismo (por ejemplo, dosis, fechas de las visitas y evaluaciones). Se recomienda que este acompañante para el ensayo acuda a todas las visitas con el sujeto. -Firmar (él mismo o su representante legal) el documento de consentimiento informado, de conformidad con los requisitos locales, tras habérsele explicado el ámbito y la naturaleza del ensayo. |
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E.4 | Principal exclusion criteria |
-Is in imminent risk of self harm, based on clinical interview or on the Columbia Suicidality Severity Rating Scale (C-SSRS), or of harm to others in the opinion of the investigator. Subjects who report suicidal ideation with intent, with or without a plan (e.g., suicidal ideation item 4 or 5 on the C-SSRS) in the past one (1) month or suicidal behavior in the past six (6) months should be excluded. Such subjects will be permitted to rescreen for entry into this study once in the Investigator?s opinion, this risk of harm to self or others is no longer present. -Has developed a recent or ongoing, uncontrolled, clinically significant medical or psychiatric condition that precludes participation in this protocol in the judgment of the investigator. -Based on results from the EOT Visit (Visit 12) in the initial 104-week trial has results of clinical laboratory tests (complete blood count [CBC], blood chemistries, and urinalysis) that are clinically unacceptable to the investigator. -Based on the results from the EOT Visit (Visit 12) has results of a physical examination, and vital signs that are clinically unacceptable to the investigator. -Has developed a form of dementia that is not Alzheimer's disease, including but not limited to, dementia due to HIV infection, head trauma, vascular disease, Parkinson's disease, frontotemporal dementia, or Huntington's disease, as determined by the investigator. -Anticipates receiving any of the treatments listed as prohibited. |
-Corre un riesgo inminente de autolesión, basándose en una entrevista clínica o en la Escala de valoración de la intensidad de la tendencia suicida de Columbia (C-SSRS), o de lesionar a terceros, según la opinión del investigador. Quedarán excluidos los sujetos que refieran ideación suicida con intención, con o sin un plan (por ejemplo, apartado de ideación suicida 4 o 5 en la escala C-SSRS), en el mes precedente o conductas suicidas en los seis meses precedentes. En estos sujetos podrá repetirse la selección para poder participar en este estudio una vez que, en opinión del investigador, ya no esté presente el riesgo de autolesión o de lesionar a terceros. -Ha contraído una afección médica o psiquiátrica de importancia clínica y no controlada, reciente o todavía activa, que impide la participación en este protocolo, a criterio del investigador. -A tenor de los resultados de la visita de FDT (visita 12) del ensayo de 104 semanas inicial, presenta unos resultados analíticos (hemograma completo, bioquímica sanguínea y análisis de orina) que son clínicamente inaceptables para el investigador. -A tenor de los resultados de la visita de FDT (visita 12), presenta unos resultados de la exploración física o las constantes vitales que son clínicamente inaceptables para el investigador. -Ha desarrollado una forma de demencia que no es enfermedad de Alzheimer, incluyendo, pero no limitado a demencia debida a la infección por el VIH, traumatismo craneoencefálico, vasculopatía, enfermedad de Parkinson, demencia frontotemporal o enfermedad de Huntington, según lo determinado por el investigador. -Prevé recibir alguno de los tratamientos que se citan en la tabla 1 del protocolo durante el presente ensayo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change from baseline (CFB) in CDR-SB score at Week 130. |
La variable principal de la eficacia es la variación con respecto al momento basal (VRMB) de la puntuación CDR-SB al cabo de 130 semanas. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline and Week 130. |
Visita basal y semana 130 |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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) | 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 | 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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
grupos paralelos |
paralell groups |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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 |
Austria |
Belgium |
Brazil |
Canada |
Finland |
France |
Germany |
Hungary |
Italy |
Japan |
Korea, Republic of |
Netherlands |
New Zealand |
Norway |
Poland |
Spain |
Switzerland |
United Kingdom |
United States |
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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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The study is expected to last up to approximately five years or until a) MK-8931 becomes commercially available (locally), or b) when the MK-8931 program is terminated (whichever comes first). |
Se esperan que el estudio dure 5 años o hasta que el: -MK-8931 se comercialice localmente o cunado el programa MK-8931 se haya terminado (lo que ocurra antes). |
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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 | |
E.8.9.1 | In the Member State concerned months | 60 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 60 |