E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild to moderate Alzheimer's disease |
Enfermedad de Alzheimer leve a moderada |
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E.1.1.1 | Medical condition in easily understood language |
Mild to moderate Alzheimer's disease |
Enfermedad de Alzheimer leve a moderada |
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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 | 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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066571 |
E.1.2 | Term | Progression of 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 investigate the safety and tolerability of 600mg bid of LM11A-31-BHS (free base) administered for a period of 10 days in comparison to placebo. Safety will be assessed through adverse event reporting, clinical laboratory, ECG and a standard range of patient physical evaluations. |
Investigar la seguridad y tolerabilidad de 600 mg b.i.d. de LM11A-31-BHS administradas por vía oral a voluntarios ancianos sanos durante un período de 10 días en comparación con placebo. |
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E.2.2 | Secondary objectives of the trial |
To investigate the systemic pharmacokinetics of 600 mg b.i.d. doses of LM11A-31-BHS administered orally for a period of 10 days in healthy elderly volunteers. To evaluate cerebrospinal fluid (CSF) levels of LM11A-31-BHS under the conditions of this trial. |
Investigar la farmacocinética sistémica de 600 mg b.i.d. de LM11A-31-BHS administradas por vía oral durante un período de 10 días en voluntarios ancianos sanos. Evaluar los niveles de líquido cefalorraquídeo (LCR) de LM11A-31-BHS bajo las condiciones de este ensayo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Men and women (non-childbearing potential) 2. Age 60-85 years 3. Formal education for eight or more years 4. Volunteers living at home or nursing home setting without continuous nursing care 5. General health status acceptable for a participation in a 10-day clinical trial 6. Stable pharmacological treatment of any other chronic condition for at least one month prior to screening 7. No regular intake of prohibited medications as noted in Section 6.8. 8. Signed informed consent by volunteer prior to the initiation of any study specific procedure |
1. Hombres y mujeres (en edad no fértil). 2. Edad entre 60-85 años. 3. Educación formal de 8 años o más. 4. Voluntarios que vivan en su hogar o en una residencia de ancianos sin atención de enfermería continua. 5. Estado de salud en general aceptable para participar en un ensayo clínico de 10 días. 6. Tratamiento farmacológico estable de cualquier otra afección crónica durante al menos un mes antes de la valoración general. 7. Que no tome regularmente alguno de los medicamentos prohibidos como se indica en la Section 6.8. 8. Que el Consentimiento Informado esté firmado por el voluntario antes del inicio de cualquier procedimiento especifico del ensayo. |
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E.4 | Principal exclusion criteria |
1. Failure to perform screening or baseline examinations 2. Hospitalization or change of chronic concomitant medication one month prior to screening or during screening period 3. A current DSM-IV diagnosis of active major depression, schizophrenia or bipolar disorder 4. Clinically significant, advanced or unstable disease that may interfere with primary or secondary variable evaluations, and which may bias the assessment of the clinical or mental status of the volunteer or put the volunteer at special risk, such as: • chronic liver disease, liver function test abnormalities or other signs of hepatic insufficiency (ALT, AST, Gamma GT, alkaline phosphatase > 2.5 ULN) • Respiratory insufficiency • Renal insufficiency (serum creatinine > 2mg/dL) or creatinine clearance ≤ 30 mL/min according to Cockcroft-Gault formula). In case of creatinine clearance ≤ 30mL/min, an alternative verification of the renal function must be completed using Cystatin C analysis. In case of normal level of Cystatin C, the volunteer can be included. • Heart disease (myocardial infarction, unstable angina, heart failure, cardiomyopathy within six months before screening) • Bradycardia (heart beat < 50/min.) or tachycardia (heart beat > 95/min.) • Hypertension (<180/95) or hypotension requiring treatment with more than three drugs • AV block (type II / Mobitz II and type III), congenital long QT syndrome, sinus node dysfunction or prolonged QTcF-interval (males >450 and females >470 msec) • Uncontrolled diabetes defined by HbA1c >8.5 • Malignant tumors within the last five years except skin malignancies (other than melanoma) or indolent prostate cancer • Metastases • Dysphagia, or any inability to swallow capsules, any known malabsorption or malassimilation syndromes and any gastrointestinal condition which might affect drug absorption, as judged by the investigator. 5. Disability that may prevent the volunteer from completing all study requirements (e.g. blindness, deafness, severe language difficulty, etc.) 6. Contraindication to lumbar puncture 7. Women who are fertile and of childbearing potential 8. Chronic daily drug intake of ≥ 14 days or expected for ≥ 14 days: • Benzodiazepines, neuroleptics or major sedatives • Antiepileptics • Centrally active anti-hypertensive drugs (clonidine, l-methyl DOPA, guanidine, guanfacine, etc.) • Opioid containing analgesics 9. Suspected or known drug or alcohol abuse, i.e., more than approximately 60 g alcohol (approximately 1 liter of beer or 0.5 liter of wine) per day indicated by elevated MCV significantly above normal value at screening in the absence of other etiology. 10. Suspected or known allergy to any components of the study treatments 11. Enrollment in another investigational study or intake of investigational drug within the previous three months 12. Any condition, which, in the opinion of the Investigator, makes the volunteer unsuitable for inclusion |
1. Fallo de screening 2. Hospitalización o cambio de medicamentos concomitantes crónicos un mes antes o durante el periodo de screening. 3. Un diagnostico DSM-IV actual de depresión mayor activa, esquizofrenia o trastorno bipolar 4. Enfermedad clínicamente significativa, avanzada o inestable que pueda interferir con las evaluaciones de variables primarias o secundarias y que puede sesgar la evaluación del estado clínico o mental del voluntario o poner al voluntario en un riesgo especial, como por ejemplo: • Enfermedades hepáticas crónicas, anomalías en las pruebas de función hepática u otros signos de insuficiencia hepática (ALT, AST, Gamma GT, fosfatasa alcalina > 2.5 ULN) • Insuficiencia respiratoria. • Insuficiencia renal (creatinina sérica > 2mg/dL) o aclaramiento de creatinina ≤ 30 mL/min según la fórmula de Cockcroft-Gault ). En caso de aclaramiento de creatinina ≤ 30mL/min, se debe completar una verificación alternativa de la función renal mediante el análisis de Cistatina-C. En caso de niveles normales de Citastina-C el voluntario podrá ser incluido. • Enfermedad cardíaca (infarto de miocardio, angina inestable, insuficiencia cardíaca, miocardiopatía dentro de los seis primeros meses previos a la valoración) • Bradicardia (latido del corazón < 50/min.) o taquicardia (latido del Corazón > 95/min.) • Hipertensión (<180/95) o hipotensión que requiera tratamiento con medicación de más de 3 fármacos. • Bloqueo AV (tipo II / Mobitz II y tipo III), síndrome de QT congénito prolongado, disfunción del nódulo sinusal o intervalo QTcF (hombres >450 y mujeres >470 mseg) • Diabetes no controlada definida HbA1c >8.5 • Tumores malignos en los últimos cinco años, excepto neoplasias malignas ( que no sean melanoma) o cáncer de próstata indolente. • Metastasis • Disfagia o cualquier incapacidad para tragar cápsulas, síndrome de mala absorción o mala asimilación conocidos y cualquier condición gastrointestinal que pueda afectar la absorción del fármaco, según lo juzgue el investigador 5. Discapacidad que puede evitar que el voluntario complete todos los requisitos del estudio (por ejemplo, ceguera, sordera, dificultad grave de lenguaje, etc) 6. Contraindicación para la punción lumbar 7. Mujeres en edad fértil 8. Ingesta diaria crónica de medicamento ≥ 14 días o esperada para ≥ 14 días: • Benzodiazepinas, neurolépticos o sedantes importantes • Antiepilépticos • Medicamentos antihipertensivos centralmente activos (clonidina, l-methyl DOPA, guanidina, guanfacina, etc.) • Analgésicos que contienen opiáceos. 9. Sospecha o abuso de drogas o de alcohol, es decir, más de 60 g alcohol (aproximadamente 1 litro de cerveza o 0,5 litro de vino) por día indicado por MCV elevado significativamente por encima del valor normal en la detección en ausencia de otra etiología. 10. Sospecha de alergia a cualquier componente de los tratamientos del estudio. 11. Estar participando en otro estudio de investigación o haber participado en algún ensayo clínico con medicamentos en los tres meses previos. 12. Cualquier condición que, en opinión del investigador, haga que el voluntario no sea apto para su inclusión. |
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E.5 End points |
E.5.1 | Primary end point(s) |
All safety evaluations will be summarized as interval or categorical summaries as appropriate. The overall incidence of adverse events, together with the top three most frequently reported adverse events, will be analyzed using a binary logistic model to demonstrate differences between the treatment groups and placebo. The end points include alls Adverse events (AEs), Serious adverse events (SAEs), Clinical Diagnostics, Vital signs (blood pressure, heart rate, respiratory rate, body temperature), ECG, Laboratory assessment (hematology, biochemistry, serology and urinalysis) |
Todas las evaluaciones de seguridad se resumirán en resúmenes por intervalos o por categorías, según corresponda. La incidencia general de eventos adversos, junto con los tres eventos adversos notificados con mayor frecuencia, se analizará utilizando un modelo logístico binario para demostrar diferencias entre los grupos de tratamiento y el placebo. Los signos vitales (presión arterial, frecuencia cardiaca, frecuencia respiratoria, temperatura corporal), ECG, evaluación de laboratorio (hematología, bioquímica, serología y otros), efectos adversos graves (EAE) Análisis de orina) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Changes between baseline and end of study visit (10days) |
Cambios entre el inicio y el final de la visita de estudio (10 dias) |
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E.5.2 | Secondary end point(s) |
PK measurements: • AUC(0-t), AUC(0-∞), Cmax, Tmax, t1/2, ClF, Vd Safety in blood and CSF |
Medidas PK: • AUC (0-t), AUC (0-∞), Cmax, Tmax, t1 / 2, ClF, Vd Seguridad en sangre y LCR |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Changes between baseline and end of study visit (10days) |
Cambios entre el inicio y el final de la visita de estudio (10 dias) |
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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 | No |
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) | 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 | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |