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    Summary
    EudraCT Number:2015-005263-16
    Sponsor's Protocol Code Number:NSC15001
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2017-06-22
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2015-005263-16
    A.3Full title of the trial
    A 6-months prospective, multi-center, double-blind, placebo-controlled, randomized, adaptive-trial-design study to evaluate safety, tolerability and exploratory endpoints of either placebo or two different oral doses of LM11A-31-BHS in patients with mild to moderate probable Alzheimer’s disease.
    Estudio prospectivo de 6 meses de duración , multicéntrico, doble ciego, controlado con placebo, aleatorizado con un diseño adaptado para evaluar la seguridad, la tolerabilidad y valoración preliminar de eficacia tanto del placebo como de dos dosis orales de LM11A-31-BHS en pacientes con enfermedad de Alzheimer de leve a moderada.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical study performed at several sites with a treatment duration of 6 months, with 3 treatment arms (2 different dosages LM11A-31-BHS and 1 placebo), which are randomly distributed in a double-blind manner (neither physician nor patient will know which treatment arm) between the patients to evaluate safety, tolerability and other questions of research of the two different oral dosages of LM11A-31-BHS in comparison with placebo in patients with mild to moderate probable Alzheimer’s disease
    Se realizó un estudio clínico en varios sitios con una duración de tratamiento de 6 meses, con 3 brazos de tratamiento (2 dosis diferentes LM11A-31-BHS y 1 placebo) distribuidos al azar de manera doble ciega entre los pacientes para evaluar la seguridad, tolerabilidad y otras cuestiones de investigación de las dos diferentes dosis orales de LM11A-31-BHS en comparación con placebo, en pacientes con enfermedad de Alzheimer leve a moderada.
    A.4.1Sponsor's protocol code numberNSC15001
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorPharmatrophix Inc
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportPharmatrophix Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNeuroScios GmbH
    B.5.2Functional name of contact pointCRO
    B.5.3 Address:
    B.5.3.1Street AddressWillersdorferstrasse 7
    B.5.3.2Town/ citySt. Radegund
    B.5.3.3Post code8061
    B.5.3.4CountryAustria
    B.5.4Telephone number004331324044412
    B.5.5Fax number004331324044420
    B.5.6E-mailnhelmberg@neuroscios.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameLM11A-31-BHS
    D.3.2Product code LM11A-31-BHS
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLM11A-31-BHS
    D.3.9.2Current sponsor codeLM11A-31-BHS
    D.3.9.3Other descriptive nameLM11A-31-BHS
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule, hard
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Mild to moderate Alzheimer's disease
    Enfermedad de Alzheimer leve a moderada
    E.1.1.1Medical condition in easily understood language
    Mild to moderate Alzheimer's disease
    Enfermedad de Alzheimer leve a moderada
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10001896
    E.1.2Term Alzheimer's disease
    E.1.2System Organ Class 100000004852
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10066571
    E.1.2Term Progression of Alzheimer's disease
    E.1.2System Organ Class 100000004852
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To investigate the safety and tolerability of 200mg bid and 400mg bid doses of LM11A-31-BHS (free base) administered for a period of 26 weeks in comparison to placebo.
    Safety will be assessed through adverse event reporting, clinical laboratory, ECG and a standard range of patient physical evaluations including a suicide severity rating scale (C-SSRS).
    Investigar la seguridad y la tolerabilidad de 200 mg de dosis de oferta y 400 mg de dosis de LM11A-31-BHS (base libre) administradas durante un período de 26 semanas en comparación con el placebo.
    La seguridad se evaluará a través de informes de acontecimientos adversos, laboratorio clínico, ECG y un rango estándar de evaluaciones físicas del paciente, incluyendo una escala de clasificación de gravedad del suicidio (C-SSRS).
    E.2.2Secondary objectives of the trial
    Exploratory investigation of relevant biomarkers for AD and drug mechanism including regional brain glucose metabolism (18F-FDG-PET) and CSF measures.
    The assessment of exploratory clinical endpoints including a composite of the specific cognitive tests performed (the NTB composite standardized Z score).
    The investigation of the pharmacokinetics of 200mg bid and 400mg bid doses of LM11A-31-BHS (free base) administered for a period of 26 weeks. PK parameters for LM11A-31 and its aminoethyl morpholine metabolite will be estimated using noncompartmental analysis (NCA).
    Investigación exploratoria de biomarcadores relevantes para la AD y el mecanismo del fármaco incluyendo el metabolismo regional de la glucosa cerebral (18F-FDG-PET) y las medidas del LCR.
    La evaluación de los puntos finales clínicos exploratorios incluyendo una combinación de las pruebas cognitivas específicas realizadas (la puntuación Z normalizada estandarizada de NTB).
    La investigación de la farmacocinética de dosis de 200 mg y 400 mg de LM11A-31-BHS (base libre) administrada durante un período de 26 semanas. Los parámetros de PK para LM11A-31 y su metabolito aminoetil morfolina se estimarán mediante análisis no compartimental (NCA).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Men and women (non-childbearing potential) with a diagnosis of Alzheimer’s disease according to McKhann (2011) criteria
    2. Age 50 - 85 years
    3. MRI or CT assessment within six months before baseline, corroborating the clinical diagnosis of AD and excluding other potential causes of dementia, especially cerebrovascular lesions (see exclusion criteria, number 3)
    4. CSF AD specific biomarker profile; positive, defined as CSF Aβ42 <530 ng l−1 together with either of T-tau>350 ng l−1 or p-tau >60 ng  −1
    5. Mild to moderate stage of Alzheimer’s disease according to MMSE ≥18 and ≤26
    6. Absence of major depressive disease according to GDS of < 5
    7. Modified Hachinski Ischemic Scale ≤4
    8. Formal education for eight or more years
    9. Previous decline in cognition for more than six months as documented in patient medical records
    10. A caregiver available and living in the same household or interacting with the patient a sufficient time each week and available if necessary to assure administration of drug
    11. Patients living at home or nursing home setting without continuous nursing care
    12. General health status acceptable for a participation in a 6-month clinical trial
    13. Ability to swallow capsules
    14. Stable pharmacological treatment of any other chronic condition for at least one month prior to screening
    15. Stable treatment with one of the acetylcholinesterase inhibitors donepezil (Aricept ®), galantamine (Razadyne®), or rivastigmine (Exelon) or the partial NMDA receptor antagonist with memantine (Namenda®) at least 3-months before baseline Visit or Combination of both treatments mentioned above
    16. No regular intake of prohibited medications as noted in Section 11.8. of the protocol
    17. Signed informed consent by caregiver and patient prior to the initiation of any study specific procedure.
    1. Hombres y mujeres (potenciales no procreables) con diagnóstico de enfermedad de Alzheimer según los criterios de McKhann (2011)
    2. Edad 50 - 85 años
    3. Evaluación de RM o TAC dentro de los seis meses anteriores al inicio del estudio, corroborando el diagnóstico clínico de la EA y excluyendo otras causas potenciales de demencia, especialmente lesiones cerebrovasculares (ver criterios de exclusión, número 3)
    4. Perfil del biomarcador específico del LCR del CEF; Positivo, definido como CSF ​​Aβ42 <530 ng l-1 junto con cualquiera de T-tau> 350 ng l-1 o p-tau> 60 ng -1
    5. Etapa leve a moderada de la enfermedad de Alzheimer según MMSE ≥18 y ≤26
    6. Ausencia de enfermedad depresiva mayor según GDS de <5
    7. Escala isquémica de Hachinski modificada ≤4
    8. Educación formal durante ocho o más años
    9. Descenso anterior de la cognición por más de seis meses, tal como se documenta en los registros médicos del paciente
    10. Un cuidador disponible y viviendo en el mismo hogar o interactuando con el paciente un tiempo suficiente cada semana y disponible si es necesario para asegurar la administración del medicamento
    11. Pacientes que viven en el hogar o el asilo de ancianos sin cuidados de enfermería continua
    12. Estado de salud general aceptable para participar en un ensayo clínico de 6 meses
    13. Capacidad para tragar las cápsulas
    14. Tratamiento farmacológico estable de cualquier otra afección crónica durante al menos un mes antes del cribado
    15. Tratamiento estable con uno de los inhibidores de la acetilcolinesterasa donepezilo (Aricept®), galantamina (Razadyne®) o rivastigmina (Exelon) o el antagonista parcial del receptor NMDA con memantina (Namenda®) al menos 3 meses antes de la visita inicial o combinación de Ambos tratamientos mencionados anteriormente
    16. Ningún consumo regular de medicamentos prohibidos como se indica en la Sección 11.8. Del protocolo
    17. El consentimiento informado firmado por el cuidador y el paciente antes del inicio de cualquier procedimiento específico del estudio.
    E.4Principal 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. Clinical, laboratory or neuro-imaging findings consistent with:
    • Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal dementia, Huntington’s disease, Creutzfeldt-Jakob Disease, Down's syndrome, etc.)
    • Other neurodegenerative condition (Parkinson’s disease, amyotrophic lateral sclerosis, etc.)
    • Cerebrovascular disease (major infarct, one strategic or multiple lacunar infarcts, extensive white matter lesions > one quarter of the total white matter)
    • Other central nervous system diseases (severe head trauma, tumors, subdural hematoma or other space occupying processes, etc.)
    • Seizure disorder
    • Other infectious, metabolic or systemic diseases affecting central nervous system (syphilis, present hypothyroidism, present vitamin B12 or folate deficiency, serum electrolytes out of normal range, juvenile onset diabetes mellitus, etc.)
    4. A current DSM-IV diagnosis of active major depression, schizophrenia or bipolar disorder
    5. 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 patient or put the patient 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 patient 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 QTcB-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
    6. Disability that may prevent the patient from completing all study requirements (e.g. blindness, deafness, severe language difficulty, etc.)
    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. Nootropic drugs
    10. 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
    11. Suspected or known allergy to any components of the study treatments
    12. Enrollment in another investigational study or intake of investigational drug within the previous three months
    13. Any condition, which, in the opinion of the investigator, makes the patient unsuitable for inclusion
    1. Incumplimiento de exámenes de cribado o de base
    2. Hospitalización o cambio de medicación concomitante crónica un mes antes del cribado o durante el período de cribado
    3. Hallazgos clínicos, de laboratorio o de neuroimagen consistentes con:
    • Otras demencias degenerativas primarias, (demencia con cuerpos de Lewy, demencia fronto-temporal, enfermedad de Huntington, enfermedad de Creutzfeldt-Jakob, síndrome de Down, etc.)
    • Otras afecciones neurodegenerativas (enfermedad de Parkinson, esclerosis lateral amiotrófica, etc.)
    • Enfermedad cerebrovascular (infarto grave, un infarto lacunar estratégico o múltiple, lesiones extensas de sustancia blanca> un cuarto de la sustancia blanca total)
    • Otras enfermedades del sistema nervioso central (trauma grave de la cabeza, tumores, hematoma subdural u otros procesos de ocupación del espacio, etc.)
    • Trastorno convulsivo
    • Otras enfermedades infecciosas, metabólicas o sistémicas que afectan al sistema nervioso central (sífilis, hipotiroidismo actual, deficiencia de vitamina B12 o folato presente, electrolitos séricos fuera de la normalidad, diabetes mellitus juvenil, etc.)
    4. Un diagnóstico actual de DSM-IV de depresión mayor activa, esquizofrenia o trastorno bipolar
    5. Enfermedad clínicamente significativa, avanzada o inestable que pueda interferir con las evaluaciones de las variables primarias o secundarias, y que pueda sesgar la evaluación del estado clínico o mental del paciente o poner al paciente en un riesgo especial, como:
    • Enfermedad hepática crónica, anomalías de la función hepática o otros signos de insuficiencia hepática (ALT, AST, Gamma GT, fosfatasa alcalina> 2,5 LSN)
    • Insuficiencia respiratoria
    • Insuficiencia renal (creatinina sérica> 2 mg / dl) o aclaramiento de creatinina ≤ 30 ml / min según la fórmula de Cockcroft-Gault. En caso de un aclaramiento de creatinina ≤ 30 ml / min, debe realizarse una verificación alternativa de la función renal utilizando el análisis de Cistatina C. En el caso de un nivel normal de Cistatina C, el paciente puede ser incluido
    • Enfermedad cardíaca (infarto de miocardio, angina inestable, insuficiencia cardiaca, cardiomiopatía dentro de los seis meses previos a la detección)
    • Bradicardia (latido del corazón <50 / min.) O taquicardia (ritmo cardíaco> 95 / min.)
    • Hipertensión (> 180/95) o hipotensión que requiere tratamiento con más de tres fármacos
    • bloqueo AV (tipo II / Mobitz II y tipo III), síndrome de QT largo congénito, disfunción del nodo sinusal o intervalo QTcB prolongado (varones> 450 y hembras> 470 mseg)
    • La diabetes no controlada definida por HbA1c> 8.5
    • Tumores malignos en los últimos cinco años, excepto tumores malignos de la piel (distintos del melanoma) o indolente
    • Metástasis
    6. Discapacidad que puede impedir que el paciente complete todos los requisitos del estudio (por ejemplo, ceguera, sordera, dificultad severa en el lenguaje, etc.)
    7. Mujeres que son fértiles y en edad fértil
    8. Ingesta diaria crónica de fármacos de ≥ 14 días o esperada durante ≥ 14 días:
    • Benzodiazepinas, neurolépticos o sedantes mayores
    • Antiepilépticos
    • Antihipertensivos con actividad central (clonidina, l-metil DOPA, guanidina, guanfacina, etc.)
    • Analgésicos que contienen opiáceos
    9. Medicamentos nootrópicos
    10. Sospechoso o conocido abuso de drogas o alcohol, es decir, más de aproximadamente 60 g de 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 el cribado
    11. Alergia sospechada o conocida a cualquier componente de los tratamientos del estudio
    12. Inscripción en otro estudio en investigación o consumo de fármaco en investigación dentro de los tres meses previos
    13. Cualquier condición que, a juicio del investigador, haga al paciente inadecuado para su inclusión
    E.5 End points
    E.5.1Primary 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, coagulation, serology and urinalysis), Columbia-Suicide Severity Rating Scale (C-SSRS), MRI scans (analyzed by a central reader)
    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, coagulación, serología y otros), efectos adversos graves (EAE) Análisis de orina), Columbia-Suicide Severity Rating Scale (C-SSRS), exploraciones de MRI (analizadas por un lector central)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Changes between baseline and end of study visit (26 weeks)
    Cambios entre el inicio y el final de la visita de estudio (26 semanas)
    E.5.2Secondary end point(s)
    All exploratory efficacy variables will be analyzed at the endpoint (Final visit). The analyses will involve the change from baseline in the NTB composite summary Z score calculated after 6 months (26 weeks) of treatment. This will involve an Analysis Of Covariance Variance (ANCOVA) model incorporating the baseline score and country as covariates.

    Additional analyses will involve evaluation of the time course of treatment response over the treatment period, using a repeated measures mixed model Analysis of Covariance (ANCOVA) for evaluation. 18F-Pet Scan variables will be analyzed in a descriptive and exploratory manner. Categorical endpoints will be analyzed using a Cochran Mantel-Haenszel (CMH-row mean scores difference), chi-squared test or Logistic regression models (as appropriate).
    Exploratory/ Candidate Efficacy variables
    • CSF-Biomarkers (tau, ptau, Aβ40, Aβ42, AchE activity)
    • Regional brain glucose metabolism (18FDG-PET)
    • NTB:
    o Digit Span Test
    o Category Fluency Test
    o COWAT
    o Digit Symbol Substitution Test (DSST)
    • ADAS-cog 13 items
    • SPATIAL ORIENTATION AND LEARNING (Amunet)
    • Geriatric Depression Scale (GDS)
    • Clinical Global Impression Scale – Severity/Improvement (CGI-I/CGI-S)
    Todas las variables de eficacia exploratoria se analizarán en el punto final (visita final). Los análisis incluirán el cambio desde la línea de base en el resumen compuesto de NTB Z puntuación calculada después de 6 meses (26 semanas) de tratamiento. Esto implicará un modelo de Análisis de Varianza de Covarianza (ANCOVA) que incorpore el puntaje de referencia y el país como covariables.

    Los análisis adicionales incluirán la evaluación del tiempo de respuesta del tratamiento durante el período de tratamiento, utilizando un modelo mixto de medidas repetidas Análisis de Covarianza (ANCOVA) para la evaluación. Las variables de 18F-Pet Scan serán analizadas de forma descriptiva y exploratoria. Los criterios de valoración categóricos se analizarán utilizando una Cochran Mantel-Haenszel (diferencia de puntuación media de la fila CMH), prueba de ji cuadrado o modelos de regresión logística (según corresponda).
    Variables de Eficacia Exploratoria / Candidata
    • biomarcadores CSF (tau, ptau, Aβ40, Aβ42, actividad AchE)
    • El metabolismo regional de la glucosa cerebral (18FDG-PET)
    • NTB:
    O Prueba de escala de dígitos
    O Categoría Fluency Test
    COWAT
    O Prueba de sustitución de símbolos de dígitos (DSST)
    • ADAS-cog 13 artículos
    • ORIENTACIÓN Y APRENDIZAJE ESPACIAL (Amunet)
    • Escala de Depresión Geriátrica (GDS)
    • Escala de Impresión Global Clínica - Gravedad / Mejora (CGI-I / CGI-S)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Changes between baseline and end of study visit (26 weeks)
    Cambios entre el inicio y el final de la visita de estudio (26 semanas)
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    LM11A-31-BHS (Diferentes dosis)
    LM11A-31-BHS (differnt dose)
    E.8.2.4Number of treatment arms in the trial3
    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.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA12
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial 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
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months8
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 40
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 80
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state40
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 120
    F.4.2.2In the whole clinical trial 120
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-08-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-07-26
    P. End of Trial
    P.End of Trial StatusOngoing
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