E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Autism Spectrum Disorder (ASD) |
Trastorno del Espectro Autista |
|
E.1.1.1 | Medical condition in easily understood language |
Autism Spectrum Disorder (ASD) |
Trastorno del Espectro Autista |
|
E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
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 | 10063844 |
E.1.2 | Term | Autism spectrum disorder |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
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 demonstrate the superiority of bumetanide (0.5mg BID) oral liquid formulation compared to placebo in the improvement of ASD core symptoms after 6 months of treatment in ASD children aged from 2 to less than 7 years old |
Demostrar la superioridad de la formulación líquida oral de bumetanida (0,5 mg 2 veces al día) en comparación con placebo en la mejoría de los síntomas principales de TEA después de 6 meses de tratamiento en niños de 2 a menos de 7 años de edad . |
|
E.2.2 | Secondary objectives of the trial |
- To assess the effect of bumetanide on the other efficacy endpoints - To assess the safety of bumetanide - To confirm the acceptability and palatability of the oral liquid formulation - To describe the bumetanide effects on patients quality of life - To improve existing pharmacokinetic model of bumetanide in this population |
-Evaluar el efecto de la bumetanida sobre los criterios secundarios de valoración de la eficacia -Evaluar la seguridad de la bumetanida -Confirmar la aceptabilidad y palatabilidad de la formulación líquida oral -Describir los efectos de la bumetanida sobre la calidad de vida de los pacientes -Mejorar el modelo farmacocinético existente de la bumetanida en esta población |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male and female patients from 2 to less than 7 years - Out patients - Primary diagnosis of ASD as per DSM-5 criteria - Criteria met for ASD on Autism Diagnostic Observation Schedule (ADOS-2) and Autism Diagnosis Interview Revised (ADI-R) - CGI (Clinical Global Impression) – Severity rating Score ≥ 4 - Childhood Autism Rating Scale second edition (CARS2-ST or HF) total raw score ≥ 34 - Social Responsiveness Scale second edition total score (SRS-2 T-Score) ≥ 66 - Absence of known monogenic syndrome (Fragile X, Rett syndrome ...) - Absence of any clinically significant abnormality likely to interfere with the conduct of the study according to the judgment of the investigator |
-Hombres y mujeres de 2 a menos de 7 años de edad -Pacientes ambulatorios -Diagnóstico principal de TEA según los criterios DSM-5 -Cumplir los criterios de TEA según la Escala de Observación para el Diagnóstico del Autismo-2 (ADOS-2) y la Entrevista para el Diagnóstico del Autismo -Revisada (ADI-R) -Puntuación de la gravedad > 4 en la escala de Impresión Clínica Global (CGI) -Puntuación bruta total > 34 en la segunda edición de la Escala de Evaluación del Autismo Infantil (CARS2-ST o HF) -Puntuación total > 66T en la segunda edición de la Escala de Respuesta Social (SRS-2) -Ausencia de diagnóstico de síndrome del cromosoma X frágil o de Rett -Ausencia de cualquier anomalía de importancia clínica que pueda interferir en la realización del estudio a criterio del investigador. |
|
E.4 | Principal exclusion criteria |
- Patients not able to follow the study assessments defined by the protocol, with the exception of self-rating questionnaires which will be assessed by parent/legal representative/caregiver for those patients unable to complete them - Patients having a high suicidal risk according to the investigator judgement - Chronic renal dysfunction - Chronic cardiac dysfunction - Patient with unstable psychotherapy, behavioural, cognitive or cognitive-behavioural therapy - Absence of electrolyte imbalance that is likely to interfere with the study conduct or evaluation |
-Pacientes no capaces de cumplir con las evaluaciones de seguimiento previstas en el protocolo a excepción de los cuestionarios que pueden ser completados por los padres/representantes legales/cuidadores para los pacientes que no sean capaces de hacerlo por sí mismos -Pacientes con alto riesgo de suicidio a juicio del investigador -Disfunción renal crónica -Disfunción cardiaca crónica -Paciente con terapias cognitivas, de comportamiento, mixtas o psicoterapia inestables -Desequilibrio electrolítico severo que pueda interferir con el desarrollo o evaluación del estudio |
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E.5 End points |
E.5.1 | Primary end point(s) |
CARS2 total raw score |
puntuación bruta total de CARS2 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Change from baseline to 6 month |
Cambio de basal a mes 6 |
|
E.5.2 | Secondary end point(s) |
- Each individual CARS2 domain, SRS-2 total raw score, CGI-I score, VABS II subscores - Adverse events, Paediatric Adverse Event Rating Scale (PAERS), clinical laboratory evaluation, vital signs and clinical examination, electrocardiogram, renal ultrasound, Columbia Suicide Severity Rating Scale Children's version (C-SSRS-C) - Acceptability and palatability questionnaire - Paediatric Quality of Life Inventory (PedsQL), WHOQOL-Bref questionnaire - PK parameters of bumetanide |
-Variación en cada dominio individual de CARS2, puntuación bruta total de SRS-2, puntuación de CGI-I, VABS II -Acontecimientos adversos, Escala de Puntuación de Acontecimientos Adversos Pediátricos (PAERS), evaluación del laboratorio clínico, constantes vitales y exploración clínica, electrocardiograma, ecografía renal, escala Columbia para evaluar -Evaluaciones de la aceptabilidad y palatabilidad -Inventario de Calidad de Vida Pediátrico (PedsQL), cuestionario WHOQOL-Bref -Parámetros farmacocinéticos de bumetanida |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
SRS-2 total raw score: W000/W004/W012/W026/W038/W052 CGI-I score: W000+Day17/W004/W008/W012/W016/W020/W026/W038/W052/WEND VABS II subscores: W000/W026/W052 Each individual CARS2 domain: W000/W004/W012/W026/W038/W052/WEND Adverse events/PAERS/Clinical laboratory evaluation/Electrolytes monitoring (sodium, potassium)/Clinical examination: all along the study Vital signs: ASSE/W000/W00+D17/W012/W026/W026+Day17/W038/W052 Electrocardiogram: ASSE/W004/W008/W012, W026/W030/W034/W038/W052 Renal ultrasound: ASSE/W026/W052 C-SSRS-C: W000/W012/W026/W038/W052 Acceptability and palatability questionnaire: W026 PedsQL / WHOQOL-Bref questionnaire: W000/W004/W012/W026/W030/W038/W052 + W008/W034 for WHOQOL-Bref questionnaire PK parameters of bumetanide: W012/W026 |
Puntuación bruta total SRS-2: W000/W004/W012/W026/W038/W052 Puntuación CGI-I: W000+Day17/W004/W008/W012/W016/W020/W026/W038/W052/WEND Sub puntuaciones VABS II: W000/W026/W052 Cada dominio individual CARS2 : W000/W004/W012/W026/W038/W052/WEND Acontecimientos adversos/PAERS/evaluación de laboratorio/monitorización electrolitos (sodio, potasio)/exploración clínica: durante todo el estudio Signos vitales: ASSE/W000/W000+Day17/W012/W026/W026+Day17/W038/W052 Electrocardiograma: ASSE/W004/W008/W012/W026/W030/W034/W038/W052 Ecografía renal :ASSE/W026/W052 C-SSRS-C: W000/W012/W026/W038/W052 Cuestionario de aceptabilidad y palatabilidad: W026 Cuestionarios PedsQL / WHOQOL-Bref: W000/W004/W012/W026/W030/W038/W052 + W008/W034 fpara el cuestionario WHOQOL-Bref PK: W012/W026 |
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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 | 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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
Double-blind treatment period of 6 months followed by an open-label treatment period of 6 months |
|
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
| 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 | 50 |
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 | 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
|
Last Visit Last Participant as stated in the protocol |
última visita del último paciente como indicado en el protocolo |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |