E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diseases and Related Health Problems, tenth revision (ICD-10) and with a Childhood Autism Rating Scale (CARS) score > 34. |
Niños y adolescentes (varones y mujeres) de ≥2 a ≤18 años de edad que pesan ≥11 kg, correspondiente a F84.0 (Autismo Infantil) o F84.5 (Síndrome de Asperger) de acuerdo a la Clasificación Estadística Internacional sobre Enfermedades y Problemas de Salud Relacionados, décima revisión (International Statistical Classification of Diseases and Related Health Problems, Tenth revision - ICD-10) y con una puntuación CARS > 34. |
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E.1.1.1 | Medical condition in easily understood language |
Autism and/or Asperger's Syndrome |
Autismo Infantil/Síndrome de Asperger |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Behaviours [F01] |
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 determine the optimal dose strength for the pivotal Phase III study |
Niños y adolescentes con TEA confirmada según orientaciones internacionales. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the pharmacokinetics (PK) of Bumetanide in children and adolescents with ASD;
To confirm the efficacy of Bumetanide in the treatment of children and adolescents with autistic spectrum Disorder (ASD).
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Evaluar la farmacocinética (PK) de bumetanida en niños y adolescentes con trastorno del espectro del autismo (TEA);
Confirmar la eficacia de bumetanida en el tratamiento de niños y adolescentes con TEA. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male or female patients aged 2 to 18 years, inclusive;
2.F84.0 (Childhood Autism) or F84.5 (Asperger's Syndrome) scores according to the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10);
3.Patients meeting criteria for autism on Autism Diagnosis Interview-Revised (ADI-R).
4.CARS score > 34 points;
5.Weight ≥11 kg;
6. The patient is able to comply with the protocol for the duration of the study, including treatment, blood sampling and scheduled follow-up visits and examinations;
7.The patient's parent/guardian has given written informed consent, prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care. |
1. Varones o mujeres de ≥2 años a ≤18 años;
2. Puntuaciones de F84.0 (Autismo infantil) o F84.5 (Síndrome de Asperger), según la ICD 10;
3. Cumplir con los criterios de autismo de la Escala de Observación Diagnóstica del Autismo - Genérica (ADOS G) y ADI-R (si está disponible la ADI R retrospectiva para niños >5 años de edad, no es necesario repetir la evaluación ADI R);
4. Puntuación CARS >34 puntos;
5. Peso ≥11 kg;
6. Capacidad para cumplir con los procedimientos especificados en el protocolo durante todo el estudio, incluyendo tratamiento, toma de muestras, y visitas y exámenes de seguimiento planificados;
7. Consentimiento informado por escrito (y aceptado, si corresponde según las leyes y regulaciones locales), antes de cualquier procedimiento relacionado con el estudio y que no sea parte de los cuidados médicos normales, en el entendimiento de que el consentimiento puede ser retirado por el paciente en cualquier momento, sin perjudicar su atención médica futura.
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E.4 | Principal exclusion criteria |
1.Serious, unstable illnesses including, gastroenterologic, respiratory, cardiovascular (QT interval lengthening), endocrinologic, immunologic, or hematologic disease;
2.Renal or hepatic dysfunction that would interfere with excretion or metabolism of Bumetanide;
3.Patients with any specific neurological disorders like seizures, microcephaly;
4.Patients taking psychoactive medications except melatonin;
5.Documented history of hypersensitivity reaction to sulfonamide derivatives. |
1. Enfermedad grave e inestable, incluyendo enfermedades gastroenterológicas, respiratoratorias, cardiovasculares (alargamiento del intervalo QT), endocrinológicas, inmunológicas o hematológicas;
2. Disfunción renal o hepática que pueda interferir con la excreción o el metabolismo de bumetanida;
3. Trastornos neurológicos tales como convulsiones y microcefalia;
4. Tratamiento con medicamentos psicoactivos, excepto melatonina;
5. Historia documentada de reacción de hipersensibilidad a los derivados de la sulfamida.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in CARS from baseline (Day 1) to Day 90.
The treatment groups will be compared using a non-parametric test as specified in the Statistical Analysis Plan.
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Cambio en la CARS desde el valor inicial (Día 1) al Día 90.
Los grupos de tratamiento serán comparados utilizando una prueba no paramétrica, tal como se especifica en el SAP. |
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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) |
By way of further confirmatory measures of efficacy, the following endpoints will be analyzed:
- CGI-I scale;
- The Vineland Adaptive Behavior Scales (Vineland-II) (personal and social skills);
- The Social Responsiveness Scale (SRS) (focuses on the child?s reciprocal social interactions);
- QOL
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Utilizando mediciones de confirmación adicionales de eficacia, se analizarán los siguientes objetivos finales:
• CGI-I;
• Escalas de Comportamiento Adaptativo de Vineland (Vineland-II);
• SRS (enfocada en las interacciones sociales recíprocas del niño);
• QoL.
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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 | 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 | Yes |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |