Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
- Conditions
- Autism Spectrum Disorder (ASD)
- Interventions
- Drug: Bumetanide Oral SolutionDrug: Placebo
- Registration Number
- NCT03715166
- Lead Sponsor
- Institut de Recherches Internationales Servier
- Brief Summary
The purpose of this study was to evaluate the efficacy and the safety of bumetanide/S95008 in the improvement of Autism Spectrum Disorder core symptoms.
- Detailed Description
The present study (CL3-95008-001) was performed in children and adolescents from 7 to less than 18 years old presenting with ASD. A 6-month double-blind treatment period was performed in which efficacy and safety of bumetanide 0.5mg BID were assessed versus placebo. This double-blind period was followed by a 6-month open label treatment period of bumetanide 0.5mg BID in which long term safety was evaluated.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 211
- Male and female patients from 7 to less than 18 years
- Out patients
- Primary diagnosis of ASD as per Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (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
- 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
- Severe electrolyte imbalance that is likely to interfere with the study conduct or evaluation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Bumetanide/S95008 Bumetanide Oral Solution - Placebo Placebo -
- Primary Outcome Measures
Name Time Method Childhood Autism Rating Scale, Second Edition (CARS2) total raw score Change from baseline to 6 month Efficacy criterion The CARS2 is a 15 item rated instrument. The rating values given for the 15 areas are summed to produce a Total score.
- Secondary Outcome Measures
Name Time Method Vineland Adaptative Behaviour Sales, Second Edition (VABS II) subscores Change from baseline to 6 month Efficacy criterion Scale designated to measure adaptative behaviour
Adverse events and Paediatric Adverse Event Rating Scale (PAERS) On average of 52 weeks Safety criterion Inventory report used to identify signs/symptoms experienced by the patient since the study treatment initiation.
Social Responsiveness Scale, Second Edition (SRS-2) total raw score Change from baseline to 6 month Efficacy criterion 65 items scale measuring symptoms associated with autism
Clinical Global Impression - Global Improvement (CGI-I) score At 6 months Efficacy criterion Scale which assesses the severity of the illness and the global improvement of the patient under study treatment
Abnormalities in 12-leads electrocardiogram (ECG) parameters selection visit/Week004/Week008/Week012/Week 026/Week030/Week034/Week038/Week052 Safety criterion
Renal ultrasound selection visit/Week026/Week052 Safety criterion Assessment of the renal function
the Columbia Suicide Severity Rating Scale Children's version (C-SSRS-C) Week000/Week012/Week026/Week038/Week052 Scale which assesses suicidal ideation and suicidal behaviour
Tanner stage Week000/Week026/Week052 Safety criterion Assessment of Pubertal development
Acceptability and palatability questionnaire Week026 Acceptability and palatability criterion Assessment of the ease of use to use the dosing device
Paediatric Quality of Life Inventory (PedsQL) questionnaire Week000/Week004/Week012/Week026/Week030/Week038/Week052 Quality of Life criterion Assessment of parent/legal representative perception of patient health related quality of life
Trial Locations
- Locations (45)
Clinica di Neuropsichiatria dell'Infanzia e dell'Adolescenza Ospedale Pediatrico-Microcitemico
🇮🇹Cagliari, Sardegna, Italy
Programma Interdipartimentale "Autismo 0-90" A.O.U. Policlinico "Gaetano Martino"
🇮🇹Messina, Sicilia, Italy
U.O. di Neuropsichiatria Infantile Azienda Ospedaliera Universitaria Senese
🇮🇹Siena, Toscana, Italy
Bekes Megyei Kozponti Korhaz Gyermek es ifjusagpszichiatriai osztaly
🇭🇺Gyula, Hungary
Klinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters am Zentralinstitut für Seelische Gesundheit
🇩🇪Mannheim, Baden-Württemberg, Germany
Vadaskert Korhaz es Szakambulancia
🇭🇺Budapest, Hungary
Servus Salvus Kft.
🇭🇺Budapest, Hungary
Universitätsklinikum Carl Gustav Carus an der TU Dresden, Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und
🇩🇪Dresden, Saxony (Sachsen), Germany
Szegedi Tudományegyetem Szent-Gyorgy Albert Klinikai Kozpont Gyermekgyógyászati Klinika Gyermek es Ifjusagpszichiátriai o
🇭🇺Szeged, Hungary
Accare Groningen
🇳🇱Groningen, Netherlands
NAVICULA Centrum Diagnozy i Terapii Autyzmu w Łodzi
🇵🇱Lodz, Wojewodztwo Lodzkie, Poland
Samodzielny Publiczny Dziecięcy Szpital Kliniczny w Warszawie Oddział Kliniczny Psychiatrii Wieku Rozwojowego
🇵🇱Warszawa, Wojewodztwo Mazowieckie, Poland
Unità Semplice di Psichiatria Infantile Policlinico Universitario di Napoli - Università Federico II
🇮🇹Napoli, Campania, Italy
Neuro Riabilitazione/Psicopatologia dell'età evolutiva Istituto Scientifico Medea - Bosisio Parini
🇮🇹Bosisio Parini, Lombardia, Italy
U.O. di Neuropsichiatria Infantile Fondazione Istituto Neurologico Nazionale Casimiro Mondino Istituto di Ricovero e Cura a Carattere Scientifico
🇮🇹Pavia, Lombardia, Italy
Niepubliczny Zakład Opieki Zdrowotnej Gdańskie Centrum Zdrowia Sp. z o.o.
🇵🇱Gdansk, Wojewodztwo Pomorskie, Poland
Centrum Badań Klinicznych PI-House sp. z o.o
🇵🇱Gdansk, Poland
Fundacja SYNAPSIS ul.
🇵🇱Warszawa, Poland
Hospital Puerta de Hierro
🇪🇸Majadahonda, Madrid, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Niño Jesus
🇪🇸Madrid, Spain
ReCognition Health
🇬🇧London, United Kingdom
The Winnicott Centre
🇬🇧Manchester, United Kingdom
Policlinica Guipuzcoa
🇪🇸San Sebastian, Guipuzcoa, Spain
Hospital Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital General Universitario de Alicante
🇪🇸Alicante, Spain
Hospital Universitário Walter Cantídio - Universidade Federal do Ceará
🇧🇷Fortaleza, Brazil
Trial Tech em Pesquisas com Medicamentos Ltda
🇧🇷Curitiba, Brazil
Universidade Federal de São Paulo, Escola Paulista de Medicina
🇧🇷São Paulo, Brazil
Hospital São Vicente de Paulo
🇧🇷Passo Fundo, Brazil
GSC CHU-LENVAL Centre ressource autisme
🇫🇷Nice, Alpes-Maritimes, France
Faculdade de Medicina da Universidade de São Paulo - Departamento de Psiquiatria
🇧🇷São Paulo, Brazil
Hôpital Le Vinatier CRA Rhône-Alpes, Bat 211
🇫🇷Bron, Auvergne-Rhône-Alpes, France
Centre d'Investigation Clinique de Lyon
🇫🇷Bron, Auvergne Rhone Alpes, France
Hôpitaux Universitaires de Strasbourg Service de Psychiatrie de l'Enfant et de l'Adolescent
🇫🇷Strasbourg, Alsace-Champagne-Ardenne-Lorraine, France
CHU Rouen
🇫🇷Rouen, Normandie, France
Hôpital Robert Debré Service de Psychiatrie de l'enfant et de l'adolescent
🇫🇷Paris, Il De France, France
Hôpital des Enfants-Pellegrin
🇫🇷Bordeaux, Nouvelle Aquitaine, France
Centre Hospitalier Charles Perrens CRA Aquitaine
🇫🇷Bordeaux, Nouvelle-Aquitaine, France
Universitätsklinikum Freiburg, Zentrum für Psychische Erkrankungen, Klinik für Psychiatrie, Psychotherapie und Psychosomatik im Kindes- und Jugendalter
🇩🇪Freiburg, Baden-Württemberg, Germany
U.O.C. Psichiatria dello Sviluppo IRCCS Fondazione Stella Maris
🇮🇹Calambrone, Toscana, Italy
Forward Thinking Birmingham_Birmingham Women's and Children's NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
Hospita Mutua de Terrassa
🇪🇸Terrassa, Barcelona, Spain
Centre Hospitalier du Rouvray Centre de Ressources pour l'Autisme
🇫🇷Sotteville-lès-Rouen, Normandie, France
Centro Hospitalar e Universitario de Coimbra Hospital Pediatrico
🇵🇹Coimbra, Portugal