Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
- Conditions
- Autism Spectrum Disorder (ASD)
- Interventions
- Drug: BUMETANIDE (S95008) for week 0 - 26Drug: PLACEBO for week 0 - 26Drug: Open-Label BUMETANIDE (S95008) for weeks 26 - 52
- Registration Number
- NCT03715153
- Lead Sponsor
- Institut de Recherches Internationales Servier
- Brief Summary
The purpose of this study was to evaluate the efficacity and the safety of bumetanide/S95008 in the improvement of Autism Spectrum Disorder core symptoms.
- Detailed Description
The present study (CL3-95008-002) was performed in children from 2 to less than 7 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 twice daily in which long term safety was evaluated.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 211
- Male and female patients from 2 to less than 7
- 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-Generic (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 (SRS-2) total score ≥ 66 T-Score
- Absence of diagnosis of Fragile X or 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) followed by Open-Label S95008 BUMETANIDE (S95008) for week 0 - 26 Participants will receive S95008 for 6 months, 26 weeks, and then they will begin an open-label 6 month treatment period with S95008. PLACEBO followed by Open-Label S95008 PLACEBO for week 0 - 26 Participants will receive placebo for 6 months, 26 weeks, and then they will begin an open-label 6 month treatment period with S95008. PLACEBO followed by Open-Label S95008 Open-Label BUMETANIDE (S95008) for weeks 26 - 52 Participants will receive placebo for 6 months, 26 weeks, and then they will begin an open-label 6 month treatment period with S95008. BUMETANIDE (S95008) followed by Open-Label S95008 Open-Label BUMETANIDE (S95008) for weeks 26 - 52 Participants will receive S95008 for 6 months, 26 weeks, and then they will begin an open-label 6 month treatment period with S95008.
- Primary Outcome Measures
Name Time Method Childhood Autism Rating Scale, Second Edition (CARS2) Total Raw Score Change from baseline to Week 26 The CARS2 total raw score range from 15 to 60. This scale is a behaviour rating scale intended to diagnose autism. A total score of 15 indicates that an individual behaviour is within normal limits, whereas a value of 60 indicates that the individual's behaviour is severly abnormal.
In term of change from baseline, the greater the mean value decreases, the better it is.
- Secondary Outcome Measures
Name Time Method Clinical Global Impression - Global Improvement (CGI-I) Score At Week 26 Scale which assesses the severity of the illness and the global improvement of the patient under study treatment.
It ranges from 1 (normal) through to 7 (amongst the most severely ill patients).Number of Patients With Abnormalities in 12-leads Electrocardiogram (ECG) Parameters Week 26 Number of patients with clinically significant ECG abnormalities
The 12-lead electrocardiogram (ECG) is a medical test that is recorded using leads, or nodes, attached to the body. Electrocardiograms (ECGs), capture the electrical activity of the heart and transfer it to graphed paper where abnormalities are reported and interpretated by the cardiologist.Number of Participants Experiencing at Least 1 Treatment Emergent Adverse Event (TEAE) through week 52 Vineland Adaptative Behaviour Scale II (VABS II) Change from baseline to Week 26 Scale designated to measure adaptative behaviour The scale for behaviour ranges from 1 to 67. The more the score decreases, the better it is.
Acceptability and Palatability Questionnaires - Only Descriptive Analyses Week 26 Acceptability and palatability criterion Based on your child's reactions (indirect rating), do you think that he/she found the administration method to be
Social Responsiveness Scale, Second Edition (SRS-2) Total Raw Score Change from baseline to Week 26 The SRS-2 total raw score serves as an index of severity of social deficits in the autism spectrum.
The total raw score ranges from 65 to 260. A value of 65 represents no symptoms disorders, a value of 260 represents a severe autism spectrum disorder.
In terms of change from baseline, the greater the mean value decreases, the better it is.Columbia-Suicide Severity Scale Children's Version (C-SSRS-C) Week 26 Number of patients with suicidal ideation or suicidal behavior. The scale is 0 to 5 with the highest suicidal behavior being a 5 and the absence of suicidal behavior or very minor behaviors are 0. However, statistical analysis was done by looking at the number of patients with suicidal behavior or suicidal ideation during their lifetime and during the last 6 months of treatment.
Paediatric Quality of Life Inventory (PedsQL) Questionnaire Change from baseline to week 26 It represents the assessment of parent/legal representative perception of patient health related quality of life The values of the questionnaire range from 0 to 100. Higher scores indicate better HRQOL (Health-Related Quality of Life)
Trial Locations
- Locations (50)
Centre d'Investigation Clinique de Lyon
🇫🇷Bron, Auvergne Rhone Alpes, France
"Niepubliczny Zakład Opieki Zdrowotnej Gdańskie Centrum Zdrowia Sp. z o.o.
🇵🇱Gdansk, Poland
Bekes Megyei Kozponti Korhaz Gyermek es ifjusagpszichiatriai osztaly
🇭🇺Gyula, Hungary
Centrum Badań Klinicznych PI-House sp. z o.o
🇵🇱Gdansk, Poland
University hospital of Ostrava, Department of Psychiatry
🇨🇿Poruba, Ostrava, Czechia
Hospital Universitário Walter Cantídio-Universidade Federal do Ceará
🇧🇷Fortaleza, Brazil
Institute of Neuropsychiatric Care, Department of Child Psychiatry
🇨🇿Praha, Czechia
Trial Tech em Pesquisas com Medicamentos Ltda
🇧🇷Curitiba, Brazil
University Hospital Brno, Department of Child Neurology
🇨🇿Brno, Czechia
Richmond Behavioral Associates
🇺🇸Staten Island, New York, United States
Clínica Neurológica e Neurocirúrgica de Joinville
🇧🇷Joinville, Brazil
Hospital São Vicente de Paulo
🇧🇷Passo Fundo, Brazil
Liverpool Hospital
🇦🇺Liverpool, Australia
The Royal Children's Hospital Melbourne
🇦🇺Parkville, Australia
Hôpital Le Vinatier CRA Rhône-Alpes, Bat 211
🇫🇷Bron Cedex, Auvergne-Rhône-Alpes, France
Centre Hospitalier Charles Perrens CRA Aquitaine
🇫🇷Bordeaux, Nouvelle-Aquitaine, France
CHU Rouen
🇫🇷Rouen, Normandie, France
Neuro Riabilitazione/Psicopatologia dell'età evolutiva Istituto Scientifico Medea - Bosisio Parini
🇮🇹Bosisio Parini, Lombardia, Italy
Centre Hospitalier du Rouvray Centre de Ressources pour l'Autisme
🇫🇷Sotteville-lès-Rouen, Normandie, France
Samodzielny Publiczny Dziecięcy Szpital Kliniczny w Warszawie Oddział Kliniczny Psychiatrii Wieku Rozwojowego
🇵🇱Warszawa, Poland
Centro Hospitalar e Universitario de Coimbra Hospital Pediatrico
🇵🇹Coimbra, Portugal
EPAMED, s.r.o.
🇸🇰Košice, Slovakia
Vadaskert Korhaz es Szakambulancia
🇭🇺Budapest, Hungary
U.O.C. Psichiatria dello Sviluppo IRCCS Fondazione Stella Maris
🇮🇹Calambrone, Toscana, Italy
Colchester Hospital
🇬🇧Colchester, United Kingdom
Hôpital des Enfants-Pellegrin
🇫🇷Bordeaux, Nouvelle Aquitaine, France
Magyar Református Egyház Bethesda Gyermekkórháza
🇭🇺Budapest, Hungary
U.O. di Neuropsichiatria Infantile Fondazione Istituto Neurologico Nazionale Casimiro Mondino Istituto di Ricovero e Cura a Carattere Scientifico
🇮🇹Pavia, Lombardia, Italy
Clinica di Neuropsichiatria dell'Infanzia e dell'Adolescenza Ospedale Pediatrico-Microcitemico
🇮🇹Cagliari, Sardegna, Italy
U.O. di Neuropsichiatria Infantile Azienda Ospedaliera Universitaria Senese
🇮🇹Siena, Toscana, Italy
NAVICULA Centrum Diagnozy i Terapii Autyzmu w Łodzi
🇵🇱Lodz, Poland
Fundacja SYNAPSIS ul.
🇵🇱Warszawa, Poland
Hospital Niño Jesus
🇪🇸Madrid, Spain
National Institute of Children Diseases, Department of Child Psychiatry
🇸🇰Bratislava, Slovakia
ReCognition Health
🇬🇧London, United Kingdom
Universidade Federal de São Paulo, Escola Paulista de Medicina
🇧🇷São Paulo, Brazil
Policlinica Guipuzcoa
🇪🇸San Sebastian, Guipuzcoa, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Servus Salvus Kft.
🇭🇺Budapest, Hungary
Hospita Mutua de Terrassa
🇪🇸Terrassa, Barcelona, Spain
Hospital Puerta de Hierro
🇪🇸Majadahonda, Madrid, Spain
Faculdade de Medicina da Universidade de São Paulo - Departamento de psiquiatra
🇧🇷São Paulo, Brazil
GSC CHU-LENVAL Centre ressource autisme
🇫🇷Nice, Alpes-Maritimes, France
Hôpitaux Universitaires de Strasbourg Service de Psychiatrie de l'Enfant et de l'Adolescent
🇫🇷Strasbourg, Alsace-Champagne-Ardenne-Lorraine, France
Hôpital Robert Debré Service de Psychiatrie de l'enfant et de l'adolescent
🇫🇷Paris, Ile De France, France
Szegedi Tudományegyetem Szent-Gyorgy Albert Klinikai Kozpont Gyermekgyógyászati Klinika Gyermek es Ifjusagpszichiátriai o
🇭🇺Szeged, Hungary
Programma Interdipartimentale "Autismo 0-90" A.O.U. Policlinico "Gaetano Martino"
🇮🇹Messina, Sicilia, Italy
Hospital General Universitario de Alicante
🇪🇸Alicante, Spain
The Winnicott Centre 195-197 Hathersage Road
🇬🇧Manchester, United Kingdom