Clinical trial NCT03715153: Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
Official title: Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder. A 6-month Randomised, Double-blind, Placebo Controlled Multicentre Parallel Group Study to Evaluate Efficacy and Safety of Bumetanide 0.5mg Twice a Day Followed by an Open Label Active 6-month Treatment Period With Bumetanide (0.5mg Twice a Day) and a 6 Weeks Discontinuation Period After Treatment Stop.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Autism Spectrum Disorder (ASD)
Lead sponsor: Servier
Sponsor class: INDUSTRY
Collaborators: name: ADIR, a Servier Group company
First posted: 2018-10-23
Enrollment: 211
Sex: ALL
Minimum age (years): 2
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 6-month, randomized, double-blind, placebo-controlled, parallel groups followed by an open label active 6-month treatment period with bumetanide.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

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
* Severe electrolyte imbalance that is likely to interfere with the study conduct or evaluation

Primary outcomes:
measure: Childhood Autism Rating Scale, Second Edition (CARS2) Total Raw Score
timeFrame: Change from baseline to Week 26
Secondary outcomes:
measure: Social Responsiveness Scale, Second Edition (SRS-2) Total Raw Score
timeFrame: Change from baseline to Week 26
measure: Clinical Global Impression - Global Improvement (CGI-I) Score
timeFrame: At Week 26
measure: Vineland Adaptative Behaviour Scale II (VABS II)
timeFrame: Change from baseline to Week 26
measure: Number of Patients With Abnormalities in 12-leads Electrocardiogram (ECG) Parameters
timeFrame: Week 26
measure: Columbia-Suicide Severity Scale Children's Version (C-SSRS-C)
timeFrame: Week 26
measure: Acceptability and Palatability Questionnaires - Only Descriptive Analyses
timeFrame: Week 26
measure: Paediatric Quality of Life Inventory (PedsQL) Questionnaire
timeFrame: Change from baseline to week 26
measure: Number of Participants Experiencing at Least 1 Treatment Emergent Adverse Event (TEAE)
timeFrame: through week 52
Other outcomes:
Locations:
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: Liverpool
country: Australia
facility: Liverpool Hospital
city: Parkville
country: Australia
facility: The Royal Children's Hospital Melbourne
city: Curitiba
country: Brazil
facility: Trial Tech em Pesquisas com Medicamentos Ltda
city: Fortaleza
country: Brazil
facility: Hospital Universitário Walter Cantídio-Universidade Federal do Ceará
city: Joinville
country: Brazil
facility: Clínica Neurológica e Neurocirúrgica de Joinville
city: Passo Fundo
country: Brazil
facility: Hospital São Vicente de Paulo
city: São Paulo
country: Brazil
facility: Universidade Federal de São Paulo, Escola Paulista de Medicina
city: São Paulo
country: Brazil
facility: Faculdade de Medicina da Universidade de São Paulo - Departamento de psiquiatra
city: Poruba
country: Czechia
facility: University hospital of Ostrava, Department of Psychiatry
state: Ostrava
city: Brno
country: Czechia
facility: University Hospital Brno, Department of Child Neurology
city: Praha
country: Czechia
facility: Institute of Neuropsychiatric Care, Department of Child Psychiatry
city: Nice
country: France
facility: GSC CHU-LENVAL Centre ressource autisme
state: Alpes-Maritimes
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg Service de Psychiatrie de l'Enfant et de l'Adolescent
state: Alsace-Champagne-Ardenne-Lorraine
city: Bron
country: France
facility: Centre d'Investigation Clinique de Lyon
state: Auvergne Rhone Alpes
city: Bron Cedex
country: France
facility: Hôpital Le Vinatier CRA Rhône-Alpes, Bat 211
state: Auvergne-Rhône-Alpes
city: Paris
country: France
facility: Hôpital Robert Debré Service de Psychiatrie de l'enfant et de l'adolescent
state: Ile De France
city: Rouen
country: France
facility: CHU Rouen
state: Normandie
city: Sotteville-lès-Rouen
country: France
facility: Centre Hospitalier du Rouvray Centre de Ressources pour l'Autisme
state: Normandie
city: Bordeaux
country: France
facility: Hôpital des Enfants-Pellegrin
state: Nouvelle Aquitaine
city: Bordeaux
country: France
facility: Centre Hospitalier Charles Perrens CRA Aquitaine
state: Nouvelle-Aquitaine
city: Budapest
country: Hungary
facility: Vadaskert Korhaz es Szakambulancia
city: Budapest
country: Hungary
facility: Servus Salvus Kft.
city: Budapest
country: Hungary
facility: Magyar Református Egyház Bethesda Gyermekkórháza
city: Gyula
country: Hungary
facility: Bekes Megyei Kozponti Korhaz Gyermek es ifjusagpszichiatriai osztaly
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem Szent-Gyorgy Albert Klinikai Kozpont Gyermekgyógyászati Klinika Gyermek es Ifjusagpszichiátriai o
city: Bosisio Parini
country: Italy
facility: Neuro Riabilitazione/Psicopatologia dell'età evolutiva Istituto Scientifico Medea - Bosisio Parini
state: Lombardia
city: Pavia
country: Italy
facility: U.O. di Neuropsichiatria Infantile Fondazione Istituto Neurologico Nazionale Casimiro Mondino Istituto di Ricovero e Cura a Carattere Scientifico
state: Lombardia
city: Cagliari
country: Italy
facility: Clinica di Neuropsichiatria dell'Infanzia e dell'Adolescenza Ospedale Pediatrico-Microcitemico
state: Sardegna
city: Messina
country: Italy
facility: Programma Interdipartimentale "Autismo 0-90" A.O.U. Policlinico "Gaetano Martino"
state: Sicilia
city: Calambrone
country: Italy
facility: U.O.C. Psichiatria dello Sviluppo IRCCS Fondazione Stella Maris
state: Toscana
city: Siena
country: Italy
facility: U.O. di Neuropsichiatria Infantile Azienda Ospedaliera Universitaria Senese
state: Toscana
city: Gdansk
country: Poland
facility: "Niepubliczny Zakład Opieki Zdrowotnej Gdańskie Centrum Zdrowia Sp. z o.o.
city: Gdansk
country: Poland
facility: Centrum Badań Klinicznych PI-House sp. z o.o
city: Lodz
country: Poland
facility: NAVICULA Centrum Diagnozy i Terapii Autyzmu w Łodzi
city: Warszawa
country: Poland
facility: Fundacja SYNAPSIS ul.
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Dziecięcy Szpital Kliniczny w Warszawie Oddział Kliniczny Psychiatrii Wieku Rozwojowego
city: Coimbra
country: Portugal
facility: Centro Hospitalar e Universitario de Coimbra Hospital Pediatrico
city: Bratislava
country: Slovakia
facility: National Institute of Children Diseases, Department of Child Psychiatry
city: Košice
country: Slovakia
facility: EPAMED, s.r.o.
city: Terrassa
country: Spain
facility: Hospita Mutua de Terrassa
state: Barcelona
city: San Sebastian
country: Spain
facility: Policlinica Guipuzcoa
state: Guipuzcoa
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro
state: Madrid
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Niño Jesus
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Marañon
city: Colchester
country: United Kingdom
facility: Colchester Hospital
city: London
country: United Kingdom
facility: ReCognition Health
city: Manchester
country: United Kingdom
facility: The Winnicott Centre 195-197 Hathersage Road
Study officials:
References: