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

NCT03715166 | Terminated Phase 3 DMC

• 2 other identifiers: CL3-95008-0012017-004419-38
• Study Type: interventional
• Target: 211
• Locations: 10 countries
• Sites: 45

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.

Conditions

Autism Spectrum Disorder (ASD)

Outcome Measures

Primary Outcomes (1)

• Childhood Autism Rating Scale, Second Edition (CARS2) total raw score

  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.

  Change from baseline to 6 month

Secondary Outcomes (10)

• Social Responsiveness Scale, Second Edition (SRS-2) total raw score

  Change from baseline to 6 month

• Clinical Global Impression - Global Improvement (CGI-I) score

  At 6 months

• Vineland Adaptative Behaviour Sales, Second Edition (VABS II) subscores

  Change from baseline to 6 month

• Adverse events and Paediatric Adverse Event Rating Scale (PAERS)

  On average of 52 weeks

• Abnormalities in 12-leads electrocardiogram (ECG) parameters

  selection visit/Week004/Week008/Week012/Week 026/Week030/Week034/Week038/Week052

Study Arms (2)

Bumetanide/S95008

EXPERIMENTAL

Drug: Bumetanide Oral Solution

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Bumetanide Oral Solution DRUG

Oral Solution dosed at 0.5mg/mL Taken twice daily

Bumetanide/S95008

Placebo DRUG

Oral Solution Taken twice daily

Placebo

Eligibility Criteria

• Age: 7 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Institut de Recherches Internationales Servier: lead
• ADIR, a Servier Group company: collaborator

Study Sites (45)

Trial Tech em Pesquisas com Medicamentos Ltda

Curitiba, 80240-280, Brazil

Location

Hospital Universitário Walter Cantídio - Universidade Federal do Ceará

Fortaleza, 60430-370, Brazil

Location

Hospital São Vicente de Paulo

Passo Fundo, 99010-080, Brazil

Location

Universidade Federal de São Paulo, Escola Paulista de Medicina

São Paulo, 04017-030, Brazil

Location

Faculdade de Medicina da Universidade de São Paulo - Departamento de Psiquiatria

São Paulo, 054030-010, Brazil

Location

GSC CHU-LENVAL Centre ressource autisme

Nice, Alpes-Maritimes, 6200, France

Location

Centre d'Investigation Clinique de Lyon

Bron, Auvergne-Rhône-Alpes, 69677, France

Location

Hôpital Le Vinatier CRA Rhône-Alpes, Bat 211

Bron, Auvergne-Rhône-Alpes, 69678, France

Location

Hôpitaux Universitaires de Strasbourg Service de Psychiatrie de l'Enfant et de l'Adolescent

Strasbourg, Grand Est, 67091, France

Location

Hôpital Robert Debré Service de Psychiatrie de l'enfant et de l'adolescent

Paris, Il de France, 75019, France

Location

CHU Rouen

Rouen, Normandy, 76000, France

Location

Centre Hospitalier du Rouvray Centre de Ressources pour l'Autisme

Sotteville-lès-Rouen, Normandy, 76301, France

Location

Centre Hospitalier Charles Perrens CRA Aquitaine

Bordeaux, Nouvelle-Aquitaine, 33076, France

Location

Hôpital des Enfants-Pellegrin

Bordeaux, Nouvelle-Aquitaine, 33076, France

Location

Universitätsklinikum Freiburg, Zentrum für Psychische Erkrankungen, Klinik für Psychiatrie, Psychotherapie und Psychosomatik im Kindes- und Jugendalter

Freiburg im Breisgau, Baden-Wurttemberg, 79104, Germany

Location

Klinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters am Zentralinstitut für Seelische Gesundheit

Mannheim, Baden-Wurttemberg, 68159, Germany

Location

Universitätsklinikum Carl Gustav Carus an der TU Dresden, Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und

Dresden, Saxony (Sachsen), 01307, Germany

Location

Vadaskert Korhaz es Szakambulancia

Budapest, 1021, Hungary

Location

Servus Salvus Kft.

Budapest, 1026, Hungary

Location

Bekes Megyei Kozponti Korhaz Gyermek es ifjusagpszichiatriai osztaly

Gyula, 5700, Hungary

Location

Szegedi Tudományegyetem Szent-Gyorgy Albert Klinikai Kozpont Gyermekgyógyászati Klinika Gyermek es Ifjusagpszichiátriai o

Szeged, 6725, Hungary

Location

Unità Semplice di Psichiatria Infantile Policlinico Universitario di Napoli - Università Federico II

Napoli, Campania, 80131, Italy

Location

Neuro Riabilitazione/Psicopatologia dell'età evolutiva Istituto Scientifico Medea - Bosisio Parini

Bosisio Parini, Lombardy, 23842, Italy

Location

U.O. di Neuropsichiatria Infantile Fondazione Istituto Neurologico Nazionale Casimiro Mondino Istituto di Ricovero e Cura a Carattere Scientifico

Pavia, Lombardy, 27100, Italy

Location

Clinica di Neuropsichiatria dell'Infanzia e dell'Adolescenza Ospedale Pediatrico-Microcitemico

Cagliari, Sardinia, 09131, Italy

Location

Programma Interdipartimentale "Autismo 0-90" A.O.U. Policlinico "Gaetano Martino"

Messina, Sicily, 98125, Italy

Location

U.O.C. Psichiatria dello Sviluppo IRCCS Fondazione Stella Maris

Calambrone, Tuscany, 56128, Italy

Location

U.O. di Neuropsichiatria Infantile Azienda Ospedaliera Universitaria Senese

Siena, Tuscany, 53100, Italy

Location

Accare Groningen

Groningen, 9713 GZ, Netherlands

Location

Samodzielny Publiczny Dziecięcy Szpital Kliniczny w Warszawie Oddział Kliniczny Psychiatrii Wieku Rozwojowego

Warsaw, Masovian Voivodeship, 02-091, Poland

Location

Niepubliczny Zakład Opieki Zdrowotnej Gdańskie Centrum Zdrowia Sp. z o.o.

Gdansk, Pomeranian Voivodeship, 80-542, Poland

Location

Centrum Badań Klinicznych PI-House sp. z o.o

Gdansk, 80-546, Poland

Location

Fundacja SYNAPSIS ul.

Warsaw, 02-085, Poland

Location

NAVICULA Centrum Diagnozy i Terapii Autyzmu w Łodzi

Lodz, Łódź Voivodeship, 91-129, Poland

Location

Centro Hospitalar e Universitario de Coimbra Hospital Pediatrico

Coimbra, 300-062, Portugal

Location

Hospita Mutua de Terrassa

Terrassa, Barcelona, 08221, Spain

Location

Policlinica Guipuzcoa

Donostia / San Sebastian, Guipuzcoa, 20014, Spain

Location

Hospital Puerta de Hierro

Majadahonda, Madrid, 28222, Spain

Location

Hospital General Universitario de Alicante

Alicante, 03007, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Niño Jesus

Madrid, 28009, Spain

Location

Hospital Universitario Gregorio Marañon

Madrid, 28009, Spain

Location

Forward Thinking Birmingham_Birmingham Women's and Children's NHS Foundation Trust

Birmingham, B4 6NH, United Kingdom

Location

ReCognition Health

London, W1G 9JF, United Kingdom

Location

The Winnicott Centre

Manchester, M13 0JE, United Kingdom

Location

Related Publications (2)

• Fuentes J, Parellada M, Georgoula C, Oliveira G, Marret S, Crutel V, Albarran C, Lambert E, Penelaud PF, Ravel D, Ben Ari Y. Bumetanide oral solution for the treatment of children and adolescents with autism spectrum disorder: Results from two randomized phase III studies. Autism Res. 2023 Oct;16(10):2021-2034. doi: 10.1002/aur.3005. Epub 2023 Oct 4.

  PMID: 37794745 BACKGROUND

• Hawken N, Falissard B, Choquet C, Francois C, Tardu J, Schmid R. Exit interviews from two randomised placebo-controlled phase 3 studies with caregivers of young children with autism spectrum disorder. Front Child Adolesc Psychiatry. 2024 Jun 5;3:1236340. doi: 10.3389/frcha.2024.1236340. eCollection 2024.

  PMID: 39816573 DERIVED

MeSH Terms

Conditions

Autism Spectrum Disorder

Interventions

Bumetanide

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; meta-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 6-month, randomized, double-blind, placebo-controlled, parallel groups followed by an open label active 6-month treatment period with bumetanide.

Study Record Dates

• First Submitted: October 12, 2018
• First Posted: October 23, 2018
• Study Start: September 24, 2018
• Primary Completion: September 13, 2021
• Study Completion: September 13, 2021
• Last Updated: July 25, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
• Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.

Locations

PL (5); FR (9); NL (1); BR (5); DE (3); IT (7); GB (3); ES (7); HU (4); PT (1)