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Autism Spectrum Disorder (ASD)Phase 3NCT03715166

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

A Phase 3 study testing Bumetanide Oral Solution in people with Autism Spectrum Disorder (ASD), run by Institut de Recherches Internationales Servier at 45 sites in 10 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 7 to 17 years
Conditions the study is for
Autism Spectrum Disorder (ASD)
What is being tested?
Bumetanide Oral Solution
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
211 participants
Where
45 sitesin 10 countries
Study dates
24 Sep 2018to 13 Sep 2021
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 7 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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
Show all 9Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

45 sites in 10 countries.

45 sites in 10 countries

France9 sites

  • Centre Hospitalier Charles Perrens CRA Aquitaine

    Bordeaux, New Aquitaine, 33076

  • Hôpital des Enfants-Pellegrin

    Bordeaux, New Aquitaine, 33076

  • Centre d'Investigation Clinique de Lyon

    Bron, Auvergne-Rhône-Alpes, 69677

  • Hôpital Le Vinatier CRA Rhône-Alpes, Bat 211

    Bron, Auvergne-Rhône-Alpes, 69678

  • GSC CHU-LENVAL Centre ressource autisme

    Nice, Alpes-Maritimes, 6200

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

    Paris, Il de France, 75019

  • CHU Rouen

    Rouen, Normandy, 76000

  • Centre Hospitalier du Rouvray Centre de Ressources pour l'Autisme

    Sotteville-lès-Rouen, Normandy, 76301

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

    Strasbourg, Grand Est, 67091

Other trials in France

Italy7 sites

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

    Bosisio Parini, Lombardy, 23842

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

    Cagliari, Sardinia, 09131

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

    Calambrone, Tuscany, 56128

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

    Messina, Sicily, 98125

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

    Naples, Campania, 80131

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

    Pavia, Lombardy, 27100

  • U.O. di Neuropsichiatria Infantile Azienda Ospedaliera Universitaria Senese

    Siena, Tuscany, 53100

Other trials in Italy

Spain7 sites

  • Hospital General Universitario de Alicante

    Alicante, 03007

  • Hospital Clinic de Barcelona

    Barcelona, 08036

  • Policlinica Guipuzcoa

    Donostia / San Sebastian, Guipuzcoa, 20014

  • Hospital Niño Jesus

    Madrid, 28009

  • Hospital Universitario Gregorio Marañon

    Madrid, 28009

  • Hospital Puerta de Hierro

    Majadahonda, Madrid, 28222

  • Hospita Mutua de Terrassa

    Terrassa, Barcelona, 08221

Other trials in Spain

Brazil5 sites

  • Trial Tech em Pesquisas com Medicamentos Ltda

    Curitiba, 80240-280

  • Hospital Universitário Walter Cantídio - Universidade Federal do Ceará

    Fortaleza, 60430-370

  • Hospital São Vicente de Paulo

    Passo Fundo, 99010-080

  • Universidade Federal de São Paulo, Escola Paulista de Medicina

    São Paulo, 04017-030

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

    São Paulo, 054030-010

Other trials in Brazil

Poland5 sites

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

    Gdansk, Pomeranian Voivodeship, 80-542

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

    Gdansk, 80-546

  • NAVICULA Centrum Diagnozy i Terapii Autyzmu w Łodzi

    Lodz, Łódź Voivodeship, 91-129

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

    Warsaw, Masovian Voivodeship, 02-091

  • Fundacja SYNAPSIS ul.

    Warsaw, 02-085

Other trials in Poland

Hungary4 sites

  • Vadaskert Korhaz es Szakambulancia

    Budapest, 1021

  • Servus Salvus Kft.

    Budapest, 1026

  • Bekes Megyei Kozponti Korhaz Gyermek es ifjusagpszichiatriai osztaly

    Gyula, 5700

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

    Szeged, 6725

Other trials in Hungary

Germany3 sites

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

    Dresden, Saxony (Sachsen), 01307

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

    Freiburg im Breisgau, Baden-Wurttemberg, 79104

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

    Mannheim, Baden-Wurttemberg, 68159

Other trials in Germany

United Kingdom3 sites

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

    Birmingham, B4 6NH

  • ReCognition Health

    London, W1G 9JF

  • The Winnicott Centre

    Manchester, M13 0JE

Other trials in United Kingdom

Netherlands1 site

  • Accare Groningen

    Groningen, 9713 GZ

Other trials in Netherlands

Portugal1 site

  • Centro Hospitalar e Universitario de Coimbra Hospital Pediatrico

    Coimbra, 300-062

Other trials in Portugal

About this study

Official title: 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.

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.

Read the 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.

Being tested
Bumetanide Oral Solution, Placebo
Medical subject headings
Autism Spectrum Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bumetanide Oral SolutionDrug

    Oral Solution dosed at 0.5mg/mL Taken twice daily

  • PlaceboDrug

    Oral Solution Taken twice daily

Study groups in NCT03715166
Study groupRoleWhat they receive
Bumetanide/S95008ExperimentalNot described
Receives: Drug: Bumetanide Oral Solution
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Change from baseline to 6 month

Secondary outcomes (10)

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

    Efficacy criterion 65 items scale measuring symptoms associated with autism

    Measured: Change from baseline to 6 month

  2. Clinical Global Impression - Global Improvement (CGI-I) score

    Efficacy criterion Scale which assesses the severity of the illness and the global improvement of the patient under study treatment

    Measured: At 6 months

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

    Efficacy criterion Scale designated to measure adaptative behaviour

    Measured: Change from baseline to 6 month

  4. Adverse events and Paediatric Adverse Event Rating Scale (PAERS)

    Safety criterion Inventory report used to identify signs/symptoms experienced by the patient since the study treatment initiation.

    Measured: On average of 52 weeks

  5. Abnormalities in 12-leads electrocardiogram (ECG) parameters

    Safety criterion

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

  6. Renal ultrasound

    Safety criterion Assessment of the renal function

    Measured: selection visit/Week026/Week052

  7. the Columbia Suicide Severity Rating Scale Children's version (C-SSRS-C)

    Scale which assesses suicidal ideation and suicidal behaviour

    Measured: Week000/Week012/Week026/Week038/Week052

  8. Tanner stage

    Safety criterion Assessment of Pubertal development

    Measured: Week000/Week026/Week052

  9. Acceptability and palatability questionnaire

    Acceptability and palatability criterion Assessment of the ease of use to use the dosing device

    Measured: Week026

  10. Paediatric Quality of Life Inventory (PedsQL) questionnaire

    Quality of Life criterion Assessment of parent/legal representative perception of patient health related quality of life

    Measured: Week000/Week004/Week012/Week026/Week030/Week038/Week052

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Oct 2018
  2. Study start24 Sep 2018
  3. Primary completion13 Sep 2021
  4. Study completion13 Sep 2021

Why it stopped: The 6-month efficacy analysis did not show any significant difference between bumetanide versus placebo in the treatment of ASD in the overall studied population. No unexpected safety concerns were identified.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
6-month, randomized, double-blind, placebo-controlled, parallel groups followed by an open label active 6-month treatment period with bumetanide.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
211 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03715166
Sponsor's protocol ID
CL3-95008-001
Other IDs
2017-004419-38, 2017
Status last verified
Jul 2024
First submitted
12 Oct 2018
Last updated
25 Jul 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: * used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: * sponsored by Servier * with a first patient enrolled as of 1 January 2004 onwards * for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

Publications

  • 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.

    PubMed 37794745

  • 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.

    PubMed 39816573

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Bumetanide Oral Solution in people with Autism Spectrum Disorder (ASD), run by Institut de Recherches Internationales Servier at 45 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 45 sites in France, Italy, Spain, Brazil, Poland and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The 6-month efficacy analysis did not show any significant difference between bumetanide versus placebo in the treatment of ASD in the overall studied population. No unexpected safety concerns were identified.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Childhood Autism Rating Scale, Second Edition (CARS2) total raw score (time frame: Change from baseline to 6 month). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03715166, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2024.

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