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Autism Spectrum Disorder (ASD)Phase 3NCT03715153

Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.

A Phase 3 study testing BUMETANIDE (S95008) for week 0 - 26 and Open-Label BUMETANIDE (S95008) for weeks 26 - 52 in people with Autism Spectrum Disorder (ASD), run by Institut de Recherches Internationales Servier at 50 sites in 12 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 efficacity 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 2 to 6 years
Conditions the study is for
Autism Spectrum Disorder (ASD)
What is being tested?
BUMETANIDE (S95008) for week 0 - 26 and Open-Label BUMETANIDE (S95008) for weeks 26 - 52
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
50 sitesin 12 countries
Study dates
4 Oct 2018to 26 Oct 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 2 to 6 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.

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

50 sites in 12 countries.

50 sites in 12 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, Île-de-France Region, 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

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

Brazil6 sites
  • Trial Tech em Pesquisas com Medicamentos Ltda

    Curitiba, 80240-280

  • Hospital Universitário Walter Cantídio-Universidade Federal do Ceará

    Fortaleza, 60430-370

  • Clínica Neurológica e Neurocirúrgica de Joinville

    Joinville, 89202-190

  • 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 psiquiatra

    São Paulo, 054030-010

Other trials in Brazil

Italy6 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

  • 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

Hungary5 sites
  • Vadaskert Korhaz es Szakambulancia

    Budapest, 1021

  • Servus Salvus Kft.

    Budapest, 1026

  • Magyar Református Egyház Bethesda Gyermekkórháza

    Budapest, 1143

  • 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

Poland5 sites
  • "Niepubliczny Zakład Opieki Zdrowotnej Gdańskie Centrum Zdrowia Sp. z o.o.

    Gdansk, 80-542

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

    Gdansk, 80-546

  • NAVICULA Centrum Diagnozy i Terapii Autyzmu w Łodzi

    Lodz, 91-126

  • Fundacja SYNAPSIS ul.

    Warsaw, 02-085

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

    Warsaw, 02-091

Other trials in Poland

Czechia3 sites
  • University Hospital Brno, Department of Child Neurology

    Brno, 613 00

  • University hospital of Ostrava, Department of Psychiatry

    Poruba, Ostrava

  • Institute of Neuropsychiatric Care, Department of Child Psychiatry

    Prague, 186 00

Other trials in Czechia

United Kingdom3 sites
  • Colchester Hospital

    Colchester, CO4 5JL

  • ReCognition Health

    London, W1G 9JF

  • The Winnicott Centre 195-197 Hathersage Road

    Manchester, M13 0JE

Other trials in United Kingdom

Australia2 sites
  • Liverpool Hospital

    Liverpool, 2170

  • The Royal Children's Hospital Melbourne

    Parkville, 3052

Other trials in Australia

Slovakia2 sites
  • National Institute of Children Diseases, Department of Child Psychiatry

    Bratislava, 833 40

  • EPAMED, s.r.o.

    Košice, 040 01

Other trials in Slovakia

United States1 site
  • Richmond Behavioral Associates

    Staten Island, New York, 10312

Other trials in United States

Portugal1 site
  • Centro Hospitalar e Universitario de Coimbra Hospital Pediatrico

    Coimbra, 300-062

Other trials in Portugal

About this study

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.

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.

Read the 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.

Being tested
BUMETANIDE (S95008) for week 0 - 26, PLACEBO for week 0 - 26, Open-Label BUMETANIDE (S95008) for weeks 26 - 52
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 (S95008) for week 0 - 26Drug

    Oral solution dosed at 0.5 mg/mL Taken twice daily.

  • PLACEBO for week 0 - 26Drug

    Oral solution Taken twice daily.

  • Open-Label BUMETANIDE (S95008) for weeks 26 - 52Drug

    Oral solution dosed at 0.5 mg/mL Taken twice daily.

Study groups in NCT03715153
Study groupRoleWhat they receive
BUMETANIDE (S95008) followed by Open-Label S95008ExperimentalParticipants will receive S95008 for 6 months, 26 weeks, and then they will begin an open-label 6 month treatment period with S95008.
Receives: Drug: BUMETANIDE (S95008) for week 0 - 26; Drug: Open-Label BUMETANIDE (S95008) for weeks 26 - 52
PLACEBO followed by Open-Label S95008Placebo comparatorParticipants will receive placebo for 6 months, 26 weeks, and then they will begin an open-label 6 month treatment period with S95008.
Receives: Drug: PLACEBO for week 0 - 26; Drug: Open-Label BUMETANIDE (S95008) for weeks 26 - 52

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

    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.

    Measured: Change from baseline to Week 26

Secondary outcomes (8)
  1. Social Responsiveness Scale, Second Edition (SRS-2) Total Raw Score

    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.

    Measured: Change from baseline to Week 26

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

    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).

    Measured: At Week 26

  3. Vineland Adaptative Behaviour Scale II (VABS II)

    Scale designated to measure adaptative behaviour The scale for behaviour ranges from 1 to 67. The more the score decreases, the better it is.

    Measured: Change from baseline to Week 26

  4. Number of Patients With Abnormalities in 12-leads Electrocardiogram (ECG) Parameters

    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.

    Measured: Week 26

  5. Columbia-Suicide Severity Scale Children's Version (C-SSRS-C)

    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.

    Measured: Week 26

  6. Acceptability and Palatability Questionnaires - Only Descriptive Analyses

    Acceptability and palatability criterion Based on your child's reactions (indirect rating), do you think that he/she found the administration method to be

    Measured: Week 26

  7. Paediatric Quality of Life Inventory (PedsQL) Questionnaire

    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)

    Measured: Change from baseline to week 26

  8. Number of Participants Experiencing at Least 1 Treatment Emergent Adverse Event (TEAE)

    Measured: through week 52

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 start4 Oct 2018
  3. Primary completion26 Oct 2021
  4. Study completion26 Oct 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
NCT03715153
Sponsor's protocol ID
CL3-95008-002
Other IDs
2017-004420-30, 2017
Status last verified
May 2023
First submitted
12 Oct 2018
Last updated
5 Jun 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
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

  • 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
  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing BUMETANIDE (S95008) for week 0 - 26 and Open-Label BUMETANIDE (S95008) for weeks 26 - 52 in people with Autism Spectrum Disorder (ASD), run by Institut de Recherches Internationales Servier at 50 sites in 12 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 8 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 5 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 50 sites in France, Spain, Brazil, Italy, Hungary and 7 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?

Yes. Results are posted in the registry (first posted 5 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 Week 26). 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 NCT03715153, 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 5 Jun 2023.

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