NCT03715153

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.

Trial Health

68
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
211

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Oct 2018

Typical duration for phase_3

Geographic Reach
12 countries

50 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 4, 2018

Completed
8 days until next milestone

First Submitted

Initial submission to the registry

October 12, 2018

Completed
11 days until next milestone

First Posted

Study publicly available on registry

October 23, 2018

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 26, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 26, 2021

Completed
1.6 years until next milestone

Results Posted

Study results publicly available

June 5, 2023

Completed
Last Updated

June 5, 2023

Status Verified

May 1, 2023

Enrollment Period

3.1 years

First QC Date

October 12, 2018

Results QC Date

October 26, 2022

Last Update Submit

May 9, 2023

Conditions

Outcome Measures

Primary Outcomes (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.

    Change from baseline to Week 26

Secondary Outcomes (8)

  • Social Responsiveness Scale, Second Edition (SRS-2) Total Raw Score

    Change from baseline to Week 26

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

    At Week 26

  • Vineland Adaptative Behaviour Scale II (VABS II)

    Change from baseline to Week 26

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

    Week 26

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

    Week 26

  • +3 more secondary outcomes

Study Arms (2)

BUMETANIDE (S95008) followed by Open-Label S95008

EXPERIMENTAL

Participants will receive S95008 for 6 months, 26 weeks, and then they will begin an open-label 6 month treatment period with S95008.

Drug: BUMETANIDE (S95008) for week 0 - 26Drug: Open-Label BUMETANIDE (S95008) for weeks 26 - 52

PLACEBO followed by Open-Label S95008

PLACEBO COMPARATOR

Participants will receive placebo for 6 months, 26 weeks, and then they will begin an open-label 6 month treatment period with S95008.

Drug: PLACEBO for week 0 - 26Drug: Open-Label BUMETANIDE (S95008) for weeks 26 - 52

Interventions

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

BUMETANIDE (S95008) followed by Open-Label S95008

Oral solution Taken twice daily.

PLACEBO followed by Open-Label S95008

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

BUMETANIDE (S95008) followed by Open-Label S95008PLACEBO followed by Open-Label S95008

Eligibility Criteria

Age2 Years - 6 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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.

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (50)

Richmond Behavioral Associates

Staten Island, New York, 10312, United States

Location

Liverpool Hospital

Liverpool, 2170, Australia

Location

The Royal Children's Hospital Melbourne

Parkville, 3052, Australia

Location

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

Clínica Neurológica e Neurocirúrgica de Joinville

Joinville, 89202-190, 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 psiquiatra

São Paulo, 054030-010, Brazil

Location

University hospital of Ostrava, Department of Psychiatry

Poruba, Ostrava, Czechia

Location

University Hospital Brno, Department of Child Neurology

Brno, 613 00, Czechia

Location

Institute of Neuropsychiatric Care, Department of Child Psychiatry

Prague, 186 00, Czechia

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

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

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

Paris, Île-de-France Region, 75019, France

Location

Vadaskert Korhaz es Szakambulancia

Budapest, 1021, Hungary

Location

Servus Salvus Kft.

Budapest, 1026, Hungary

Location

Magyar Református Egyház Bethesda Gyermekkórháza

Budapest, 1143, 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

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

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

Gdansk, 80-542, Poland

Location

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

Gdansk, 80-546, Poland

Location

NAVICULA Centrum Diagnozy i Terapii Autyzmu w Łodzi

Lodz, 91-126, Poland

Location

Fundacja SYNAPSIS ul.

Warsaw, 02-085, Poland

Location

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

Warsaw, 02-091, Poland

Location

Centro Hospitalar e Universitario de Coimbra Hospital Pediatrico

Coimbra, 300-062, Portugal

Location

National Institute of Children Diseases, Department of Child Psychiatry

Bratislava, 833 40, Slovakia

Location

EPAMED, s.r.o.

Košice, 040 01, Slovakia

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

Colchester Hospital

Colchester, CO4 5JL, United Kingdom

Location

ReCognition Health

London, W1G 9JF, United Kingdom

Location

The Winnicott Centre 195-197 Hathersage Road

Manchester, M13 0JE, United Kingdom

Location

Related Publications (2)

  • 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.

  • 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.

MeSH Terms

Conditions

Autism Spectrum Disorder

Interventions

Bumetanide

Condition Hierarchy (Ancestors)

Child Development Disorders, PervasiveNeurodevelopmental DisordersMental Disorders

Intervention Hierarchy (Ancestors)

SulfonamidesAmidesOrganic Chemicalsmeta-AminobenzoatesAminobenzoatesBenzoatesAcids, CarbocyclicCarboxylic AcidsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSulfonesSulfur Compounds

Limitations and Caveats

The sponsor decided to stop the S95008 development and prematurely discontinue the extension period. This decision was not related to unexpected safety concerns.

Results Point of Contact

Title
Dr. Pierre-François PENELAUD
Organization
Institut de Recherches Internationales Servier (I.R.I.S.)

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

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

Study Record Dates

First Submitted

October 12, 2018

First Posted

October 23, 2018

Study Start

October 4, 2018

Primary Completion

October 26, 2021

Study Completion

October 26, 2021

Last Updated

June 5, 2023

Results First Posted

June 5, 2023

Record last verified: 2023-05

Data Sharing

IPD Sharing
Will share

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.

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.
More information

Available IPD Datasets

Individual Participant Data Set Access
Study Protocol Access
Statistical Analysis Plan Access
Informed Consent Form Access
Clinical Study Report Access
study-level clinical trial data] Access

Locations