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

March 11, 2022 updated by: Institut de Recherches Internationales Servier

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

211

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • Curitiba, Brazil, 80240-280
        • Trial Tech em Pesquisas com Medicamentos Ltda
      • Fortaleza, Brazil, 60430-370
        • Hospital Universitario Walter Cantidio - Universidade Federal do Ceara
      • Passo Fundo, Brazil, 99010-080
        • Hospital Sao Vicente de Paulo
      • São Paulo, Brazil, 04017-030
        • Universidade Federal de São Paulo, Escola Paulista de Medicina
      • São Paulo, Brazil, 054030-010
        • Faculdade de Medicina da Universidade de São Paulo - Departamento de Psiquiatria
  • France
    • Alpes-Maritimes
      • Nice, Alpes-Maritimes, France, 6200
        • GSC CHU-LENVAL Centre ressource autisme
    • Alsace-Champagne-Ardenne-Lorraine
      • Strasbourg, Alsace-Champagne-Ardenne-Lorraine, France, 67091
        • Hôpitaux Universitaires de Strasbourg Service de Psychiatrie de l'Enfant et de l'Adolescent
    • Auvergne Rhone Alpes
      • Bron, Auvergne Rhone Alpes, France, 69677
        • Centre d'Investigation Clinique de Lyon
    • Auvergne-Rhône-Alpes
      • Bron, Auvergne-Rhône-Alpes, France, 69678
        • Hôpital Le Vinatier CRA Rhône-Alpes, Bat 211
    • Il De France
      • Paris, Il De France, France, 75019
        • Hôpital Robert Debré Service de Psychiatrie de l'enfant et de l'adolescent
    • Normandie
      • Rouen, Normandie, France, 76000
        • CHU Rouen
      • Sotteville-lès-Rouen, Normandie, France, 76301
        • Centre Hospitalier du Rouvray Centre de Ressources pour l'Autisme
    • Nouvelle Aquitaine
      • Bordeaux, Nouvelle Aquitaine, France, 33076
        • Hôpital des Enfants-Pellegrin
    • Nouvelle-Aquitaine
      • Bordeaux, Nouvelle-Aquitaine, France, 33076
        • Centre Hospitalier Charles Perrens CRA Aquitaine
  • Germany
    • Baden-Württemberg
      • Freiburg, Baden-Württemberg, Germany, 79104
        • Universitätsklinikum Freiburg, Zentrum für Psychische Erkrankungen, Klinik für Psychiatrie, Psychotherapie und Psychosomatik im Kindes- und Jugendalter
      • Mannheim, Baden-Württemberg, Germany, 68159
        • Klinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters am Zentralinstitut für Seelische Gesundheit
    • Saxony (Sachsen)
      • Dresden, Saxony (Sachsen), Germany, 01307
        • Universitätsklinikum Carl Gustav Carus an der TU Dresden, Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und
  • Hungary
      • Budapest, Hungary, 1021
        • Vadaskert Korhaz es Szakambulancia
      • Budapest, Hungary, 1026
        • Servus Salvus Kft.
      • Gyula, Hungary, 5700
        • Bekes Megyei Kozponti Korhaz Gyermek es ifjusagpszichiatriai osztaly
      • Szeged, Hungary, 6725
        • Szegedi Tudományegyetem Szent-Gyorgy Albert Klinikai Kozpont Gyermekgyógyászati Klinika Gyermek es Ifjusagpszichiátriai o
  • Italy
    • Campania
      • Napoli, Campania, Italy, 80131
        • Unità Semplice di Psichiatria Infantile Policlinico Universitario di Napoli - Università Federico II
    • Lombardia
      • Bosisio Parini, Lombardia, Italy, 23842
        • Neuro Riabilitazione/Psicopatologia dell'età evolutiva Istituto Scientifico Medea - Bosisio Parini
      • Pavia, Lombardia, Italy, 27100
        • U.O. di Neuropsichiatria Infantile Fondazione Istituto Neurologico Nazionale Casimiro Mondino Istituto di Ricovero e Cura a Carattere Scientifico
    • Sardegna
      • Cagliari, Sardegna, Italy, 09131
        • Clinica di Neuropsichiatria dell'Infanzia e dell'Adolescenza Ospedale Pediatrico-Microcitemico
    • Sicilia
      • Messina, Sicilia, Italy, 98125
        • Programma Interdipartimentale "Autismo 0-90" A.O.U. Policlinico "Gaetano Martino"
    • Toscana
      • Calambrone, Toscana, Italy, 56128
        • U.O.C. Psichiatria dello Sviluppo IRCCS Fondazione Stella Maris
      • Siena, Toscana, Italy, 53100
        • U.O. di Neuropsichiatria Infantile Azienda Ospedaliera Universitaria Senese
  • Netherlands
      • Groningen, Netherlands, 9713 GZ
        • Accare Groningen
  • Poland
      • Gdansk, Poland, 80-546
        • Centrum Badań Klinicznych PI-House sp. z o.o
      • Warszawa, Poland, 02-085
        • Fundacja SYNAPSIS ul.
    • Wojewodztwo Lodzkie
      • Lodz, Wojewodztwo Lodzkie, Poland, 91-129
        • NAVICULA Centrum Diagnozy i Terapii Autyzmu w Łodzi
    • Wojewodztwo Mazowieckie
      • Warszawa, Wojewodztwo Mazowieckie, Poland, 02-091
        • Samodzielny Publiczny Dziecięcy Szpital Kliniczny w Warszawie Oddział Kliniczny Psychiatrii Wieku Rozwojowego
    • Wojewodztwo Pomorskie
      • Gdansk, Wojewodztwo Pomorskie, Poland, 80-542
        • Niepubliczny Zakład Opieki Zdrowotnej Gdańskie Centrum Zdrowia Sp. z o.o.
  • Portugal
      • Coimbra, Portugal, 300-062
        • Centro Hospitalar e Universitario de Coimbra Hospital Pediatrico
  • Spain
      • Alicante, Spain, 03007
        • Hospital General Universitario de Alicante
      • Barcelona, Spain, 08036
        • Hospital Clinic de Barcelona
      • Madrid, Spain, 28009
        • Hospital Universitario Gregorio Marañón
      • Madrid, Spain, 28009
        • Hospital Niño Jesús
    • Barcelona
      • Terrassa, Barcelona, Spain, 08221
        • Hospita Mutua de Terrassa
    • Guipuzcoa
      • San Sebastian, Guipuzcoa, Spain, 20014
        • Policlinica Guipuzcoa
    • Madrid
      • Majadahonda, Madrid, Spain, 28222
        • Hospital Puerta de Hierro
  • United Kingdom
      • Birmingham, United Kingdom, B4 6NH
        • Forward Thinking Birmingham_Birmingham Women's and Children's NHS Foundation Trust
      • London, United Kingdom, W1G 9JF
        • Recognition Health
      • Manchester, United Kingdom, M13 0JE
        • The Winnicott Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years to 15 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
Oral Solution Taken twice daily
Experimental: Bumetanide/S95008
Drug: Bumetanide Oral Solution
Oral Solution dosed at 0.5mg/mL Taken twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Childhood Autism Rating Scale, Second Edition (CARS2) total raw score
Time Frame: Change from baseline to 6 month
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Social Responsiveness Scale, Second Edition (SRS-2) total raw score
Time Frame: Change from baseline to 6 month
Efficacy criterion 65 items scale measuring symptoms associated with autism
Change from baseline to 6 month
Clinical Global Impression - Global Improvement (CGI-I) score
Time Frame: At 6 months
Efficacy criterion Scale which assesses the severity of the illness and the global improvement of the patient under study treatment
At 6 months
Vineland Adaptative Behaviour Sales, Second Edition (VABS II) subscores
Time Frame: Change from baseline to 6 month
Efficacy criterion Scale designated to measure adaptative behaviour
Change from baseline to 6 month
Adverse events and Paediatric Adverse Event Rating Scale (PAERS)
Time Frame: On average of 52 weeks
Safety criterion Inventory report used to identify signs/symptoms experienced by the patient since the study treatment initiation.
On average of 52 weeks
Abnormalities in 12-leads electrocardiogram (ECG) parameters
Time Frame: selection visit/Week004/Week008/Week012/Week 026/Week030/Week034/Week038/Week052
Safety criterion
selection visit/Week004/Week008/Week012/Week 026/Week030/Week034/Week038/Week052
Renal ultrasound
Time Frame: selection visit/Week026/Week052
Safety criterion Assessment of the renal function
selection visit/Week026/Week052
the Columbia Suicide Severity Rating Scale Children's version (C-SSRS-C)
Time Frame: Week000/Week012/Week026/Week038/Week052
Scale which assesses suicidal ideation and suicidal behaviour
Week000/Week012/Week026/Week038/Week052
Tanner stage
Time Frame: Week000/Week026/Week052
Safety criterion Assessment of Pubertal development
Week000/Week026/Week052
Acceptability and palatability questionnaire
Time Frame: Week026
Acceptability and palatability criterion Assessment of the ease of use to use the dosing device
Week026
Paediatric Quality of Life Inventory (PedsQL) questionnaire
Time Frame: Week000/Week004/Week012/Week026/Week030/Week038/Week052
Quality of Life criterion Assessment of parent/legal representative perception of patient health related quality of life
Week000/Week004/Week012/Week026/Week030/Week038/Week052

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut de Recherches Internationales Servier

Collaborators

ADIR, a Servier Group company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 24, 2018

Primary Completion (Actual)

September 13, 2021

Study Completion (Actual)

September 13, 2021

Study Registration Dates

First Submitted

October 12, 2018

First Submitted That Met QC Criteria

October 18, 2018

First Posted (Actual)

October 23, 2018

Study Record Updates

Last Update Posted (Actual)

March 29, 2022

Last Update Submitted That Met QC Criteria

March 11, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CL3-95008-001
  • 2017-004419-38 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

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.

IPD Sharing Time Frame

After Marketing Authorisation in EEA or US if the study is used for the approval.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)

Study Data/Documents

  1. Individual Participant Data Set
  2. Study Protocol
  3. Statistical Analysis Plan
  4. Informed Consent Form
  5. Clinical Study Report
  6. study-level clinical trial data

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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