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

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ClinicalTrials.gov Identifier: NCT03715153
Recruitment Status : Recruiting
First Posted : October 23, 2018
Last Update Posted : July 15, 2019
Sponsor:
Collaborator:
ADIR, a Servier Group company
Information provided by (Responsible Party):
Servier ( Institut de Recherches Internationales Servier )

Brief Summary:
The purpose of this study is to evaluate the efficacity and the safety of bumetanide/S95008 in the improvement of Autism Spectrum Disorder core symptoms.

Condition or disease Intervention/treatment Phase
Autism Spectrum Disorder (ASD) Drug: BUMETANIDE/S95008 Drug: PLACEBO Phase 3

Detailed Description:
The present study (CL3-95008-002) will be performed in children from 2 to less than 7 years old presenting with ASD. A 6-month double-blind treatment period will be performed in which efficacy and safety of bumetanide 0.5mg BID will be assessed versus placebo. This double-blind period will be followed by a 6-month open label treatment period of bumetanide 0.5mg BID in which long term safety will be evaluated.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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.
Actual Study Start Date : October 4, 2018
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Bumetanide

Arm Intervention/treatment
Experimental: BUMETANIDE/S95008 Drug: BUMETANIDE/S95008
Oral solution dosed at 0.5 mg/mL Taken twice daily.

Placebo Comparator: PLACEBO Drug: PLACEBO
Oral solution Taken twice daily.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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

  3. Vineland Adaptative Behaviour Scale II (VABS II) [ Time Frame: Change from baseline to 6 month ]
    Efficacy criterion Scale designated to measure adaptative behaviour

  4. Adverse Event and Pediatric 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.

  5. Abnormalities in 12-leads electrocardiogram (ECG) parameters [ Time Frame: Selection visit, Week004, Week008, Week012, Week026, Week030, Week034, Week038, Week052 ]
    Safety criterion

  6. Renal ultrasound [ Time Frame: Selection visit, Week026, Week052 ]
    Safety criterion Assessment of the renal function

  7. Columbia-Suicide severity scale Children's version (C-SSRS-C) [ Time Frame: Week000/Week012/Week026/Week038/Week052 ]
    Scale which assesses suicidal ideation and suicidal behaviour

  8. Acceptability and palatability questionnaires [ Time Frame: Week026 ]
    Acceptability and palatability criterion Assessment of the ease of use to use the dosing device

  9. Paediatric Quality of Life Inventory (PedsQL) questionnaire [ Time Frame: Week000/Week004/Week012/v026/Week030/Week038/Week052 ]
    Quality of Life questionnaire Assessment of parent/legal representative perception of patient health related quality of life



Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 6 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03715153


Contacts
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Contact: Institut de Recherches Internationales Servier Clinical Studies Department +33 1 55 72 43 66 clinicaltrials@servier.com

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Locations
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Australia
Liverpool Hospital Recruiting
Liverpool, Australia, 2170
The Royal Children's Hospital Melbourne Recruiting
Parkville, Australia, 3052
Contact       kylie.crompton@mcri.edu.au   
Brazil
Trial Tech em Pesquisas com Medicamentos Ltda Not yet recruiting
Curitiba, Brazil, 80240-280
Contact    +5541992061583    lfpetry@yahoo.com.br   
Hospital Universitário Walter Cantídio-Universidade Federal do Ceará Not yet recruiting
Fortaleza, Brazil, 60430-370
Contact    +55 85 98893 3337    jibiapinaneto@yahoo.com.br   
France
GSC CHU-LENVAL Centre ressource autisme Recruiting
Nice, Alpes-Maritimes, France, 6200
Contact: Sylvie Serret    +33 04 92 03 04 39    serret.s@pédiatrie-chulenval-nice.fr   
Hôpitaux Universitaires de Strasbourg Service de Psychiatrie de l'Enfant et de l'Adolescent Recruiting
Strasbourg, Alsace-Champagne-Ardenne-Lorraine, France, 67091
Contact: Isabelle Ohresser    +33 3 88 11 52 48    isabelle.ohresser@chrustrasbourg.fr   
Centre d'Investigation Clinique de Lyon Recruiting
Bron, Auvergne Rhone Alpes, France, 69677
Contact: sandrine mardirossian       sandrine.mardirossian@chu-lyon.fr   
Hôpital Le Vinatier CRA Rhône-Alpes, Bat 211 Recruiting
Bron Cedex, Auvergne-Rhône-Alpes, France, 69678
Contact: Sandrine Mardirossian       sandrine.mardirossian@chu-lyon.fr   
Hôpital Robert Debré Service de Psychiatrie de l'enfant et de l'adolescent Recruiting
Paris, Ile De France, France, 75019
Contact: Richard DELORME    +33 1 40 03 23 00    richard.delorme.rdb@gmail.com   
CHU Rouen Recruiting
Rouen, Normandie, France, 76000
Contact: Nathalie Mestre    02 32 88 57 84    Nathalie.Mestre@chu-rouen.fr   
Centre Hospitalier du Rouvray Centre de Ressources pour l'Autisme Recruiting
Sotteville-lès-Rouen, Normandie, France, 76301
Contact: Nathalie Mestre    +33 2 32 88 57 84    Nathalie.Mestre@chu-rouen.fr   
Hôpital des Enfants-Pellegrin Recruiting
Bordeaux, Nouvelle Aquitaine, France, 33076
Contact: Manuel Bouvard    +33 5.57.82.02.04    mbouvard@ch-perrens.fr   
Centre Hospitalier Charles Perrens CRA Aquitaine Recruiting
Bordeaux, Nouvelle-Aquitaine, France, 33076
Contact: Manuel BOUVARD    +33 5 56 56 17 19    mbouvard@ch-perrens.fr   
Germany
Universitätsklinikum Freiburg, Zentrum für Psychische Erkrankungen, Klinik für Psychiatrie, Psychotherapie und Psychosomatik im Kindes- und Jugendalter Recruiting
Freiburg, Baden-Württemberg, Germany, 79104
Contact: Christian Fleischhaker    004976127065550    christian.fleischhaker@uniklinik-freiburg.de   
Klinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters am Zentralinstitut für Seelische Gesundheit Recruiting
Mannheim, Baden-Württemberg, Germany, 68159
Universitätsklinikum Tübingen, Abt. Psychiatrie, Psychosomatik und Psychotherapie im Kindes- und Jugendalter Recruiting
Tuebingen, Baden-Württemberg, Germany, 72076
Universitätsklinikum Carl Gustav Carus an der TU Dresden, Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und-psychotherapie Recruiting
Dresden, Saxony (Sachsen), Germany, 01307
Contact: Yvonne Friedrich    +49 351 4587168    kjpforschung@ukdd.de   
Hungary
Vadaskert Korhaz es Szakambulancia Recruiting
Budapest, Hungary, 1021
Bekes Megyei Kozponti Korhaz Gyermek es ifjusagpszichiatriai osztaly Recruiting
Gyula, Hungary, 5700
Szegedi Tudományegyetem Szent-Gyorgy Albert Klinikai Kozpont Gyermekgyógyászati Klinika Gyermek es Ifjusagpszichiátriai o Recruiting
Szeged, Hungary, 6725
Italy
Neuro Riabilitazione/Psicopatologia dell'età evolutiva Istituto Scientifico Medea - Bosisio Parini Recruiting
Bosisio Parini, Lombardia, Italy, 23842
U.O. di Neuropsichiatria Infantile Fondazione Istituto Neurologico Nazionale Casimiro Mondino Istituto di Ricovero e Cura a Carattere Scientifico Recruiting
Pavia, Lombardia, Italy, 27100
Clinica di Neuropsichiatria dell'Infanzia e dell'Adolescenza Ospedale Pediatrico-Microcitemico Recruiting
Cagliari, Sardegna, Italy, 09131
Programma Interdipartimentale "Autismo 0-90" A.O.U. Policlinico "Gaetano Martino" Recruiting
Messina, Sicilia, Italy, 98125
U.O.C. Psichiatria dello Sviluppo IRCCS Fondazione Stella Maris Recruiting
Calambrone, Toscana, Italy, 56128
U.O. di Neuropsichiatria Infantile Azienda Ospedaliera Universitaria Senese Recruiting
Siena, Toscana, Italy, 53100
Poland
NAVICULA Centrum Diagnozy i Terapii Autyzmu w Łodzi Recruiting
Lodz, Wojewodztwo Lodzkie, Poland, 91-129
Samodzielny Publiczny Dziecięcy Szpital Kliniczny w Warszawie Oddział Kliniczny Psychiatrii Wieku Rozwojowego Recruiting
Warsaw, Wojewodztwo Mazowieckie, Poland, 02-091
"Niepubliczny Zakład Opieki Zdrowotnej Gdańskie Centrum Zdrowia Sp. z o.o. Recruiting
Gdansk, Wojewodztwo Pomorskie, Poland, 80-542
Portugal
Centro Hospitalar e Universitario de Coimbra Hospital Pediatrico Recruiting
Coimbra, Portugal, 300-062
Contact    + 351 96 554 7899    guiomar@chuc.min-saude.pt   
Spain
Hospita Mutua de Terrassa Recruiting
Terrassa, Barcelona, Spain, 08221
Contact: Amaia Hervas       ahervas@mutuaterrassa.es   
Policlinica Guipuzcoa Recruiting
San Sebastian, Guipuzcoa, Spain, 20014
Hospital Puerta de Hierro Recruiting
Majadahonda, Madrid, Spain, 28222
Contact: Inmaculada Palanca       farmacologia_clinica@idiphim.org   
Usm Infantil Benalua Recruiting
Alicante, Spain, 03007
Contact: Auxiliadora Javaloyes       javaloyes_marsan@gva.es   
Hospital Clinic de Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Rosa María Calvo Escalona    00 34 93 227 54 00 ext 4212    maredondo@clinic.cat   
Hospital Niño Jesus Recruiting
Madrid, Spain, 28009
Contact: Silvia Gutierrez Priego    00 34 91 5035900 ext 351    silvia.gutierrezp@salud.madrid.org   
Hospital Universitario Gregorio Marañon Recruiting
Madrid, Spain, 28009
United Kingdom
ReCognition Health Recruiting
London, United Kingdom, W1G 9JF
The Winnicott Centre 195-197 Hathersage Road Recruiting
Manchester, United Kingdom, M13 0JE
Sponsors and Collaborators
Institut de Recherches Internationales Servier
ADIR, a Servier Group company

Additional Information:
Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site

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Responsible Party: Institut de Recherches Internationales Servier
ClinicalTrials.gov Identifier: NCT03715153     History of Changes
Other Study ID Numbers: CL3-95008-002
2017-004420-30 ( EudraCT Number )
First Posted: October 23, 2018    Key Record Dates
Last Update Posted: July 15, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Researchers can ask for a study protocol, patient-level and/or study-level clinical trial data including clinical study reports (CSRs).

They can ask for all interventional clinical studies:

  • submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
  • Where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first Marketing Authorization of the new médicine (or the new indication) in one of the EEA Member States will be considered within this scope.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.
URL: http://clinicaltrials.servier.com/

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Disease
Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Pathologic Processes
Neurodevelopmental Disorders
Mental Disorders
Bumetanide
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action