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

Autism Spectrum Disorder (ASD) Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03715153
• Other study ID #: CL3-95008-002
• Secondary ID: 2017-004420-30
• Status: Terminated
• Phase: Phase 3
• Start date: October 4, 2018
• Est. completion date: October 26, 2021

Study information

• Verified date: May 2023
• Source: Servier
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 211
• Est. completion date: October 26, 2021
• Est. primary completion date: October 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 6 Years

Eligibility

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

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autism Spectrum Disorder (ASD)
• Autistic Disorder
• Child Development Disorders, Pervasive

Intervention

Drug:
• BUMETANIDE (S95008) for week 0 - 26
Oral solution dosed at 0.5 mg/mL Taken twice daily.
• PLACEBO for week 0 - 26
Oral solution Taken twice daily.
• Open-Label BUMETANIDE (S95008) for weeks 26 - 52
Oral solution dosed at 0.5 mg/mL Taken twice daily.

Locations

Country	Name	City	State
Australia	Liverpool Hospital	Liverpool
Australia	The Royal Children's Hospital Melbourne	Parkville
Brazil	Trial Tech em Pesquisas com Medicamentos Ltda	Curitiba
Brazil	Hospital Universitário Walter Cantídio-Universidade Federal do Ceará	Fortaleza
Brazil	Clínica Neurológica e Neurocirúrgica de Joinville	Joinville
Brazil	Hospital São Vicente de Paulo	Passo Fundo
Brazil	Faculdade de Medicina da Universidade de São Paulo - Departamento de psiquiatra	São Paulo
Brazil	Universidade Federal de São Paulo, Escola Paulista de Medicina	São Paulo
Czechia	University Hospital Brno, Department of Child Neurology	Brno
Czechia	University hospital of Ostrava, Department of Psychiatry	Poruba	Ostrava
Czechia	Institute of Neuropsychiatric Care, Department of Child Psychiatry	Praha
France	Centre Hospitalier Charles Perrens CRA Aquitaine	Bordeaux	Nouvelle-Aquitaine
France	Hôpital des Enfants-Pellegrin	Bordeaux	Nouvelle Aquitaine
France	Centre d'Investigation Clinique de Lyon	Bron	Auvergne Rhone Alpes
France	Hôpital Le Vinatier CRA Rhône-Alpes, Bat 211	Bron Cedex	Auvergne-Rhône-Alpes
France	GSC CHU-LENVAL Centre ressource autisme	Nice	Alpes-Maritimes
France	Hôpital Robert Debré Service de Psychiatrie de l'enfant et de l'adolescent	Paris	Ile De France
France	CHU Rouen	Rouen	Normandie
France	Centre Hospitalier du Rouvray Centre de Ressources pour l'Autisme	Sotteville-lès-Rouen	Normandie
France	Hôpitaux Universitaires de Strasbourg Service de Psychiatrie de l'Enfant et de l'Adolescent	Strasbourg	Alsace-Champagne-Ardenne-Lorraine
Hungary	Magyar Református Egyház Bethesda Gyermekkórháza	Budapest
Hungary	Servus Salvus Kft.	Budapest
Hungary	Vadaskert Korhaz es Szakambulancia	Budapest
Hungary	Bekes Megyei Kozponti Korhaz Gyermek es ifjusagpszichiatriai osztaly	Gyula
Hungary	Szegedi Tudományegyetem Szent-Gyorgy Albert Klinikai Kozpont Gyermekgyógyászati Klinika Gyermek es Ifjusagpszichiátriai o	Szeged
Italy	Neuro Riabilitazione/Psicopatologia dell'età evolutiva Istituto Scientifico Medea - Bosisio Parini	Bosisio Parini	Lombardia
Italy	Clinica di Neuropsichiatria dell'Infanzia e dell'Adolescenza Ospedale Pediatrico-Microcitemico	Cagliari	Sardegna
Italy	U.O.C. Psichiatria dello Sviluppo IRCCS Fondazione Stella Maris	Calambrone	Toscana
Italy	Programma Interdipartimentale "Autismo 0-90" A.O.U. Policlinico "Gaetano Martino"	Messina	Sicilia
Italy	U.O. di Neuropsichiatria Infantile Fondazione Istituto Neurologico Nazionale Casimiro Mondino Istituto di Ricovero e Cura a Carattere Scientifico	Pavia	Lombardia
Italy	U.O. di Neuropsichiatria Infantile Azienda Ospedaliera Universitaria Senese	Siena	Toscana
Poland	"Niepubliczny Zaklad Opieki Zdrowotnej Gdanskie Centrum Zdrowia Sp. z o.o.	Gdansk
Poland	Centrum Badan Klinicznych PI-House sp. z o.o	Gdansk
Poland	NAVICULA Centrum Diagnozy i Terapii Autyzmu w Lodzi	Lodz
Poland	Fundacja SYNAPSIS ul.	Warszawa
Poland	Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie Oddzial Kliniczny Psychiatrii Wieku Rozwojowego	Warszawa
Portugal	Centro Hospitalar e Universitario de Coimbra Hospital Pediatrico	Coimbra
Slovakia	National Institute of Children Diseases, Department of Child Psychiatry	Bratislava
Slovakia	EPAMED, s.r.o.	Košice
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Niño Jesus	Madrid
Spain	Hospital Universitario Gregorio Marañon	Madrid
Spain	Hospital Puerta de Hierro	Majadahonda	Madrid
Spain	Policlinica Guipuzcoa	San Sebastian	Guipuzcoa
Spain	Hospita Mutua de Terrassa	Terrassa	Barcelona
United Kingdom	Colchester Hospital	Colchester
United Kingdom	ReCognition Health	London
United Kingdom	The Winnicott Centre 195-197 Hathersage Road	Manchester
United States	Richmond Behavioral Associates	Staten Island	New York

Sponsors (2)

Lead Sponsor	Collaborator
Institut de Recherches Internationales Servier	ADIR, a Servier Group company

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Czechia,  France,  Hungary,  Italy,  Poland,  Portugal,  Slovakia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Change from baseline to Week 26
Secondary	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).	At Week 26
Secondary	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.	Change from baseline to Week 26
Secondary	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.	Week 26
Secondary	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.	Week 26
Secondary	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	Week 26
Secondary	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)	Change from baseline to week 26
Secondary	Number of Participants Experiencing at Least 1 Treatment Emergent Adverse Event (TEAE)		through week 52

External Links

•   Lay summary
•   Results summary