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

Autism Spectrum Disorder (ASD) Clinical Trial

Official title:

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: NCT03715166
• Other study ID #: CL3-95008-001
• Secondary ID: 2017-004419-38
• Status: Terminated
• Phase: Phase 3
• Start date: September 24, 2018
• Est. completion date: September 13, 2021

Study information

• Verified date: March 2022
• Source: Servier
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 211
• Est. completion date: September 13, 2021
• Est. primary completion date: September 13, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autism Spectrum Disorder (ASD)

Intervention

Drug:
• Bumetanide Oral Solution
Oral Solution dosed at 0.5mg/mL Taken twice daily
• Placebo
Oral Solution Taken twice daily

Locations

Country	Name	City	State
Brazil	Trial Tech em Pesquisas com Medicamentos Ltda	Curitiba
Brazil	Hospital Universitário Walter Cantídio - Universidade Federal do Ceará	Fortaleza
Brazil	Hospital São Vicente de Paulo	Passo Fundo
Brazil	Faculdade de Medicina da Universidade de São Paulo - Departamento de Psiquiatria	São Paulo
Brazil	Universidade Federal de São Paulo, Escola Paulista de Medicina	São Paulo
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	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	Il 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
Germany	Universitätsklinikum Carl Gustav Carus an der TU Dresden, Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und	Dresden	Saxony (Sachsen)
Germany	Universitätsklinikum Freiburg, Zentrum für Psychische Erkrankungen, Klinik für Psychiatrie, Psychotherapie und Psychosomatik im Kindes- und Jugendalter	Freiburg	Baden-Württemberg
Germany	Klinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters am Zentralinstitut für Seelische Gesundheit	Mannheim	Baden-Württemberg
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	Unità Semplice di Psichiatria Infantile Policlinico Universitario di Napoli - Università Federico II	Napoli	Campania
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
Netherlands	Accare Groningen	Groningen
Poland	Centrum Badan Klinicznych PI-House sp. z o.o	Gdansk
Poland	Niepubliczny Zaklad Opieki Zdrowotnej Gdanskie Centrum Zdrowia Sp. z o.o.	Gdansk	Wojewodztwo Pomorskie
Poland	NAVICULA Centrum Diagnozy i Terapii Autyzmu w Lodzi	Lodz	Wojewodztwo Lodzkie
Poland	Fundacja SYNAPSIS ul.	Warszawa
Poland	Samodzielny Publiczny Dzieciecy Szpital Kliniczny w Warszawie Oddzial Kliniczny Psychiatrii Wieku Rozwojowego	Warszawa	Wojewodztwo Mazowieckie
Portugal	Centro Hospitalar e Universitario de Coimbra Hospital Pediatrico	Coimbra
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	Forward Thinking Birmingham_Birmingham Women's and Children's NHS Foundation Trust	Birmingham
United Kingdom	ReCognition Health	London
United Kingdom	The Winnicott Centre	Manchester

Sponsors (2)

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

Countries where clinical trial is conducted

Brazil,  France,  Germany,  Hungary,  Italy,  Netherlands,  Poland,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Childhood Autism Rating Scale, Second Edition (CARS2) total raw score	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	Social Responsiveness Scale, Second Edition (SRS-2) total raw score	Efficacy criterion 65 items scale measuring symptoms associated with autism	Change from baseline to 6 month
Secondary	Clinical Global Impression - Global Improvement (CGI-I) score	Efficacy criterion Scale which assesses the severity of the illness and the global improvement of the patient under study treatment	At 6 months
Secondary	Vineland Adaptative Behaviour Sales, Second Edition (VABS II) subscores	Efficacy criterion Scale designated to measure adaptative behaviour	Change from baseline to 6 month
Secondary	Adverse events and Paediatric Adverse Event Rating Scale (PAERS)	Safety criterion Inventory report used to identify signs/symptoms experienced by the patient since the study treatment initiation.	On average of 52 weeks
Secondary	Abnormalities in 12-leads electrocardiogram (ECG) parameters	Safety criterion	selection visit/Week004/Week008/Week012/Week 026/Week030/Week034/Week038/Week052
Secondary	Renal ultrasound	Safety criterion Assessment of the renal function	selection visit/Week026/Week052
Secondary	the Columbia Suicide Severity Rating Scale Children's version (C-SSRS-C)	Scale which assesses suicidal ideation and suicidal behaviour	Week000/Week012/Week026/Week038/Week052
Secondary	Tanner stage	Safety criterion Assessment of Pubertal development	Week000/Week026/Week052
Secondary	Acceptability and palatability questionnaire	Acceptability and palatability criterion Assessment of the ease of use to use the dosing device	Week026
Secondary	Paediatric Quality of Life Inventory (PedsQL) questionnaire	Quality of Life criterion Assessment of parent/legal representative perception of patient health related quality of life	Week000/Week004/Week012/Week026/Week030/Week038/Week052

External Links

•   Lay summary
•   Results summary