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

NCT ID: NCT03715153

Last Updated: 2023-06-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 211 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-04
• Study Completion Date: 2021-10-26

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.

Detailed 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.

Conditions

Autism Spectrum Disorder (ASD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

BUMETANIDE (S95008) followed by Open-Label S95008

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

Group Type: EXPERIMENTAL

BUMETANIDE (S95008) for week 0 - 26

Intervention Type: DRUG

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

Open-Label BUMETANIDE (S95008) for weeks 26 - 52

Intervention Type: DRUG

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

PLACEBO followed by Open-Label S95008

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

Group Type: PLACEBO_COMPARATOR

PLACEBO for week 0 - 26

Intervention Type: DRUG

Oral solution Taken twice daily.

Open-Label BUMETANIDE (S95008) for weeks 26 - 52

Intervention Type: DRUG

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

Interventions

BUMETANIDE (S95008) for week 0 - 26

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

Intervention Type: DRUG

PLACEBO for week 0 - 26

Oral solution Taken twice daily.

Intervention Type: DRUG

Open-Label BUMETANIDE (S95008) for weeks 26 - 52

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

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ADIR, a Servier Group company

INDUSTRY

Sponsor Role: collaborator

Institut de Recherches Internationales Servier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Richmond Behavioral Associates

Staten Island, New York, United States

Liverpool Hospital

Liverpool, , Australia

The Royal Children's Hospital Melbourne

Parkville, , Australia

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

Universidade Federal de São Paulo, Escola Paulista de Medicina

São Paulo, , Brazil

Faculdade de Medicina da Universidade de São Paulo - Departamento de psiquiatra

São Paulo, , Brazil

University hospital of Ostrava, Department of Psychiatry

Poruba, Ostrava, Czechia

University Hospital Brno, Department of Child Neurology

Brno, , Czechia

Institute of Neuropsychiatric Care, Department of Child Psychiatry

Prague, , Czechia

GSC CHU-LENVAL Centre ressource autisme

Nice, Alpes-Maritimes, France

Centre d'Investigation Clinique de Lyon

Bron, Auvergne-Rhône-Alpes, France

Hôpital Le Vinatier CRA Rhône-Alpes, Bat 211

Bron, Auvergne-Rhône-Alpes, France

Hôpitaux Universitaires de Strasbourg Service de Psychiatrie de l'Enfant et de l'Adolescent

Strasbourg, Grand Est, France

CHU Rouen

Rouen, Normandy, France

Centre Hospitalier du Rouvray Centre de Ressources pour l'Autisme

Sotteville-lès-Rouen, Normandy, France

Centre Hospitalier Charles Perrens CRA Aquitaine

Bordeaux, Nouvelle-Aquitaine, France

Hôpital des Enfants-Pellegrin

Bordeaux, Nouvelle-Aquitaine, France

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

Paris, Île-de-France Region, France

Vadaskert Korhaz es Szakambulancia

Budapest, , Hungary

Servus Salvus Kft.

Budapest, , Hungary

Magyar Református Egyház Bethesda Gyermekkórháza

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, , Hungary

Neuro Riabilitazione/Psicopatologia dell'età evolutiva Istituto Scientifico Medea - Bosisio Parini

Bosisio Parini, Lombardy, Italy

U.O. di Neuropsichiatria Infantile Fondazione Istituto Neurologico Nazionale Casimiro Mondino Istituto di Ricovero e Cura a Carattere Scientifico

Pavia, Lombardy, Italy

Clinica di Neuropsichiatria dell'Infanzia e dell'Adolescenza Ospedale Pediatrico-Microcitemico

Cagliari, Sardinia, Italy

Programma Interdipartimentale "Autismo 0-90" A.O.U. Policlinico "Gaetano Martino"

Messina, Sicily, Italy

U.O.C. Psichiatria dello Sviluppo IRCCS Fondazione Stella Maris

Calambrone, Tuscany, Italy

U.O. di Neuropsichiatria Infantile Azienda Ospedaliera Universitaria Senese

Siena, Tuscany, Italy

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

Gdansk, , Poland

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

Gdansk, , Poland

NAVICULA Centrum Diagnozy i Terapii Autyzmu w Łodzi

Lodz, , Poland

Fundacja SYNAPSIS ul.

Warsaw, , Poland

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

Warsaw, , Poland

Centro Hospitalar e Universitario de Coimbra Hospital Pediatrico

Coimbra, , Portugal

National Institute of Children Diseases, Department of Child Psychiatry

Bratislava, , Slovakia

EPAMED, s.r.o.

Košice, , Slovakia

Hospita Mutua de Terrassa

Terrassa, Barcelona, Spain

Policlinica Guipuzcoa

Donostia / San Sebastian, Guipuzcoa, Spain

Hospital Puerta de Hierro

Majadahonda, Madrid, 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

Colchester Hospital

Colchester, , United Kingdom

ReCognition Health

London, , United Kingdom

The Winnicott Centre 195-197 Hathersage Road

Manchester, , United Kingdom

Countries

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

References

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.

Reference Type: DERIVED

PMID: 39816573 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37794745 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Study Documents

Document Type: Individual Participant Data Set

View Document

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Document Type: Clinical Study Report

View Document

Document Type: study-level clinical trial data]

View Document

Other Identifiers

2017-004420-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CL3-95008-002

Identifier Type: -

Identifier Source: org_study_id