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

Phase 3

Terminated

• Conditions: Autism Spectrum Disorder (ASD)
• Interventions: Drug: Bumetanide Oral Solution; Drug: Placebo

• Registration Number: NCT03715166
• Lead Sponsor: Institut de Recherches Internationales Servier

Brief 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.

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 Timeline

• Study Start: 2018-09-24
• Study First Submitted: 2018-10-12
• Study First Submitted QC: 2018-10-18
• Study First Posted: 2018-10-23
• Primary Completion: 2021-09-13
• Study Completion: 2021-09-13
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-24
• Last Update Posted: 2024-07-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 211

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bumetanide/S95008	Bumetanide Oral Solution	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Childhood Autism Rating Scale, Second Edition (CARS2) total raw score	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

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

Trial Locations

Locations (45)

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

Universidade Federal de São Paulo, Escola Paulista de Medicina; 🇧🇷 São Paulo, Brazil

Faculdade de Medicina da Universidade de São Paulo - Departamento de Psiquiatria; 🇧🇷 São Paulo, Brazil

GSC CHU-LENVAL Centre ressource autisme; 🇫🇷 Nice, Alpes-Maritimes, France

Hôpitaux Universitaires de Strasbourg Service de Psychiatrie de l'Enfant et de l'Adolescent; 🇫🇷 Strasbourg, Alsace-Champagne-Ardenne-Lorraine, 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

Hôpital Robert Debré Service de Psychiatrie de l'enfant et de l'adolescent; 🇫🇷 Paris, Il De France, France

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