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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03715153




Registration number
NCT03715153
Ethics application status
Date submitted
12/10/2018
Date registered
23/10/2018
Date last updated
5/06/2023

Titles & IDs
Public title
Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
Scientific 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.
Secondary ID [1] 0 0
2017-004420-30
Secondary ID [2] 0 0
CL3-95008-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Autism Spectrum Disorder (ASD) 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Autistic spectrum disorders
Mental Health 0 0 0 0
Other mental health disorders
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BUMETANIDE (S95008) for week 0 - 26
Treatment: Drugs - PLACEBO for week 0 - 26
Treatment: Drugs - Open-Label BUMETANIDE (S95008) for weeks 26 - 52

Experimental: 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.

Placebo Comparator: 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.


Treatment: Drugs: BUMETANIDE (S95008) for week 0 - 26
Oral solution dosed at 0.5 mg/mL Taken twice daily.

Treatment: Drugs: PLACEBO for week 0 - 26
Oral solution Taken twice daily.

Treatment: Drugs: Open-Label BUMETANIDE (S95008) for weeks 26 - 52
Oral solution dosed at 0.5 mg/mL Taken twice daily.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Childhood Autism Rating Scale, Second Edition (CARS2) Total Raw Score
Timepoint [1] 0 0
Change from baseline to Week 26
Secondary outcome [1] 0 0
Social Responsiveness Scale, Second Edition (SRS-2) Total Raw Score
Timepoint [1] 0 0
Change from baseline to Week 26
Secondary outcome [2] 0 0
Clinical Global Impression - Global Improvement (CGI-I) Score
Timepoint [2] 0 0
At Week 26
Secondary outcome [3] 0 0
Vineland Adaptative Behaviour Scale II (VABS II)
Timepoint [3] 0 0
Change from baseline to Week 26
Secondary outcome [4] 0 0
Number of Patients With Abnormalities in 12-leads Electrocardiogram (ECG) Parameters
Timepoint [4] 0 0
Week 26
Secondary outcome [5] 0 0
Columbia-Suicide Severity Scale Children's Version (C-SSRS-C)
Timepoint [5] 0 0
Week 26
Secondary outcome [6] 0 0
Acceptability and Palatability Questionnaires - Only Descriptive Analyses
Timepoint [6] 0 0
Week 26
Secondary outcome [7] 0 0
Paediatric Quality of Life Inventory (PedsQL) Questionnaire
Timepoint [7] 0 0
Change from baseline to week 26
Secondary outcome [8] 0 0
Number of Participants Experiencing at Least 1 Treatment Emergent Adverse Event (TEAE)
Timepoint [8] 0 0
through week 52

Eligibility
Key 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.
Minimum age
2 Years
Maximum age
6 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/10/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/10/2021
Sample size
Target
Accrual to date
Final
211
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
The Royal Children's Hospital Melbourne - Parkville
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New York
Country [2] 0 0
Brazil
State/province [2] 0 0
Curitiba
Country [3] 0 0
Brazil
State/province [3] 0 0
Fortaleza
Country [4] 0 0
Brazil
State/province [4] 0 0
Joinville
Country [5] 0 0
Brazil
State/province [5] 0 0
Passo Fundo
Country [6] 0 0
Brazil
State/province [6] 0 0
São Paulo
Country [7] 0 0
Czechia
State/province [7] 0 0
Ostrava
Country [8] 0 0
Czechia
State/province [8] 0 0
Brno
Country [9] 0 0
Czechia
State/province [9] 0 0
Praha
Country [10] 0 0
France
State/province [10] 0 0
Alpes-Maritimes
Country [11] 0 0
France
State/province [11] 0 0
Alsace-Champagne-Ardenne-Lorraine
Country [12] 0 0
France
State/province [12] 0 0
Auvergne Rhone Alpes
Country [13] 0 0
France
State/province [13] 0 0
Auvergne-Rhône-Alpes
Country [14] 0 0
France
State/province [14] 0 0
Ile De France
Country [15] 0 0
France
State/province [15] 0 0
Normandie
Country [16] 0 0
France
State/province [16] 0 0
Nouvelle Aquitaine
Country [17] 0 0
France
State/province [17] 0 0
Nouvelle-Aquitaine
Country [18] 0 0
Hungary
State/province [18] 0 0
Budapest
Country [19] 0 0
Hungary
State/province [19] 0 0
Gyula
Country [20] 0 0
Hungary
State/province [20] 0 0
Szeged
Country [21] 0 0
Italy
State/province [21] 0 0
Lombardia
Country [22] 0 0
Italy
State/province [22] 0 0
Sardegna
Country [23] 0 0
Italy
State/province [23] 0 0
Sicilia
Country [24] 0 0
Italy
State/province [24] 0 0
Toscana
Country [25] 0 0
Poland
State/province [25] 0 0
Gdansk
Country [26] 0 0
Poland
State/province [26] 0 0
Lodz
Country [27] 0 0
Poland
State/province [27] 0 0
Warszawa
Country [28] 0 0
Portugal
State/province [28] 0 0
Coimbra
Country [29] 0 0
Slovakia
State/province [29] 0 0
Bratislava
Country [30] 0 0
Slovakia
State/province [30] 0 0
Košice
Country [31] 0 0
Spain
State/province [31] 0 0
Barcelona
Country [32] 0 0
Spain
State/province [32] 0 0
Guipuzcoa
Country [33] 0 0
Spain
State/province [33] 0 0
Madrid
Country [34] 0 0
Spain
State/province [34] 0 0
Alicante
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Colchester
Country [36] 0 0
United Kingdom
State/province [36] 0 0
London
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Other
Name
Institut de Recherches Internationales Servier
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
ADIR, a Servier Group company
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03715153
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03715153