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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03715153
Recruitment Status : Active, not recruiting
First Posted : October 23, 2018
Last Update Posted : January 20, 2021
ADIR, a Servier Group company
Information provided by (Responsible Party):
Servier ( Institut de Recherches Internationales Servier )

Brief Summary:
The purpose of this study is to evaluate the efficacity and the safety of bumetanide/S95008 in the improvement of Autism Spectrum Disorder core symptoms.

Condition or disease Intervention/treatment Phase
Autism Spectrum Disorder (ASD) Drug: BUMETANIDE/S95008 Drug: PLACEBO Phase 3

Detailed Description:
The present study (CL3-95008-002) will be performed in children from 2 to less than 7 years old presenting with ASD. A 6-month double-blind treatment period will be performed in which efficacy and safety of bumetanide 0.5mg BID will be assessed versus placebo. This double-blind period will be followed by a 6-month open label treatment period of bumetanide 0.5mg BID in which long term safety will be evaluated.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 211 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 6-month, randomized, double-blind, placebo-controlled, parallel groups followed by an open label active 6-month treatment period with bumetanide.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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.
Actual Study Start Date : October 4, 2018
Estimated Primary Completion Date : June 15, 2021
Estimated Study Completion Date : September 20, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Bumetanide

Arm Intervention/treatment
Experimental: BUMETANIDE/S95008 Drug: BUMETANIDE/S95008
Oral solution dosed at 0.5 mg/mL Taken twice daily.

Placebo Comparator: PLACEBO Drug: PLACEBO
Oral solution Taken twice daily.

Primary Outcome Measures :
  1. Childhood Autism Rating Scale, Second Edition (CARS2) total raw score [ Time Frame: 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 :
  1. Social Responsiveness Scale, Second Edition (SRS-2) total raw score [ Time Frame: Change from baseline to 6 month ]
    Efficacy criterion 65 items scale measuring symptoms associated with autism

  2. Clinical Global Impression - Global Improvement (CGI-I) score [ Time Frame: At 6 months ]
    Efficacy criterion Scale which assesses the severity of the illness and the global improvement of the patient Under study treatment

  3. Vineland Adaptative Behaviour Scale II (VABS II) [ Time Frame: Change from baseline to 6 month ]
    Efficacy criterion Scale designated to measure adaptative behaviour

  4. Adverse Event and Pediatric Adverse Event Rating Scale (PAERS) [ Time Frame: On average of 52 weeks ]
    Safety criterion Inventory report used to identify signs/symptoms experienced by the patient since the study treatment initiation.

  5. Abnormalities in 12-leads electrocardiogram (ECG) parameters [ Time Frame: Selection visit, Week004, Week008, Week012, Week026, Week030, Week034, Week038, Week052 ]
    Safety criterion

  6. Renal ultrasound [ Time Frame: Selection visit, Week026, Week052 ]
    Safety criterion Assessment of the renal function

  7. Columbia-Suicide severity scale Children's version (C-SSRS-C) [ Time Frame: Week000/Week012/Week026/Week038/Week052 ]
    Scale which assesses suicidal ideation and suicidal behaviour

  8. Acceptability and palatability questionnaires [ Time Frame: Week026 ]
    Acceptability and palatability criterion Assessment of the ease of use to use the dosing device

  9. Paediatric Quality of Life Inventory (PedsQL) questionnaire [ Time Frame: Week000/Week004/Week012/v026/Week030/Week038/Week052 ]
    Quality of Life questionnaire Assessment of parent/legal representative perception of patient health related quality of life

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 6 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03715153

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Sponsors and Collaborators
Institut de Recherches Internationales Servier
ADIR, a Servier Group company
Additional Information:
Study Data/Documents: Individual Participant Data Set  This link exits the site

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Responsible Party: Institut de Recherches Internationales Servier Identifier: NCT03715153    
Other Study ID Numbers: CL3-95008-002
2017-004420-30 ( EudraCT Number )
First Posted: October 23, 2018    Key Record Dates
Last Update Posted: January 20, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

  • used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
  • where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

  • sponsored by Servier
  • with a first patient enrolled as of 1 January 2004 onwards
  • for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders
Natriuretic Agents
Physiological Effects of Drugs
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action