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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.

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ClinicalTrials.gov Identifier: NCT03715153
Recruitment Status : Recruiting
First Posted : October 23, 2018
Last Update Posted : March 18, 2020
Sponsor:
Collaborator:
ADIR, a Servier Group company
Information provided by (Responsible Party):
Servier ( Institut de Recherches Internationales Servier )

Tracking Information
First Submitted Date  ICMJE October 12, 2018
First Posted Date  ICMJE October 23, 2018
Last Update Posted Date March 18, 2020
Actual Study Start Date  ICMJE October 4, 2018
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 18, 2018)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2018)
  • 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
  • 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
  • Vineland Adaptative Behaviour Scale II (VABS II) [ Time Frame: Change from baseline to 6 month ]
    Efficacy criterion Scale designated to measure adaptative behaviour
  • 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.
  • Abnormalities in 12-leads electrocardiogram (ECG) parameters [ Time Frame: Selection visit, Week004, Week008, Week012, Week026, Week030, Week034, Week038, Week052 ]
    Safety criterion
  • Renal ultrasound [ Time Frame: Selection visit, Week026, Week052 ]
    Safety criterion Assessment of the renal function
  • 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
  • Acceptability and palatability questionnaires [ Time Frame: Week026 ]
    Acceptability and palatability criterion Assessment of the ease of use to use the dosing device
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: October 18, 2018)
  • 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
  • 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
  • Vineland Adaptative Behaviour Scale II (VABS II) [ Time Frame: Change from baseline to 6 month ]
    Efficacy criterion Scale designated to measure adaptative behaviour
  • 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.
  • Electrocardiogram (ECG) [ Time Frame: Selection visit, Week004, Week008, Week012, Week026, Week030, Week034, Week038, Week052 ]
    safety criterion Assessment of heart activity
  • Renal ultrasound [ Time Frame: Selection visit, Week026, Week052 ]
    Safety criterion Assessment of the renal function
  • 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
  • Acceptability and palatability questionnaires [ Time Frame: Week026 ]
    Acceptability and palatability criterion Assessment of the ease of use to use the dosing device
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
Official Title  ICMJE 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.
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Condition  ICMJE Autism Spectrum Disorder (ASD)
Intervention  ICMJE
  • Drug: BUMETANIDE/S95008
    Oral solution dosed at 0.5 mg/mL Taken twice daily.
  • Drug: PLACEBO
    Oral solution Taken twice daily.
Study Arms  ICMJE
  • Experimental: BUMETANIDE/S95008
    Intervention: Drug: BUMETANIDE/S95008
  • Placebo Comparator: PLACEBO
    Intervention: Drug: PLACEBO
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 18, 2018)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2021
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 6 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Institut de Recherches Internationales Servier Clinical Studies Department +33 1 55 72 43 66 clinical.trial.management@servier.com
Listed Location Countries  ICMJE Australia,   Brazil,   Czechia,   France,   Germany,   Hungary,   Italy,   Poland,   Portugal,   Slovakia,   Spain,   United Kingdom,   United States
Removed Location Countries Netherlands
 
Administrative Information
NCT Number  ICMJE NCT03715153
Other Study ID Numbers  ICMJE CL3-95008-002
2017-004420-30 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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.

They can ask for all interventional clinical studies:

  • submitted for new medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
  • Where Servier or an affiliate are the Marketing Authorization Holders (MAH). The date of the first Marketing Authorization of the new médicine (or the new indication) in one of the EEA Member States will be considered within this scope.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: 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.
URL: http://clinicaltrials.servier.com/
Responsible Party Servier ( Institut de Recherches Internationales Servier )
Study Sponsor  ICMJE Institut de Recherches Internationales Servier
Collaborators  ICMJE ADIR, a Servier Group company
Investigators  ICMJE Not Provided
PRS Account Servier
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP