bumetanide (S95008) / Servier, Neurochlore - LARVOL DELTA

Exit interviews from two randomised placebo-controlled phase 3 studies with caregivers of young children with autism spectrum disorder. (PubMed, Front Child Adolesc Psychiatry) - P3 | "The exit interviews provided a rich source of qualitative data, allowing a deeper understanding of caregivers' and patients' experience of the disease and allowing us to understand what constitutes a meaningful change. These data also helped identify important experiences that may inform the patient-reported outcome measurement strategy for future trials in ASD."

Interview • Journal • P3 data • Autism Spectrum Disorder • Genetic Disorders

A Double-Blind, Randomized, Placebo-Controlled Trial of Bumetanide in Parkinson's Disease. (PubMed, Mov Disord) - "There was no evidence in this study that bumetanide has efficacy in improving motor symptoms of PD."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Bumetanide oral solution for the treatment of children and adolescents with autism spectrum disorder: Results from two randomized phase III studies. (PubMed, Autism Res) - P3 | "Consequently, the sponsor has discontinued the development of bumetanide for the treatment of this condition. Trial registration: https://clinicaltrials.gov: SIGN 1: NCT03715166; SIGN 2: NCT03715153."

Clinical • Journal • P3 data • Autism Spectrum Disorder • Genetic Disorders • Pediatrics • Xerostomia

The early excitatory action of striatal cholinergic-GABAergic microcircuits conditions the subsequent GABA inhibitory shift. (PubMed, Commun Biol) - "Early chronic treatment with the NKCC1 antagonist bumetanide to evoke premature GABAergic inhibitions from P4 to P8, prevented the GABA polarity shift and corticostriatal pause response at control postnatal days. We propose that early excitatory cholinergic-GABAergic microcircuits are instrumental in the maturation of GABAergic inhibition."

Journal

A Wholistic View of How Bumetanide Attenuates Autism Spectrum Disorders. (PubMed, Cells) - "We suggest that a more holistic view of ASD and other disorders is warranted to account for the multiple sites impacted by the original intra-uterine insult. From this perspective, large-spectrum active repositioned drugs that act centrally and peripherally might constitute a useful approach to treating these disorders."

Journal • Alzheimer's Disease • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Genetic Disorders • Movement Disorders • Parkinson's Disease • Psychiatry • SLC12A2

A Phase III Study of Bumetanide Oral Liquid Formulation for the Treatment of Children and Adolescents Aged Between 7 and 17 Years with Autism Spectrum Disorder (SIGN 1 Trial): Participant Baseline Characteristics. (PubMed, Child Psychiatry Hum Dev) - "Mean CARS2 score was 40.1 (4.9) and mean Social Responsiveness Scale score was 116.7 (23.4). Final study results will provide data on efficacy and safety of bumetanide in autistic children and adolescents."

Journal • P3 data • Autism Spectrum Disorder • Genetic Disorders • Pediatrics

The GABA Polarity Shift and Bumetanide Treatment: Making Sense Requires Unbiased and Undogmatic Analysis. (PubMed, Cells) - "Here, we reply to the recent reviews by Kaila et al. stressing that the GABA polarity shift is solidly accepted by the scientific community as a major discovery to understand brain development and that bumetanide has shown promising effects in clinical trials."

Journal • Review • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Fragile X Syndrome • Genetic Disorders • Movement Disorders • Psychiatry

Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder. (clinicaltrials.gov) - P3; N=211; Terminated; Sponsor: Institut de Recherches Internationales Servier; Trial completion date: Sep 2022 ➔ Oct 2021; Active, not recruiting ➔ Terminated; Trial primary completion date: Jun 2021 ➔ Oct 2021; The 6-month efficacy analysis did not show any significant difference between bumetanide versus placebo in the treatment of ASD in the overall studied population. No unexpected safety concerns were identified.

Clinical • Trial completion date • Trial primary completion date • Trial termination • Autism Spectrum Disorder • Genetic Disorders

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 (clinicaltrials.gov) - P3; N=211; Terminated; Sponsor: Institut de Recherches Internationales Servier; Active, not recruiting ➔ Terminated; The 6-month efficacy analysis did not show any significant difference between bumetanide versus placebo in the treatment of ASD in the overall studied population. No unexpected safety concerns were identified.

Clinical • Trial termination • Autism Spectrum Disorder • Genetic Disorders

"End of the line for @Servier and Neurochlore's #autism hope bumetanide after it fails across the board in a pair of phase 3 trials #pharma #ASD https://t.co/eHQ5K4EKh7" (@pharmaphorum)

Autism Spectrum Disorder • Genetic Disorders

[VIRTUAL] The CARS Scale to Assess Pharmacological Therapies in Autism Spectrum Disorder- A Targeted Literature Review (ISPOR 2021) - "Together, the studies focused on a total of 9 pharmacological interventions, including secretin, risperidone and bumetanide...CONCLUSIONS The CARS was used in a quarter of the few studies that assessed a pharmacological intervention in ASD. Despite this and the recent recognition by the EMA of the CARS merit in assessing effect on ASD core symptoms, our review indicates the need to define a clinically meaningful treatment response and a MCID for the CARS."

Review • Autism Spectrum Disorder • Genetic Disorders • Pediatrics

Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder. (clinicaltrials.gov) - P3; N=211; Active, not recruiting; Sponsor: Institut de Recherches Internationales Servier; Recruiting ➔ Active, not recruiting; Trial completion date: Apr 2022 ➔ Sep 2022

Clinical • Enrollment closed • Trial completion date • Autism Spectrum Disorder • Genetic Disorders

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 (clinicaltrials.gov) - P3; N=211; Active, not recruiting; Sponsor: Institut de Recherches Internationales Servier; Trial completion date: May 2021 ➔ Dec 2021; Trial primary completion date: May 2021 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Autism Spectrum Disorder • Genetic Disorders

[VIRTUAL] Bumetanide Improves Social Behavior in the BTBR Mouse Model of Autism (INSAR 2020) - "Acute bumetanide administration dose-dependently attenuated the deficit in sociability, an autism-relevant symptom, displayed by BTBR mice. Globally, the present study shows for the first time a postnatal effect of bumetanide in a relevant ASD animal model, supporting its use in clinical trials and suggesting bumetanide as a promising drug to enhance sociability deficits in ASD patients."

Preclinical • Autism Spectrum Disorder • Genetic Disorders • Pediatrics

Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder. (clinicaltrials.gov) - P3; N=200; Recruiting; Sponsor: Institut de Recherches Internationales Servier; Trial completion date: Apr 2021 ➔ Apr 2022; Trial primary completion date: Apr 2021 ➔ Sep 2021

Clinical • Trial completion date • Trial primary completion date • Autism Spectrum Disorder • Genetic Disorders

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 (clinicaltrials.gov) - P3; N=200; Active, not recruiting; Sponsor: Institut de Recherches Internationales Servier; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed