Bumetanide oral solution for the treatment of children and adolescents with autism spectrum disorder: Results from two randomized phase III studies / Joaquin FUENTES in Autism Research, 16-10 (October 2023)  

Public ISBD [article]  inAutism Research > 16-10 (October 2023) . - p.2021-2034 Titre : Bumetanide oral solution for the treatment of children and adolescents with autism spectrum disorder: Results from two randomized phase III studies Type de document : Texte imprimé et/ou numérique Auteurs : Joaquin FUENTES, Auteur ; Mara PARELLADA, Auteur ; Christina GEORGOULA, Auteur ; Guiomar OLIVEIRA, Auteur ; Stéphane MARRET, Auteur ; Véronique CRUTEL, Auteur ; Cristina ALBARRAN, Auteur ; Estelle LAMBERT, Auteur ; Pierre-François PÉNÉLAUD, Auteur ; Denis RAVEL, Auteur ; Yehezkel BEN ARI, Auteur Article en page(s) : p.2021-2034 Index. décimale : PER Périodiques Résumé : Abstract The efficacy and safety of bumetanide oral solution for the treatment of autism spectrum disorder (ASD) in children and adolescents was evaluated in two international, multi-center, randomized, double-blind, placebo-controlled phase III trials; one enrolled patients aged 7-17?years (SIGN 1 trial) and the other enrolled younger patients aged 2-6?years (SIGN 2). In both studies, patients were randomized to receive bumetanide oral solution twice daily (BID) or placebo BID during a 6-month double-blind treatment period. The primary endpoint was change in Childhood Autism Rating Scale 2 (CARS2) total raw score from baseline to Week 26. Key secondary endpoints included changes in Social Responsiveness Scale-2, Clinical Global Impression Scale, and Vineland Adaptive Behavior Scale. Each study enrolled 211 patients (bumetanide, n?=?107; placebo, n?=?104). Both studies were terminated early due to absence of any significant difference between bumetanide and placebo in the overall studied populations. In both studies, CARS2 total raw score decreased from baseline to Week 26 in the bumetanide and placebo groups, with no statistically significant difference between groups. No differences were observed between treatment groups for any of the secondary efficacy endpoints in either study. In both studies, treatment-emergent adverse events that occurred more frequently with bumetanide than placebo included thirst, polyuria, hypokalemia, and dry mouth. These large phase III trials failed to demonstrate a benefit of bumetanide for the treatment of pediatric ASD compared with placebo. 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. En ligne : https://doi.org/10.1002/aur.3005 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Bumetanide oral solution for the treatment of children and adolescents with autism spectrum disorder: Results from two randomized phase III studies [Texte imprimé et/ou numérique] / Joaquin FUENTES, Auteur ; Mara PARELLADA, Auteur ; Christina GEORGOULA, Auteur ; Guiomar OLIVEIRA, Auteur ; Stéphane MARRET, Auteur ; Véronique CRUTEL, Auteur ; Cristina ALBARRAN, Auteur ; Estelle LAMBERT, Auteur ; Pierre-François PÉNÉLAUD, Auteur ; Denis RAVEL, Auteur ; Yehezkel BEN ARI, Auteur . - p.2021-2034. in Autism Research > 16-10 (October 2023) . - p.2021-2034 Index. décimale : PER Périodiques Résumé : Abstract The efficacy and safety of bumetanide oral solution for the treatment of autism spectrum disorder (ASD) in children and adolescents was evaluated in two international, multi-center, randomized, double-blind, placebo-controlled phase III trials; one enrolled patients aged 7-17?years (SIGN 1 trial) and the other enrolled younger patients aged 2-6?years (SIGN 2). In both studies, patients were randomized to receive bumetanide oral solution twice daily (BID) or placebo BID during a 6-month double-blind treatment period. The primary endpoint was change in Childhood Autism Rating Scale 2 (CARS2) total raw score from baseline to Week 26. Key secondary endpoints included changes in Social Responsiveness Scale-2, Clinical Global Impression Scale, and Vineland Adaptive Behavior Scale. Each study enrolled 211 patients (bumetanide, n?=?107; placebo, n?=?104). Both studies were terminated early due to absence of any significant difference between bumetanide and placebo in the overall studied populations. In both studies, CARS2 total raw score decreased from baseline to Week 26 in the bumetanide and placebo groups, with no statistically significant difference between groups. No differences were observed between treatment groups for any of the secondary efficacy endpoints in either study. In both studies, treatment-emergent adverse events that occurred more frequently with bumetanide than placebo included thirst, polyuria, hypokalemia, and dry mouth. These large phase III trials failed to demonstrate a benefit of bumetanide for the treatment of pediatric ASD compared with placebo. 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. En ligne : https://doi.org/10.1002/aur.3005 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

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