1. Arbaclofen in fragile X syndrome: results of phase 3 trials
- Author
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Berry-Kravis, Elizabeth, Hagerman, Randi, Visootsak, Jeannie, Budimirovic, Dejan, Kaufmann, Walter E, Cherubini, Maryann, Zarevics, Peter, Walton-Bowen, Karen, Wang, Paul, Bear, Mark F, and Carpenter, Randall L
- Subjects
Clinical Trials and Supportive Activities ,Intellectual and Developmental Disabilities (IDD) ,Rare Diseases ,Mental Health ,Fragile X Syndrome ,Patient Safety ,Clinical Research ,Pediatric ,Brain Disorders ,Behavioral and Social Science ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Fragile X syndrome ,Arbaclofen ,GABA agonist ,FMR1 ,Targeted treatment ,Neurodevelopmental disorder ,Neurosciences ,Psychology - Abstract
BackgroundArbaclofen improved multiple abnormal phenotypes in animal models of fragile X syndrome (FXS) and showed promising results in a phase 2 clinical study. The objective of the study is to determine safety and efficacy of arbaclofen for social avoidance in FXS.MethodsTwo phase 3 placebo-controlled trials were conducted, a flexible dose trial in subjects age 12-50 (209FX301, adolescent/adult study) and a fixed dose trial in subjects age 5-11 (209FX302, child study). The primary endpoint for both trials was the Social Avoidance subscale of the Aberrant Behavior Checklist-Community Edition, FXS-specific (ABC-CFX). Secondary outcomes included other ABC-CFX subscale scores, Clinical Global Impression-Improvement (CGI-I), Clinical Global Impression-Severity (CGI-S), and Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) Socialization domain score.ResultsA total 119 of 125 randomized subjects completed the adolescent/adult study (n = 57 arbaclofen, 62 placebo) and 159/172 completed the child study (arbaclofen 5 BID n = 38; 10 BID n = 39; 10 TID n = 38; placebo n = 44). There were no serious adverse events (AEs); the most common AEs included somatic (headache, vomiting, nausea), neurobehavioral (irritability/agitation, anxiety, hyperactivity), decreased appetite, and infectious conditions, many of which were also common on placebo. In the combined studies, there were 13 discontinuations (n = 12 arbaclofen, 1 placebo) due to AEs (all neurobehavioral). The adolescent/adult study did not show benefit for arbaclofen over placebo for any measure. In the child study, the highest dose group showed benefit over placebo on the ABC-CFX Irritability subscale (p = 0.03) and Parenting Stress Index (PSI, p = 0.03) and trends toward benefit on the ABC-CFX Social Avoidance and Hyperactivity subscales (both p
- Published
- 2017