Arbaclofen in fragile X syndrome: results of phase 3 trials.

ABSTRACT: BACKGROUND:Arbaclofen 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. METHODS:Two 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. RESULTS:A 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?

SUBMITTER: Berry-Kravis E 

PROVIDER: S-EPMC5467054 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature