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Improvement of Daily Living Skills in Adolescents and Adults with Fragile X Syndrome Following MDX (Metadoxine Extended Release) Administration
Objectives: To fully characterize the effects of MDX on the Vineland-II DLS in FXS.
Methods: Subjects enrolled in the study were males and females with molecular diagnosis of FXS, (≥200 CGG repeats, in FMR1) 14 to 55 years, with a score ≥12 on the inattentive subscale of the ADHD RS-IV. Improvements in the group assigned to MDX, in comparison with the placebo group, with a secondary efficacy assessment, the Vineland Adaptive Behavior Scale, Expanded Interview Form, Second Edition (Vineland-II) DLS were characterized in detail by using item analysis and correlating results with other outcomes.
Results: 62 subjects were randomized (MDX 30; placebo 32). The primary analysis, the MMRM LS mean change from baseline to week6/early termination in the ITT population was significant on the DLS domain standard score (p=0.04) and the community subdomain v-scale score (p=0.004), and was not significant for the personal and domestic subdomain v-scale scores. These results were strengthened when the ITT population was limited in a post-hoc analysis to subjects with normalized IQ from 40-85 and ages 14-40.
Analysis of individual items in the DLS domain demonstrated significant effects (p<0.05) for several questions such as: seeks medical help in emergencies, plans and/or organized daily work, and carries out multi-step tasks. For most of these items, the MDX placebo difference in the mean change from baseline to week 6/ET was 0.5 to 1, demonstrating a categorical improvement. Items from objective secondary measures in the trial directly assessing the subject (KiTAP Distractibility and Go/No-Go computerized tests, and RBANS-List Learning), produced supportive correlations (r>0.25, p<0.05) with improvements on the DLS domain.
Conclusions: MDX demonstrated a statistically significant effect on the Vineland-II DLS domain in FXS. Item analyses suggested clinically meaningful changes in areas related to daily living skills, and correlations with other objective outcomes strengthened the effect.