Effect of CX516, an AMPA-modulating compound, on cognition and behavior in fragile X syndrome: A controlled trial

Elizabeth Berry-Kravis, Sue Ellen Krause, Sandra S. Block, Steve Guter, Joanne Wuu, Sue Leurgans, Penelope Decle, Kristina Potanos, Edwin Cook, Jeff Salt, Dominick Maino, Dahlia Weinberg, Rebecca Lara, Tristan Jardini, Jennifer Cogswell, Steven A. Johnson, Randi Hagerman

Research output: Contribution to journalArticlepeer-review

124 Scopus citations


A Phase II, 4-week randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the safety and efficacy of the Ampakine compound CX516 as a potential treatment for the underlying disorder in fragile X syndrome (FXS). After baseline screening, subjects with FXS (n = 49) underwent a 1-week placebo lead-in and then were randomized to study drug or placebo for a 4-week period. Cognitive and behavioral outcome measures were administered prior to treatment, at the end of treatment, and 2 weeks posttreatment. There were minimal side effects, no significant changes in safety parameters, and no serious adverse events. There was a 12.5% frequency of allergic rash in the CX516 group and 1 subject developed a substantial rash. There was also no significant improvement in memory, the pri-mary outcome measure, or in secondary measures of language, attention/executive function, behavior, and overall functioning in CX516-treated subjects compared to placebo. This study did demonstrate that many outcome measures were reproducible in this test-retest setting for the FXS population, yet some were too difficult or variable. Adult subjects with FXS were able to complete an intensive clinical trial, and some valid outcome measures were identified for future FXS trial design. Problems with potency of CX516 in other studies have suggested dosing may have been inadequate for therapeutic effect and thus it remains unclear whether modulation of AMPA-mediated neurotransmission is a viable therapeutic strategy for the treatment of FXS.

Original languageEnglish (US)
Pages (from-to)525-540
Number of pages16
JournalJournal of Child and Adolescent Psychopharmacology
Issue number5
StatePublished - Oct 2006
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Psychiatry and Mental health
  • Pharmacology (medical)


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