title: Exploratory randomized clinical study of pagoclone in persistent developmental stuttering: the EXamining Pagoclone for peRsistent dEvelopmental Stuttering Study.
abstract: BACKGROUND
  Stuttering is a speech disorder in which the flow of speech is disrupted by repetitions, prolongation, and blocks of sounds, syllables, or words. No pharmacological treatments are approved for use in stuttering, and the most common form of treatment is speech therapy. This study was designed to assess the safety, tolerability, and effectiveness of pagoclone during 8 weeks of double-blind treatment followed by a 1-year open-label extension in patients who stutter.
  
  
  METHODS
  An 8-week, multicenter, parallel-group, 2-arm, randomized (ratio 2:1 pagoclone-placebo), double-blind study with a 1-year open-label extension conducted at 16 US centers, including men and women aged 18 to 65 years who developed stuttering before 8 years of age. Twice-daily dosing with pagoclone (n = 88 patients) or matching placebo (n = 44 patients), with primary and secondary efficacy variables defined a priori, including Stuttering Severity Instrument Version 3 outcomes, clinician global impressions of improvement, and the change in the percentage of syllables stuttered.
  
  
  RESULTS
  Pagoclone produced an average 19.4% reduction in percentage of syllables stuttered compared with 5.1% reduction for placebo. During open-label treatment, a 40% reduction in the percent syllables stuttered was observed after 1 year of treatment with pagoclone. The most commonly reported adverse event during double-blind treatment was headache (12.5% pagoclone patients, 6.8% placebo patients).
  
  
  CONCLUSIONS
  Pagoclone was effective in reducing symptoms of stuttering and was well tolerated. In light of its favorable tolerability profile, as well as consistency of effects across multiple efficacy variables, pagoclone may have potential as a pharmacological treatment of stuttering.
  
  
  CONCLUSIONS
  The main limitation of this study was the adequacy of the number of subjects who participated because this study was conducted as a pilot investigation. Furthermore, as this condition waxes and wanes, the assessment of stuttering within the clinic setting may not be an adequate reflection of the stuttering of the patients within the community.
authors.affiliation: University of California, Irvine School of Medicine, Orange, CA 92868, USA. gerald.maguire@uci.edu
authors.forename: Gerald
authors.initials: G
authors.lastname: Maguire
authors.forename: David
authors.initials: D
authors.lastname: Franklin
authors.forename: Nick G
authors.initials: NG
authors.lastname: Vatakis
authors.forename: Elena
authors.initials: E
authors.lastname: Morgenshtern
authors.forename: Timothey
authors.initials: T
authors.lastname: Denko
authors.forename: J Scott
authors.initials: JS
authors.lastname: Yaruss
authors.forename: Crystal
authors.initials: C
authors.lastname: Spotts
authors.forename: Larry
authors.initials: L
authors.lastname: Davis
authors.forename: Aaron
authors.initials: A
authors.lastname: Davis
authors.forename: Peter
authors.initials: P
authors.lastname: Fox
authors.forename: Poonam
authors.initials: P
authors.lastname: Soni
authors.forename: Michael
authors.initials: M
authors.lastname: Blomgren
authors.forename: Andrew
authors.initials: A
authors.lastname: Silverman
authors.forename: Glyndon
authors.initials: G
authors.lastname: Riley
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D054333:Drug Partial Agonism; D005260:Female; D058785:GABA-A Receptor Agonists; D006801:Humans; D054833:Isoindoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009287:Naphthyridines / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D013342:Stuttering / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D058785:GABA-A Receptor Agonists; D054833:Isoindoles; D009287:Naphthyridines; C447412:pagoclone