Exploratory randomized clinical study of pagoclone in persistent developmental stuttering: the EXamining Pagoclone for peRsistent dEvelopmental Stuttering Study.
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.
Maguire
Gerald
G
University of California, Irvine School of Medicine, Orange, CA 92868, USA. gerald.maguire@uci.edu
Franklin
David
D
Vatakis
Nick G
NG
Morgenshtern
Elena
E
Denko
Timothey
T
Yaruss
J Scott
JS
Spotts
Crystal
C
Davis
Larry
L
Davis
Aaron
A
Fox
Peter
P
Soni
Poonam
P
Blomgren
Michael
M
Silverman
Andrew
A
Riley
Glyndon
G
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
D058785:GABA-A Receptor Agonists; D054833:Isoindoles; D009287:Naphthyridines; C447412:pagoclone