A Randomized, Placebo-Controlled Trial of Guanfacine Extended Release in Adolescents With Attention-Deficit/Hyperactivity Disorder.
OBJECTIVE
Despite the continuity of attention-deficit/hyperactivity disorder (ADHD) into adolescence, little is known regarding use of nonstimulants to treat ADHD in adolescents. This phase 3 trial evaluated the safety and efficacy of guanfacine extended release (GXR) in adolescents with ADHD.


METHODS
This 13-week, multicenter, randomized, double-blind, placebo-controlled trial evaluated once-daily GXR (1-7 mg per day) in adolescents with ADHD aged 13 to 17 years. The primary endpoint was the change from baseline in the ADHD Rating Scale-IV (ADHD-RS-IV) total score; key secondary endpoints included scores from the Clinical Global Impressions-Severity of Illness (CGI-S), and Learning and School domain and Family domain scores from the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) at week 13.


RESULTS
A total of 314 participants were randomized (GXR, n = 157; placebo, n = 157). The majority of participants received optimal doses of 3, 4, 5, or 6 mg (30 [22.9%], 26 [19.8%], 27 [20.6%], or 24 [18.3%] participants, respectively), with 46.5% of participants receiving an optimal dose above the currently approved maximum dose limit of 4 mg. Participants receiving GXR showed improvement in ADHD-RS-IV total score compared with placebo (least-squares mean score change, -24.55 [GXR] versus -18.53 [placebo]; effect size, 0.52; p <.001). More participants on GXR also showed significant improvement in CGI-S scores compared with placebo (50.6% versus 36.1%; p = .010). There was no statistically significant difference between treatments at week 13 in the 2 WFIRS-P domains. Most treatment-emergent adverse events were mild to moderate, with sedation-related events reported most commonly.


CONCLUSIONS
GXR was associated with statistically significant improvements in ADHD symptoms in adolescents. GXR was well tolerated, with no new safety signals reported.


BACKGROUND
Dose-Optimization in Adolescents Aged 13-17 Diagnosed With Attention-Deficit/Hyperactivity Disorder (ADHD) Using Extended-Release Guanfacine HCl; http://ClinicalTrials.gov/; NCT01081132.
Massachusetts General Hospital, Boston. Electronic address: twilens@partners.org.
Timothy E
TE
Wilens
Former employees of Shire, Wayne, PA; Neurovance, Inc., Cambridge, MA.
Brigitte
B
Robertson
Former employees of Shire, Wayne, PA; GlaxoSmithKline, King of Prussia, PA.
Vanja
V
Sikirica
CNS Healthcare, Orlando, FL.
Linda
L
Harper
Rochester Center for Behavioral Medicine, Rochester Hills, MI.
Joel L
JL
Young
Former employees of Shire, Wayne, PA; AstraZeneca, Cambridge, UK.
Ralph
R
Bloomfield
Former employees of Shire, Wayne, PA; Independent statistician, Maidenhead, UK.
Andrew
A
Lyne
Former employees of Shire, Wayne, PA.
Gail
G
Rynkowski
Florida Clinical Research Center, LLC, Bradenton, FL.
Andrew J
AJ
Cutler
D000293:Adolescent; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000067290:Behavior Rating Scale; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D016316:Guanfacine / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D012574:Schools; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014481:United States
D058647:Adrenergic alpha-2 Receptor Agonists; D003692:Delayed-Action Preparations; D016316:Guanfacine
GXR; attention-deficit/hyperactivity disorder; guanfacine; nonstimulants