The long-term tolerability and efficacy of armodafinil in patients with excessive sleepiness associated with treated obstructive sleep apnea, shift work disorder, or narcolepsy: an open-label extension study.
OBJECTIVE
Armodafinil is a wakefulness-promoting medication. Its efficacy and tolerability have been established in 12-week studies of patients with excessive sleepiness (ES) associated with treated obstructive sleep apnea (OSA), shift work disorder (SWD), or narcolepsy. This study evaluated the tolerability and efficacy of armodafinil for > or = 12 months.


METHODS
Patients with ES associated with treated OSA, SWD, or narcolepsy who completed one of four 12-week, double-blind studies were eligible for this multicenter, open-label study of > or = 12 months' duration of treatment with armodafinil (50 to 250 mg/day). Adverse events and other criteria of tolerability were monitored throughout the study. Efficacy assessments included the Clinical Global Impression of Change (CGI-C), Brief Fatigue Inventory (BFI), and Epworth Sleepiness Scale (ESS).


RESULTS
Of 743 enrolled patients (474 with treated OSA, 113 with SWD, and 156 with narcolepsy), 57% of patients (420/743) completed 12 months or more of treatment. Discontinuations due to adverse events occurred in 13% of patients (95/743) during the initial 12-month period. Throughout the > or = 12-month study, adverse events were generally of mild-to-moderate intensity; headache (25% [180/731]), nasopharyngitis (17% [123/731]), and insomnia (14% [99/731]) were the most common. Modest increases were observed in vital sign measurements (blood pressure [3.6/2.3 mm Hg], heart rate [6.7 beats per minute]) across all patient groups; most of the changes occurred by month 3. Improvements from baseline in efficacy assessments started at month 1 and were maintained throughout the study.


CONCLUSIONS
Armodafinil remained effective and was generally well tolerated. Increased monitoring of blood pressure may be appropriate in patients on armodafinil. Armodafinil represents an option for long-term treatment of patients with ES associated with treated OSA, SWD, or narcolepsy.
Black
Jed E
JE
Actelion Pharmaceuticals, Allschwil, Switzerland. jedblack@stanford.edu
Hull
Steven G
SG
Tiller
Jane
J
Yang
Ronghua
R
Harsh
John R
JR
D000328:Adult; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D009290:Narcolepsy / Q000188:drug therapy*; D009304:Nasopharyngitis / Q000139:chemically induced; D020181:Sleep Apnea, Obstructive / Q000188:drug therapy*; D020178:Sleep Disorders, Circadian Rhythm / Q000188:drug therapy*; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced; D013995:Time; D016896:Treatment Outcome; D014851:Wakefulness / Q000187:drug effects*
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil