BACKGROUND: Some patients with obstructive sleep apnea/hypopnea syndrome 
(OSA/HS) experience excessive sleepiness (ES) that might not resolve with nasal 
continuous positive airway pressure (nCPAP) treatment.
OBJECTIVE: The aim of the present study was to assess the efficacy and 
tolerability of armodafinil 150 or 250 mg QD when used as adjunctive treatment 
for residual ES associated with OSA/HS in patients who are adherent to nCPAP 
therapy.
METHODS: This 12-week, multicenter, double-blind, randomized, placebo-controlled 
study was conducted at 37 centers in the United States and Canada. Male and 
female patients aged 18 to 65 years with residual ES associated with OSA/HS were 
enrolled. Patients were randomly assigned to receive armodafinil 150 or 250 mg 
or placebo PO QD for 12 weeks. Assessments were conducted at baseline and study 
weeks 4, 8, and 12 and included the Maintenance of Wakefulness Test (MWT) to 
determine wakefulness, the Clinical Global Impression of Change (CGI-C) to 
determine improvement in clinical condition, the Epworth Sleepiness Scale (ESS) 
to determine patient-estimated wakefulness, the Brief Fatigue Inventory (BFI) to 
determine global fatigue, and the Cognitive Drug Research computerized 
assessment battery. To distinguish between earlier and later effects, sleep 
latencies, assessed using the MWT, were averaged across the first 4 (9 and 11 
AM, and 1 and 3 PM) and last 3 (3, 5, and 7 PM) tests. Tolerability assessments 
included monitoring of adverse events (AEs), clinical laboratory tests, vital 
sign measurements, and electrocardiography.
RESULTS: A total of 395 patients were enrolled in the study (armodafinil 150 
mg/d, 133; armodafinil 250 mg/d, 131; placebo, 131); 392 received >or=1 dose of 
study drug (armodafinil 150 mg/d, 131; armodafinil 250 mg/d, 131; placebo, 130). 
The armodafinil and placebo groups were well matched with regard to age (mean 
[SD], 49.2 [8.9] vs 50.1 [9.4] years), sex (71 vs 69% men), race (84% vs 87% 
white), and body weight (mean [SD], 110.3 [24.9] vs 111.9 [24.0] kg). At the 
final visit, the mean (SD) change from baseline in MWT sleep latency across the 
morning and afternoon was significantly greater in the armodafinil combined 
group compared with the placebo group (+1.9 [7.3] vs 1.7 [8.6] minutes; P < 
0.001). Also at the final visit, the proportions of patients who showed at least 
minimal improvement on the CGI-C, and the mean (SD) changes from baseline in ESS 
and BFI scores, were significantly greater in the armodafinil group compared 
with those in the placebo group (72% vs 37%, -5.5 [5.0] vs -3.3 [4.7], and -1.2 
[2.2] vs -0.6 [2.0], respectively; P < 0.001, P < 0.001, and P < 0.01, 
respectively). No significant effects on nighttime sleep, as assessed using 
polysomnography, were found with armodafinil. AEs reported in the armodafinil 
combined and placebo groups were headache, nausea, insomnia, anxiety, and 
dizziness. Serious AEs (ulcerative colitis, migraine, worsening of Axis II and 
mood disorder, and duodenal ulcer) were reported in 4 (1.5%) patients receiving 
armodafinil and were considered by the investigator not or unlikely to be drug 
related.
CONCLUSIONS: In this selected population of patients with OSA/HS and residual ES 
despite effective treatment with nCPAP, armodafinil QD used as an adjunct to 
nCPAP treatment was associated with improved wakefulness and overall clinical 
condition. Clinical benefit was shown at the first assessment and maintained for 
the 12-week duration of the study. Armodafinil was also associated with 
significantly reduced interference of ES with daily activities and global 
fatigue. Armodafinil was well tolerated, with no adverse effect on nighttime 
sleep or nCPAP use.