This study evaluated daytime alertness and performance with
lisdexamfetamine dimesylate during acute sleep loss. In a randomized, double-blind study in healthy adult men (n = 135) undergoing 24-hour sleep loss, the alerting effects of single oral
lisdexamfetamine dimesylate doses (20, 50, or 70 mg) were compared with a placebo and an active control (
armodafinil 250 mg). Primary end point was mean unequivocal sleep latency on the 30-minute maintenance of wakefulness test taken every 2 hours from midnight to 8:00 A.M. Secondary end points included the Karolinska
sleepiness scale and psychomotor vigilance task. Safety assessments included treatment-emergent adverse events (TEAEs) and vital signs. Least squares mean (SE) maintenance of wakefulness test unequivocal sleep latency (in minutes) was longer with
lisdexamfetamine dimesylate 20, 50, and 70 mg, or
armodafinil 250 mg (23.3 [1.10], 27.9 [0.64], 29.3 [0.44], or 27.6 [0.63], respectively) versus placebo (15.3 [1.00]; P < 0.0001). Longer mean unequivocal sleep latency was seen with
lisdexamfetamine dimesylate 70 mg versus
armodafinil (P = 0.0351) and
armodafinil versus
lisdexamfetamine dimesylate 20 mg (P = 0.0014). On Karolinska
sleepiness scale,
lisdexamfetamine dimesylate 50 and 70 mg improved estimated
sleepiness versus placebo (P ≤ 0.0002) and
armodafinil (P ≤ 0.03). Active treatments improved psychomotor vigilance task performance versus placebo (P < 0.0001). The TEAEs were mild/moderate. No serious adverse events occurred. The most common TEAE was
headache with
lisdexamfetamine dimesylate and
armodafinil (7.4% each) versus placebo (3.7%). Small mean increases in vital signs were observed with
lisdexamfetamine dimesylate and
armodafinil. In sleep-deprived healthy men, alertness was greater with
lisdexamfetamine dimesylate and
armodafinil versus placebo on the primary end point. Studies are needed in clinical populations and using longer durations of administration.