title: Maintenance of wakefulness with lisdexamfetamine dimesylate, compared with placebo and armodafinil in healthy adult males undergoing acute sleep loss.
abstract: 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.
authors.affiliation: From the *Shire Development LLC, Wayne, PA; †Clinilabs, Inc, New York, NY; and ‡Henry Ford Hospital Sleep Center, Detroit, MI.
authors.forename: Maria
authors.initials: M
authors.lastname: Gasior
authors.forename: Jon
authors.initials: J
authors.lastname: Freeman
authors.forename: Gary
authors.initials: G
authors.lastname: Zammit
authors.forename: Patricia
authors.initials: P
authors.lastname: Donnelly
authors.forename: Joseph
authors.initials: J
authors.lastname: Gao
authors.forename: Maria Celeste
authors.initials: MC
authors.lastname: Ferreira-Cornwell
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001559:Benzhydryl Compounds / Q000008:administration & dosage*; D003913:Dextroamphetamine / Q000008:administration & dosage*; D004311:Double-Blind Method; D006304:Health Status; D006801:Humans; D000069478:Lisdexamfetamine Dimesylate; D008297:Male; D000077408:Modafinil; D012892:Sleep Deprivation / Q000175:diagnosis / Q000188:drug therapy*; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology; D064690:Wakefulness-Promoting Agents / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D064690:Wakefulness-Promoting Agents; D000077408:Modafinil; D000069478:Lisdexamfetamine Dimesylate; D003913:Dextroamphetamine