Pharmacodynamic effects on alertness of single doses of armodafinil in healthy subjects during a nocturnal period of acute sleep loss.

Objective: To assess the pharmacodynamics of armodafinil compared with modafinil and placebo on measures of alertness in healthy volunteers undergoing sleep loss.

Research Design And Methods: In a double-blind, active- and placebo-controlled, parallel-group study, 107 healthy male volunteers (aged 18-40 years) were randomized to receive a single oral dose of armodafinil (100, 150, 200, or 300 mg), modafinil (200 mg), or placebo administered at 19:25 h.

Main Outcome Measures: The primary outcome was the Maintenance of Wakefulness Test (MWT), administered every 2 hours from 22:00-08:00 h. Secondary outcomes included the Psychomotor Vigilance Task (PVT) and the Karolinska Sleepiness Scale. Blood samples for pharmacokinetic analysis were collected hourly. Adverse events were evaluated throughout the 2-day laboratory stay and by telephone on day 9.

Results: All four doses of armodafinil, and the dose of 200 mg modafinil, improved wakefulness as measured by increased MWT latencies (treatment effect, p < 0.0001) and reduced PVT lapses of attention (treatment effect, p < 0.0001). The magnitude and duration of these effects at the later time points appeared to be dose and concentration dependent. Armodafinil at 200 mg resulted in comparable C(max), a later t(max), and higher plasma concentrations 6-14 hours post-drug administration than with 200 mg modafinil. Following armodafinil, longer MWT latencies and fewer PVT lapses 6 to approximately 14 hours post-drug administration were observed compared with modafinil. Armodafinil doses were well tolerated, with the most common adverse events including abdominal pain, nausea, and headache. There were reports of tachycardia/palpitations. Decreased mean sleep efficiency and increased mean blood pressure were also observed.

Conclusion: Armodafinil improved alertness at all doses studied. Relative to modafinil 200 mg, armodafinil 200 mg showed a comparable peak plasma concentration with higher concentrations 6-14 hours post-drug, and improved wakefulness and sustained attention for a longer time post-dose. Both drugs were well tolerated; however, further research on the efficacy, safety, and tolerability of armodafinil in patients with disorders of excessive sleepiness (ES) is required.