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.


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.


METHODS
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.


CONCLUSIONS
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.
Dinges
David F
DF
University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6021, USA. dinges@mail.med.upenn.edu
Arora
Sanjay
S
Darwish
Mona
M
Niebler
Gwendolyn E
GE
D000293:Adolescent; D000328:Adult; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D000077408:Modafinil; D010919:Placebos; D012892:Sleep Deprivation / Q000188:drug therapy*; D013237:Stereoisomerism; D014851:Wakefulness / Q000187:drug effects*
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D010919:Placebos; D000077408:Modafinil