A phase 3, double-blind, randomized, placebo-controlled study of armodafinil for excessive sleepiness associated with jet lag disorder

Abstract

Objective: To assess the effect of armodafinil, the longer-lasting isomer of modafinil, on jet lag disorder.

Participants and methods: This double-blind, randomized, parallel-group, multicenter study was conducted between September 18, 2008, and February 9, 2009. Adults with a history of jet lag symptoms on previous flights through multiple time zones flew from the United States to France (a 6-hour time zone change) for a 3-day laboratory-based study period. Participants received armodafinil (50 or 150 mg/d) or placebo each morning. Wakefulness was assessed by the coprimary outcomes, mean sleep latency on the Multiple Sleep Latency Test (MSLT) (average of all MSLT sessions across days 1 and 2) and Patient Global Impression of Severity in relation to jet lag symptoms (averaged across days 1 and 2).

Results: A total of 427 participants received armodafinil at 50 mg/d (n=142), armodafinil at 150 mg/d (n=143), or placebo (n=142). Armodafinil at 150 mg/d provided a significant benefit in sleep latency on the MSLT (days 1-2: mean, 11.7 minutes vs 4.8 minutes for placebo; P<.001) and participants' perception of their overall condition in relation to jet lag symptoms (Patient Global Impression of Severity, days 1-2: mean, 1.6 vs 1.9 for placebo; P<.05). The most frequently reported adverse events for armodafinil at 150 mg/d were headache (27%), nausea (13%), diarrhea (5%), circadian rhythm sleep disorder (5%), and palpitations (5%).

Conclusion: Armodafinil increased wakefulness after eastward travel through 6 time zones.

Trial registration: clinicaltrials.gov identifier: NCT00758498.

Figures

FIGURE 1.

Study design.

FIGURE 2.

Participant disposition. *One participant did not have any postbaseline efficacy assessments performed.

FIGURE 3.

Mean (SD) scores on the Multiple Sleep Latency Test (MSLT), Patient Global Impression of Severity (PGI-S), and Karolinska Sleepiness Scale (KSS) across days 1 and 2. * P<.001, analysis of covariance. † P=.04, Cochran-Mantel-Haenszel test. ‡ Average of the 4 KSS assessments performed before the MSLT (daytime assessments).