PURPOSE: Notwithstanding appropriate continuous positive airway pressure (CPAP) usage of ≥ 6 hours per night, approximately 52% of patients with obstructive sleep apnea (OSA) continue to experience residual excessive sleepiness (ES). Armodafinil is the longer acting R-enantiomer of racemic modafinil and represents a next generation, non-amphetamine, wakefulness-promoting agent. It was found effective in patients with OSA who have ES despite regular CPAP use. The racemate may require split or higher dosing to sustain clinical benefit across the day. The R-enantiomer lasts 3 times as long as the S-enantiomer and thereby produces higher sustained plasma concentrations later in the day when compared to modafinil. The purpose of these analyses was to test the ability of armodafinil to improve and sustain wakefulness throughout the day when administered once daily.
METHODS: Post hoc analyses of data from a 12-week, multicenter, double-blind, randomized, placebo-controlled study of regular CPAP users with OSA experiencing residual ES (n=395) who received armodafinil (150 or 250 mg) or placebo once daily. Efficacy outcome was the mean sleep latency of the first 5 of 6 20-min Maintenance of Wakefulness Test subtests administered every two hours beginning at 0900.
RESULTS: Armodafinil improved mean sleep latency (0900–1700) with treatment differences of 3.1, 3.5, and 3.3 mins in the 150-mg, 250-mg, and armodafinil combined groups, respectively, compared with placebo at final visit versus baseline (all, nominal P<0.003). At each individual subtest, the armodafinil groups showed greater improvement versus the placebo group. Armodafinil was generally well tolerated.
CONCLUSION: Once-daily adjunctive armodafinil improved the ability to sustain wakefulness throughout the day in CPAP-treated patients with ES associated with OSA.
CLINICAL IMPLICATIONS: Patients with residual ES associated with OSA who regularly use CPAP benefit from sustained wakefulness throughout the day following once daily armodafinil treatment.
DISCLOSURE: Max Hirshkowitz, Grant monies (from industry related sources) Hirshkowitz: Merck, Evotec, Cephalon, Sanofi-Aventis, Sepracor, Takeda, Organon, Vanda. Lankford: Actelion, Arena, Cephalon, Evotec, GlaxoSmithKline, Lilly, Merck, Neurim, Neurocrine, Neurogen, Organon, Pfizer, Respironics, Sanofi-Aventis, Somaxon, Takeda, Transcept, Vanda. Roth: Sanofi-Aventis, Cephalon, GlaxoSmithKline, Neurocrine, Pfizer, Schering-Plough, Sepracore, Somaxon, Syrex, Takeda, TransOral, Wyeth, Xenoport.; Shareholder Steven C.K. Chang; Gregory A. Rippon; Employee Chang: Employee and receiving stock or stock options from Cephalon, Inc. Rippon: Employee and has equity interest.; Consultant fee, speaker bureau, advisory committee, etc. Hirshkowitz: Cephalon, Takeda, Sanofi-Aventis. Lankford: Actelion, Cephalon, Concert, GlaxoSmithKline, Jazz, Neurocrine, Neurocrine, Neurogen, Ovation, Pfizer, Somaxon, Transcept. Roth: Abbott, Actelion, Arena, BTG, Cephalon, Evotec, Intec, Intra-Cellular, Jazz, Merck, Neurim, Neurocrine, neurogen, Organon, Proctor and Gramble, Pfizer, Sanofi-Aventis, Schering-Plough, Sepracor, Shire, Somaxon, Takeda, TransOral, Vanda.; No Product/Research Disclosure Information