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Abstract: Poster Presentations |

COMPARISON BETWEEN ARMODAFINIL AND MODAFINIL USING CONCENTRATION-EFFECT RELATIONSHIP IN PATIENTS WITH EXCESSIVE SLEEPINESS ASSOCIATED WITH TREATED OBSTRUCTIVE SLEEP APNEA: A PHARMACOKINETIC/PHARMACODYNAMIC MODEL FREE TO VIEW

Mona Darwish, PhD*; Lauren S. Young, BSc; Mary Kirby, MS; Farkad Ezzet, PhD
Author and Funding Information

Clinical Pharmacology Department, Cephalon, Inc., Frazer, PA


Chest


Chest. 2009;136(4_MeetingAbstracts):70S-b-71S. doi:10.1378/chest.136.4_MeetingAbstracts.70S-b
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Abstract

PURPOSE:  To quantitatively compare the efficacy of armodafinil with that of modafinil on a milligram-to-milligram basis in patients with residual excessive sleepiness (ES) associated with obstructive sleep apnea (OSA) treated with continuous positive airway pressure (CPAP).

METHODS:  A nonlinear, mixed-effect pharmacokinetic/pharmacodynamic (PK/PD) model determined the relationship between concentration and effect of armodafinil and modafinil in patients with ES associated with treated OSA. The concentrations were estimated from a population PK model established using pooled PK data of armodafinil and modafinil in healthy volunteers and in patients. The PD was pooled Maintenance of Wakefulness Test (MWT) data from randomized, double-blind, placebo-controlled studies of armodafinil or modafinil in patients with ES associated with treated OSA.

RESULTS:  Based upon data from over 900 patients, there was an agreement between mean (observed) response and model prediction (fit) for all treatments, suggesting appropriateness of the model, with no bias. After accounting for study differences, the PK/PD model determined that the estimated EC50 (the concentration producing 50% of maximal drug effect) of both drugs was 8.4 ng/mL and the EC30 was 3.6 ng/mL. The estimated plasma concentration-over-time profile suggests that once-daily armodafinil 200 mg would result in plasma drug concentrations above the EC30 for up to 12 hours while modafinil 200 mg would result in concentrations above EC30 for < 6 hours. It was predicted that, compared with placebo, armodafinil 200 mg would improve average sleep latency by > 1.5 minutes through 3 PM on the individual MWT sessions compared with < 1.5 minutes for modafinil 200 mg.

CONCLUSION:  A pharmacokinetic/pharmacodynamic model based on MWT in patients with residual ES associated with treated OSA predicted that the improvement in wakefulness would be consistently higher for armodafinil compared with modafinil on a milligram-to-milligram basis.

CLINICAL IMPLICATIONS:  These results suggest that armodafinil 200 mg may provide greater improvements in wakefulness throughout the day, especially at later times, compared with modafinil 200 mg in patients with residual ES associated with CPAP-treated OSA.

DISCLOSURE:  Mona Darwish, No Financial Disclosure Information; No Product/Research Disclosure Information

Tuesday, November 3, 2009

12:45 PM - 2:00 PM


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