Safety, Tolerability, and Efficacy of Armodafinil Therapy for Hypersomnia Associated with Dementia with Lewy Bodies (P04.192)

Abstract

Objective: To assess the safety, tolerability and efficacy of armodafinil therapy for hypersomnia associated with dementia with Lewy bodies (DLB). Background Recent analyses have demonstrated hypersomnia is often associated with DLB, but no data has been gathered on the safety, tolerability and efficacy of wake-promoting agents for hypersomnia in DLB. Design/Methods: We conducted an open-label pilot study using armodafinil 250 mg taken orally every morning in patients with hypersomnia associated with DLB. Subjects underwent assessment of cognition (Mini-Mental State Exam-MMSE), visual hallucinations (NPI-VH), apathy (NPI-A), daytime sleepiness (Epworth Sleepiness Scale-ESS), and quality of life (QOL) at baseline and after 1, 2, and 3 months of therapy. The Maintenance of Wakefulness Test (MWT) was also conducted at baseline and at 3 months, in which the mean initial sleep latencies (ISL) across 4 naps were analyzed. Safety and tolerability were assessed by clinical evaluations, laboratory studies and electrocardiogram (ECG). Results: Fifteen subjects (12 male, median age 74 years, range 67-84 years) have completed most or all the 3 month protocol thus far, with 1 discontinuing near completion due to worsening disease and 1 expiring from community-acquired pneumonia. Of the 13 subjects with baseline and 3 month MWTs, 11 subjects improved (median value 11 minutes, range 1-22 minutes). Improvement on the ESS occurred in 14 subjects (median 6 points, range 1-15). MMSE scores were relatively stable (+/- 4 points) compared to baseline except for a 6 point improvement in 1 subject. Scores improved on the NPI-VH in 6 and on the NPI-A in 10. QOL was rated as improved in 7 subjects and in 7 caregivers. No clinically significant side-effects, laboratory abnormalities, or ECG abnormalities occurred except for prolongation of the QTc interval in 1 subject. Conclusions: These pilot data suggest reasonable safety, tolerability and efficacy of armodafinil therapy in hypersomnolent DLB subjects. Supported by: Funded by Cephalon, Inc. Disclosure: Dr. Kuntz has received research support from Cephalon, Inc. Dr. Boeve has nothing to disclose. Dr. Drubach has received research support from Allon Therapeutics. Dr. Allen has nothing to disclose. Dr. Drubach has received research support from Allon Therapeutics.