LONG-TERM EFFICACY AND SAFETY OF DONEPEZIL IN THE TREATMENT OF ALZHEIMERS-DISEASE - AN INTERIM ANALYSIS OF THE RESULTS OF A US MULTICENTER OPEN-LABEL EXTENSION STUDY

The long-term efficacy and safety of donepezil (up to 10 mg/day) was e valuated in a multicentre, non-randomised, open-label extension study of 133 patients with mild to moderate Alzheimer's disease (AD) who had completed a previous 14-week double-blind, placebo-controlled trial o f donepezil. Assessments were conducted at three-weekly intervals for 12 weeks, then 12-weekly for up to 192 weeks. Efficacy, assessed by th e Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) a nd Clinical Dementia Rating-Sum of the Boxes (CDR-SB), was examined in comparison with published data of untreated AD patients. Safety was m onitored by physical examinations, laboratory tests and vital sign mea surements. Results of this interim analysis (at 98 weeks) show that do nepezil produced improvements in cognition which remained superior to baseline for 38 weeks. CDR-SB likewise showed improvement, with scores maintained near baseline values for 26 weeks. Scores for both instrum ents then increased as expected in a progressive disease. However, the slope of score progression was less than has been historically report ed for untreated patients. While the lack of a concurrent placebo grou p does not allow conclusions about the ability of donepezil to attenua te disease progression, the data, nonetheless, demonstrate that there is no loss of treatment benefit over 98 weeks. Donepezil was well tole rated, with no evidence of hepatotoxicity. (C) 1998 Elsevier Science B .V./ECNP.