Abstract
Background: Tarenflurbil is a Selective Ab42-Lowering Agent (SALA) that lowers brain levels of Ab42 in a mouse model of AD and chronic dosing in this model prevents defects in learning and memory. These data and the Phase-2 study indicating sustained benefit in activities of daily living, global function and cognition in mild AD patients, suggest the potential for tarenflurbil to have disease-modifying properties. Methods: This was a placebo-controlled, 1-year study evaluating tarenflurbil in 207 patients with mild-to-moderate AD. At randomization, 94% of subjects were on stable acetylcholinesterase inhibitor therapy. An exploratory post-hoc analysis was performed which compared time to adverse psychiatric events between treatment groups. Results: In subjects with mild AD (MMSE 20–26) was a significant delay in time to clinically significant adverse psychiatric events, 800 mg BID compared to placebo (p=0.011). Among 35% of the placebo group who had an event, the median time was approximately 106 days. In the 800 mg BID group, the median time to event was greater than 333 days with only 14% of this group having an event. The most common psychiatric events reported in the placebo group were agitation, aggression, confusional state and depression.