P4‐354: HEMORRHAGIC BULLOUS LESION AFTER RIVASTIGMINE PATCH TREATMENT

randomized, double-blind, placebo-controlled, multinational study targeted enrollment of 420 subjects with mild-to-moderate AD (MiniMental Status Examination [MMSE] score of 12-24, inclusive). Subjects receiving stable doses of donepezil or rivastigmine were randomized to ABT-126 (25mg or 75mg QD) or placebo for 24 weeks. The primary efficacy endpoint was the change from baseline to Week 24 in the 11-item Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog) total score. It was analyzed by mixed-effects model for repeated measures using factors of treatment, site, visit and treatment-by-visit interaction, with baseline score and baseline-by-visit interaction as covariates. All P values shown are one-sided. A prespecified subgroup analysis examined the effects of ABT-126 by baseline disease severity (MMSE 12-19 or 20-24). Adverse events (AEs) were monitored, and sparse pharmacokinetic samples were collected.Results: The study randomized 434 patients with mean (SD) age of 75.1 (7.7) years and mean (SD) baseline MMSE of 18.9 (4.4) (no significant difference across treatment groups). Fifty-seven (13.1%) subjects prematurely discontinued (comparable across treatment groups). Neither dose of ABT-126 separated significantly from placebo on the 11-item ADAS-Cog (LS mean [SE] difference from placebo: 25 mg: -0.80 [0.59], P 1⁄40.087; 75 mg: -0.13 [0.59], P 1⁄40.416). In subjects with mild AD (MMSE 20-24), the treatment difference between 25 mg ABT-126 and placebo on the ADASCog was more pronounced (1.44 point improvement over placebo at Week 24, P 1⁄40.022). ABT-126 plasma levels were consistent with predictions. Among treatment groups, AE and serious AE rates (SAE) were comparable (placebo, 25 mg, and 75 mg): AE (68%, 64%, 70%), SAE (8.9%, 6.3%, 6.9%). Common AEs are shown in Table 1. Conclusions: ABT-126 did not improve performance on the AD AS-Cog in subjects with mild-to-moderate AD, but in subjects with mild AD the 25 mg dose showed a small, statistically significant improvement versus placebo. ABT-126 had an adequate safety profile in these mild-to-moderate AD patients.