Efficacy and safety of a novel, extended-release rivastigmine transdermal patch (TW-4752N) in patients with Alzheimer's disease: A 24-week randomized, double-blind trial with a 28-week open-label extension

Background Rivastigmine may offer greater efficacy and convenience of use with a novel formulation than previously reported. Objective To evaluate the efficacy and safety of a novel, twice-weekly rivastigmine patch (TW-4752N) (TW) in Alzheimer's disease (AD) patients with mild to moderate dementia. Methods This was a multicenter, phase III, double-blind study comparing TW and an existing rivastigmine transdermal patch (RT) with an open-label extension. The primary endpoint was the change in ADAS-Jcog total score at week 24 from baseline. Secondary endpoints included the ADAS-Jcog total score at weeks 8, 16, and 24. Results A total of 354 and 362 patients were available for efficacy and safety analysis, respectively. Changes in ADAS-Jcog total score at week 24 from baseline were similar between the two groups in the full analysis set with an intergroup difference of −0.84 ± 0.44 (95% CI, −1.695 to 0.016) and with the upper limit of the 95% CI being below the non-inferiority margin of 1.1, demonstrating the non-inferiority of TW. However, analysis of the per-protocol set demonstrated a significant intergroup difference in favor of TW likely suggesting a greater treatment effect with TW than with RT (p = 0.032). Adverse events (AEs) reported in ≥3% of patients were similar between the groups, with the only AE with an intergroup difference of ≥10% in incidence being application site pruritus (TW/RT, 27.6%/17.1%). Conclusions TW represents a viable alternative option of interest to patients with AD, providing comparable or potentially greater efficacy than RT and comparable safety, as well as greater convenience of use.