β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is required for the 
production of β-amyloid (Aβ) peptides and is considered a potential treatment 
target for Alzheimer's disease (AD). To support Japan's participation in the 
global clinical development program, we characterized the safety, 
pharmacokinetics (PKs), and pharmacodynamics of the BACE1 inhibitor verubecestat 
(MK-8931) in 24 healthy Japanese adults in a two-part, single-center, 
randomized, placebo-controlled phase I trial (protocol MK-8931-007) and compared 
the results with historical data from non-Japanese subjects. Both single (20, 
100, and 450 mg) and multiple (80 and 150 mg once daily for 14 days) doses of 
verubecestat were well tolerated. Verubecestat's PK profile was similar in 
Japanese and non-Japanese subjects. Verubecestat also reduced mean cerebrospinal 
fluid concentrations of the Aβ proteins Aβ40, Aβ42, and soluble β fragment of 
amyloid precursor protein; the level of reduction was comparable between 
Japanese and non-Japanese subjects. These results support the continued global 
development of verubecestat as a potential disease-modifying agent for Japanese 
and non-Japanese subjects who are at risk for developing AD.