Pharmacokinetics and Pharmacodynamics of the BACE1 Inhibitor Verubecestat (MK-8931) in Healthy Japanese Adults: A Randomized, Placebo-Controlled Study.
Clin Pharmacol Ther
; 105(5): 1234-1243, 2019 05.
Article
em En
| MEDLINE
| ID: mdl-30347431
ABSTRACT
ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) is required for the production of ß-amyloid (Aß) 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 Aß proteins Aß40, Aß42, and soluble ß 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tiadiazinas
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Peptídeos beta-Amiloides
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Ácido Aspártico Endopeptidases
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Óxidos S-Cíclicos
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Secretases da Proteína Precursora do Amiloide
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Doença de Alzheimer
Tipo de estudo:
Clinical_trials
/
Guideline
Limite:
Adult
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Female
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Humans
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Male
País/Região como assunto:
Asia
Idioma:
En
Revista:
Clin Pharmacol Ther
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos