Pharmacokinetics and Pharmacodynamics of the BACE 1 Inhibitor Verubecestat ( MK ‐8931) in Healthy Japanese Adults: A Randomized, Placebo‐Controlled Study
| Autor: | Julie A. Stone, Mark S. Forman, Marissa F. Dockendorf, John Palcza, Lei Ma, Michael Tanen, Marianne van Vugt, Matthew D. Troyer, Huub Jan Kleijn, Kazuko Masuo, Peter Hodsman, Jack Tseng, K Chris Min |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Placebo-controlled study Pharmacology 030226 pharmacology & pharmacy Drug Administration Schedule law.invention Amyloid beta-Protein Precursor 03 medical and health sciences 0302 clinical medicine Cerebrospinal fluid Japan Randomized controlled trial Pharmacokinetics Alzheimer Disease law Amyloid precursor protein Aspartic Acid Endopeptidases Humans Medicine Pharmacology (medical) Amyloid beta-Peptides Dose-Response Relationship Drug Thiadiazines biology business.industry Healthy Volunteers Cyclic S-Oxides Dose–response relationship 030220 oncology & carcinogenesis Pharmacodynamics biology.protein Verubecestat Female Amyloid Precursor Protein Secretases Drug Monitoring business |
| Zdroj: | Clinical Pharmacology & Therapeutics. 105:1234-1243 |
| ISSN: | 1532-6535 0009-9236 |
| DOI: | 10.1002/cpt.1258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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