Investigation of Safety and Tolerability of ASP3652 Based on Clinical Studies of Cerebrospinal Fluid Transfer After Multiple Doses and Exposure After Single Doses at High Dose Levels.
Anandamide
Cerebrospinal fluid
Endocannabinoid
Fatty acid amide hydrolase
Healthy subjects
Pharmacodynamics
Pharmacokinetics
Journal
Advances in therapy
ISSN: 1865-8652
Titre abrégé: Adv Ther
Pays: United States
ID NLM: 8611864
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
09
06
2020
pubmed:
28
7
2020
medline:
2
3
2021
entrez:
28
7
2020
Statut:
ppublish
Résumé
The studies described here were conducted to investigate the central nervous system (CNS) transfer of ASP3652, a peripherally acting inhibitor of fatty acid amide hydrolase, after multiple doses at around the anticipated therapeutic dose and the safety, tolerability, and pharmacokinetics after single doses at corresponding supratherapeutic doses in healthy subjects. Study 1 was an open-label multiple dose study in which ASP3652 (300 mg bid) or matching placebo was administered in multiple doses to healthy subjects. Study 2 was a placebo-controlled, randomized 4 × 4 crossover study in which ASP3652 was given as three single ascending doses of ASP3652 (600-1800 mg) or matching placebo to healthy subjects. Levels of ASP3652 and endocannabinoids (eCBs) in plasma, cerebrospinal fluid (CSF) (study 1 only), and safety were evaluated. In study 1, ASP3652 was readily absorbed to reach C ASP3652 showed low CNS penetration at the anticipated therapeutic dose and was well tolerable without any CNS-related AEs at supratherapeutic doses, supporting that the drug can be safely tested at the anticipated therapeutic dose. ClinicalTrials.gov identifier, NCT02034734 for study 1, NCT01815684 for study 2.
Identifiants
pubmed: 32715381
doi: 10.1007/s12325-020-01451-6
pii: 10.1007/s12325-020-01451-6
doi:
Substances chimiques
Amidohydrolases
EC 3.5.-
fatty-acid amide hydrolase
EC 3.5.1.-
Banques de données
ClinicalTrials.gov
['NCT02034734', 'NCT01815684', 'NCT02034734']
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
3967-3984Références
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