Safety and pharmacokinetics of the orally available antiprionic compound PRI-002: A single and multiple ascending dose phase I study.
Alzheimer´s disease (AD)
MAD
PRI‐002
SAD
anti‐Aβ‐prionic
first‐in‐human (FIH)
multiple ascending dose
pharmacokinetics
phase I
safety
single ascending dose
Journal
Alzheimer's & dementia (New York, N. Y.)
ISSN: 2352-8737
Titre abrégé: Alzheimers Dement (N Y)
Pays: United States
ID NLM: 101650118
Informations de publication
Date de publication:
2020
2020
Historique:
received:
05
11
2019
revised:
07
01
2020
accepted:
13
01
2020
entrez:
27
3
2020
pubmed:
27
3
2020
medline:
27
3
2020
Statut:
epublish
Résumé
PRI-002 is an orally available anti-amyloid beta (Aβ) prionic compound developed for direct disassembly of toxic Aβ oligomers relevant to Alzheimer's disease. Two placebo-controlled clinical phase I trials with oral dosing of PRI-002 were conducted in healthy young subjects: A single ascending dose trial (4, 12, 36, 108, or 320 mg PRI-002 or placebo) in 40 participants followed by a multiple ascending dose study with daily 160 mg PRI-002 for 14 days or 320 mg for 28 days in 24 participants. The main objectives were safety, tolerability, and evaluation of pharmacokinetic (PK) parameters. PRI-002 was safe and well tolerated after single and multiple oral administration up to the highest doses. PRI-002 was absorbed rapidly and drug exposure increased proportional to dose. During repeated daily administration, the drug accumulated by a factor of about three. Steady-state conditions were reached after 1 to 2 weeks. The safety and PK results encourage further clinical development of PRI-002.
Identifiants
pubmed: 32211506
doi: 10.1002/trc2.12001
pii: TRC212001
pmc: PMC7087413
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e12001Informations de copyright
© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.
Déclaration de conflit d'intérêts
The authors have no conflicts of interest to report.
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