Effects of single doses of Avagacestat (BMS-708163) on cerebrospinal fluid Aβ levels in healthy young men.

Tong G, Castaneda L, Wang JS, Sverdlov O, Huang SP, Slemmon R, Gu H, Wong O, Li H, Berman RM, Smith C, Albright C, Dockens RC.
Journal   Clin Drug Investig.
Species  
Analytes Measured   Abeta 38 , Abeta 40 , Abeta 42
Matrix Tested   Cerebrospinal fluid (CSF)
Year   2012
Volume  
Page Numbers  
Application   Alzheimers
Abstract
BACKGROUND: The concentration of amyloid β (Aβ) peptides in cerebrospinal fluid (CSF) is a biomarker for Alzheimer's disease (AD) pathology, and has been used to evaluate the effectiveness of γ-secretase inhibition. Avagacestat is a selective γ-secretase inhibitor in development for the treatment of AD. The primary objective of this study was to assess the effects of single oral doses of avagacestat on the CSF Aβ concentrations in healthy male subjects. Secondary objectives included single-dose pharmacokinetics in CSF and plasma, safety and tolerability.

METHODS: This was a double-blind, placebo-controlled, randomized, single-dose study. Healthy male subjects were assigned to one of three sequential avagacestat dose panels (50, 200 and 400 mg) or placebo as single oral doses.

RESULTS: 34 subjects were enrolled. Administration of a single dose of 200 or 400 mg of avagacestat resulted in a marked decrease in CSF Aβ1-38, Aβ1-40 and Aβ1-42 concentrations vs placebo; with smaller decreases observed in the 50 mg dose group. Avagacestat was quickly absorbed into the systemic circulation, with a mean time to reach maximum plasma concentration (tmax) of approximately 1-2 h, and a CSF tmax of approximately 3 h. Adverse events were uncommon and occurred with similar frequency in the placebo and avagacestat groups.

CONCLUSION: Avagacestat was safe, well tolerated, and resulted in a notable decrease in CSF Aβ concentrations, suggestive of γ-secretase inhibition. The results warrant further clinical study in patients with AD.

View Publications

Related Products

R-PLEX Human Aβ42 (6E10) Antibody Set
Aβ42 (6E10) | Human
Singleplex
NEW
R-PLEX Human Aβ40 (6E10) Antibody Set
Aβ40 (6E10) | Human
Singleplex
NEW
Human (6E10) Aβ38 Ultra-Sensitive Kit
Aβ38 | Human
Singleplex
Human (6E10) Aβ40 Ultra-Sensitive Kit
Aβ40 | Human
Singleplex
Human (6E10) Aβ42 Ultra-Sensitive Kit
Aβ42 | Human
Singleplex
V-PLEX Human Aβ42 Kit
Aβ42 | Human
Singleplex
V-PLEX Aβ Peptide Panel 1 (4G8) Kit
Aβ38, Aβ40, Aβ42 | Human, Mouse, Rat
Multiplex
V-PLEX Aβ Peptide Panel 1 (6E10) Kit
Aβ38, Aβ40, Aβ42 | Human
Multiplex
V-PLEX Aβ40 Peptide (4G8) Kit
Aβ40 | Human, Mouse, Rat
Singleplex
V-PLEX Aβ40 Peptide (6E10) Kit
Aβ40 | Human
Singleplex
V-PLEX Aβ42 Peptide (4G8) Kit
Aβ42 | Human, Mouse, Rat
Singleplex
V-PLEX Plus Aβ Peptide Panel 1 (4G8) Kit
Aβ38, Aβ40, Aβ42 | Human, Mouse, Rat
Multiplex
V-PLEX Plus Aβ Peptide Panel 1 (6E10) Kit
Aβ38, Aβ40, Aβ42 | Human
Multiplex
V-PLEX Plus Aβ40 Peptide (4G8) Kit
Aβ40 | Human, Mouse, Rat
Singleplex
V-PLEX Plus Aβ40 Peptide (6E10) Kit
Aβ40 | Human
Singleplex
V-PLEX Plus Aβ42 Peptide (4G8) Kit
Aβ42 | Human, Mouse, Rat
Singleplex
V-PLEX Plus Human Aβ42 Kit
Aβ42 | Human
Singleplex
Neurodegeneration Control Pack 1
Aβ38, Aβ40, Aβ42, Tau (total) | Human, Mouse, Rat
V-PLEX Aβ38 Peptide (4G8) Kit
Aβ38 | Human, Mouse, Rat
Singleplex
V-PLEX Aβ38 Peptide (6E10) Kit
Aβ38 | Human
Singleplex
V-PLEX Plus Aβ38 Peptide (4G8) Kit
Aβ38 | Human, Mouse, Rat
Singleplex
V-PLEX Plus Aβ38 Peptide (6E10) Kit
Aβ38 | Human
Singleplex
Browse Our Products

By Analytes
By Applications
Search
Customer Service/Orders


Scientific/Technical Support


Instrument Support


Company Headquarters