Profiling the dynamics of CSF and plasma Aβ reduction after treatment with JNJ-54861911, a potent oral BACE inhibitor.

ABSTRACT:

Objectives

Safety, tolerability, pharmacokinetics, and pharmacodynamics of a novel β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor, JNJ-54861911, were assessed after single and multiple dosing in healthy participants.

Methods

Two randomized, placebo-controlled, double-blind studies were performed using single and multiple ascending JNJ-54861911 doses (up to 14 days) in young and elderly healthy participants. Regular blood samples and frequent CSF samples, up to 36 hours after last dose, were collected to assess the pharmacokinetic and pharmacodynamic (Aβ, sAPPα,β,total levels) profiles of JNJ-54861911.

Results

JNJ-54861911 was well-tolerated, adverse events were uncommon and unrelated to JNJ-54861911. JNJ-54861911 showed dose-proportional CSF and

SUBMITTER: Timmers M 

PROVIDER: S-EPMC5651349 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature