THE SYNTHESIS AND PRECLINICAL STUDIES OF NEW TREATMENTS FOR NEURODEGENERATIVE DISEASE, DIABETES MELLITUS, CONGESTIVE HEART FAILURE, ONCOLOGIC AND IMMUNOLOGIC DISEASES

Sri International, Menlo Park CA

Investigators

Abstract

(-)-Bisnorcymserine (BNC) is a new Alzheimer?s disease (AD) experimental drug developed within the Intramural Research Program (IRP) of NIA for late stage disease - for which effective new drugs represent a current medical need. The preclinical safety profile of BNC has been determined from: single oral and intravenous toxicity studies in mice, rats and dogs; repeated dose oral toxicity studies of up to 14 days in rats and dogs; and genotoxicity studies. The results of these studies support the safety of BNC in humans. Additionally, BNC demonstrated valuable actions across a number of preclinical studies - supportive of its potential value in humans with AD. BNC is being administered in a classical single dose escalation first in human phase 1 study undertaken within IRP/NIA. Specifically, in accord with an approved clinical protocol, and with IND No. 109,540 (Bisnorcymserine (BNC) for the Treatment of Alzheimer?s Disease), BNC (in the form of its tartrate salt) is being administered orally to healthy volunteers aged 55 years and older using a double-blind placebo-controlled design. The initial dose was 20 mg. The aim of the present contract was to evaluate BNC time-dependent drug levels in plasma samples obtained from the volunteers administered either BNC or a placebo in the initial round of the BNC phase 1 clinical trial to evaluate the pharmacokinetics of this new experimental AD drug.