A Double-Blind, Placebo-controlled Crossover Study of Repeat Rivastigmine Administration in Healthy Male Volunteers

Plain-language summary

Rivastigmine is a carbamate, approved by the FDA for the treatment of mild to moderate dementia associated with Alzheimer's and Parkinson's diseases. Studies conducted in the Israel Institute of Biological Research (IIBR) have yielded encouraging results in utilizing rivastigmine pre-treatment as an alternative to pyridostigmine in partially protecting against organophosphate poisoning, particularly protecting the central nervous system. The target population for this indication may consist of otherwise healthy people (e.g. soldiers). Although the treatment regimen has not been established yet it is assumed, based on animal experiments, that rivastigmine is likely to be administered in repeated doses. In this setting, further evaluation of the drug's effects and pharmacokinetics in young healthy subjects is warranted. The objectives of this study are: 1) To assess the safety and tolerability of repeated rivastigmine administration (1.5 mg and 3 mg) in young healthy male volunteers; 2) To determine the pharmacokinetic profile of rivastigmine (1.5 mg and 3 mg) following a single and multiple dose administrations; 3) To assess the extent of blood ChE inhibition following a single and multiple administrations of rivastigmine and 4) To correlate physiological and behavioral effects with blood rivastigmine concentrations and blood ChE inhibition in these subjects. This double-blind, placebo-controlled study will be divided in 3 identical periods, preceded with a two-day initial training in performing cognitive performance tests. Each period will consist of in-house confinement for 5 days in which rivastigmine will be administered 5 times at an interval of 12 hours. During each period, each subject will receive either rivastigmine 1.5 mg X 5, or either rivastigmine 3.0 mg X 5 or placebo X 5. The treatment in each period will be randomly assigned in a crossover manner. Rivastigmine pharmacokinetics will and acetylcholinesterase inhibition will be assessed after the first and the last dose of each period and will be correlated with physiological and cognitive parameters: performance tests, visual functions, peak airway flow, saliva production (sialometry) and vital signs. The emergence of adverse events will be monitored throughout the study

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