Rivastigmine Toxicity Clinical Trial
Official title:
A Double-Blind, Placebo-controlled Crossover Study to Assess the Pharmacokinetic Profile and the Physiological and Behavioral Effects of Repeat Rivastigmine (Exelon®) Administration in Young Healthy Male Volunteers
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
n/a
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment