A Double-Blind, Placebo-controlled Crossover Study of Repeat Rivastigmine Administration in Healthy Male Volunteers
Condition: Rivastigmine Toxicity
Study type: Interventional

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
    


Intervention name(s): Rivastigmine
Intervention type(s): Drug
Intervention description(s): Administration 1 (A): 1 x 1.5 mg Exelon® Capsule (Novartis) + 1 x Placebo Capsule Administration 2 (B): 2 x 1.5 mg Exelon® Capsules (Novartis) Administration 3 (C): 2 x Placebo Capsules
Other intervention name(s): Exelon® Capsules (Novartis)
Intervention MeSH terms: Rivastigmine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Rivastigmine, Repeated administration, Healthy Volunteers, organophosphate poisoning, protection, pharmacokinetics, behavioral effects