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| Sponsor: | Tel-Aviv Sourasky Medical Center |
|---|---|
| Collaborator: |
Israeli Ministry of Defense |
| Information provided by: | Tel-Aviv Sourasky Medical Center |
| ClinicalTrials.gov Identifier: | NCT00624663 |
Purpose
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
| Condition | Intervention |
|---|---|
|
Rivastigmine Toxicity |
Drug: Rivastigmine |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| 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 |
| Estimated Enrollment: | 16 |
| Study Start Date: | April 2008 |
| Estimated Study Completion Date: | September 2008 |
| Estimated Primary Completion Date: | June 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: 1
1 x 1.5 mg Exelon® Capsule (Novartis) + 1 x Placebo Capsule
|
Drug: Rivastigmine
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 Name: Exelon® Capsules (Novartis)
|
|
Active Comparator: 2
2 x 1.5 mg Exelon® Capsules (Novartis)
|
Drug: Rivastigmine
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 Name: Exelon® Capsules (Novartis)
|
|
Placebo Comparator: 3
2 x Placebo Capsules
|
Drug: Rivastigmine
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 Name: Exelon® Capsules (Novartis)
|
Eligibility| Ages Eligible for Study: | 18 Years to 40 Years |
| Genders Eligible for Study: | Male |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
• Known hypersensitivity to the drug, components or other carbamates.
Contacts and Locations| Contact: JACOB ATSMON, MD | 972-3-6974845 | qc@tasmc.health.gov.il |
| Israel | |
| Tel Aviv Sourasky Medical Center | |
| Tel Aviv, Israel | |
| Tasmc Clinical Research Center | |
| Tel-Aviv, Israel, 64239 | |
| Principal Investigator: | JACOB ATSMON, MD | TASMC CLINICAL RESEARCH CENTER |
More Information
| Responsible Party: | Jacob Atsmon, Tel-Aviv Sourasky Medical Center |
| ClinicalTrials.gov Identifier: | NCT00624663 History of Changes |
| Other Study ID Numbers: | TASMC-07-JA-234-CTIL, TRC 032/10058 |
| Study First Received: | October 30, 2007 |
| Last Updated: | February 15, 2008 |
| Health Authority: | Israel: Ministry of Health |
|
Rivastigmine, Repeated administration, Healthy Volunteers, organophosphate poisoning, protection, pharmacokinetics, behavioral effects |
|
Lactitol Rivastigmine Cathartics Gastrointestinal Agents Therapeutic Uses Pharmacologic Actions Cholinesterase Inhibitors Enzyme Inhibitors |
Molecular Mechanisms of Pharmacological Action Cholinergic Agents Neurotransmitter Agents Physiological Effects of Drugs Neuroprotective Agents Protective Agents Central Nervous System Agents |