Rivastigmine ToxicityRIVA-1NCT00624663
A Double-Blind, Placebo-controlled Crossover Study of Repeat Rivastigmine Administration in Healthy Male Volunteers
A study testing Rivastigmine in people with Rivastigmine Toxicity, run by Tel-Aviv Sourasky Medical Center at 2 sites in Israel.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Rivastigmine Toxicity
- What is being tested?
- Rivastigmine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 2 sitesIsrael
- Study dates
- Jan 2009to Apr 2009
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy Caucasian males between 18 and 40 years (inclusive) of age.
- No known history of significant neurological, renal, cardiovascular, respiratory (asthma), endocrinological, gastrointestinal, hematopoietic disease, neoplasm or any other clinically significant medical disorder, which in the investigator's judgment contraindicate administration of the study medications.
- Subjects within BMI 18-29 (inclusive) calculated as Weight (Kg)/Height (m)2.
- Non-smoking (by declaration) for a period of at least 6 months.
- No history of drug or alcohol abuse.
- Subjects with negative urinary drugs of abuse screen (Appendix 2) determined within 21 days of the start of the study.
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- Negative HIV, Hepatitis B or Hepatitis C serology tests within 21 days of the first study session.
- Subjects must be able to adhere to the visit schedule and protocol requirements and be available to complete the study.
- Subjects must be fluent in Hebrew
- Subjects must satisfy a medical examiner about their fitness to participate in the study.
- Subjects must provide written informed consent to participate in the study.
Who cannot join
- • Known hypersensitivity to the drug, components or other carbamates.
- History of or currently active asthma or chronic obstructive pulmonary disease.
- History of or currently active cardiac arrhythmias such as bradycardia and sick sinus syndrome
- History of urinary tract obstruction.
- History of or currently active GI diseases such as peptic ulcer, GERD, bleeding or history of any GI surgery other than appendectomy or herniotomy, or with any gastrointestinal disorder likely to influence drug absorption, or with any history of anorexia, frequent nausea or emesis, regardless of etiology.
- Significant abnormalities in screening physical exam
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- Significant abnormalities in clinical laboratory parameters (hematology, biochemistry, serology, urinalysis). Parameters to be measured are those shown in Appendix 2.
- Significant abnormalities in ECG within 21 days of the start of the study.
- Subjects with significant allergic response to other drugs.
- Adherence (for whatever reason) to an abnormal diet during the 4 weeks prior to the study, or subjects with recent significant change in body weight.
- Subjects who have taken anticholinergic or other drugs known to affect gastrointestinal motility within 7 days prior to the first dosing.
- Use of any prescription or over-the-counter (OTC) medications, including vitamins and herbal or dietary supplements within 7 days prior to the first study dosing or during the study. Paracetamol for symptomatic relief of pain is allowed until 24 hours prior to the trial (see section 10.1).
- Subjects who donated blood in the three months preceding the first study dosing or intend to make blood donation during the study, or within the three months following the study completion.
- Subjects who received blood or plasma derivatives in the 3 months preceding the first study dosing.
- Participation in another clinical trial with drugs within 3 months prior first study dosing.
- Subjects with an inability to communicate well with the investigators and CRC staff (i.e., language problem, poor mental development or impaired cerebral performance).
- Subjects that have difficulty fasting or consuming the standard meals that will be provided.
- Subjects with any acute medical situation (e.g. acute infection) within 48 hours of study start, which is considered of significance by the Principal Investigator.
- Subjects who are non-cooperative or unwilling to sign a consent form.
Trial locations and contacts
2 sites in 1 country.
Israel2 sites
Tasmc Clinical Research Center
Tel Aviv, 64239
Tel Aviv Sourasky Medical Center
Tel Aviv
About this study
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.
Read more
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
- Conditions
- Rivastigmine Toxicity
- Being tested
- Rivastigmine
- Keywords
- Rivastigmine, Repeated administration, Healthy Volunteers, organophosphate poisoning, protection, pharmacokinetics, behavioral effects
- Medical subject headings
- Organophosphate Poisoning
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RivastigmineDrug
Also called Exelon® Capsules (Novartis)
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
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | (1 x 1.5 mg Exelon® Capsule (Novartis) + 1 x Placebo Capsule) X 2 per day, total of 5 intakes Receives: Drug: Rivastigmine |
| 2 | Active comparator | (2 x 1.5 mg Exelon® Capsules) X 2 per day, total of 5 intakes Receives: Drug: Rivastigmine |
| 3 | Placebo comparator | (2 x Placebo Capsules) X 2 per days, total of 5 intakes Receives: Drug: Rivastigmine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Physiological effects,Objective and subjective symptoms, Cognitive Performance tests
Measured: 5 weeks
Secondary outcomes (1)
4. Pharmacokinetic parameters (Cmax, Tmax, AUCT, AUCI ) determined from plasma rivastigmine concentrations,Blood cholinesterase inhibition
Measured: 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2008 (estimated)
- Study startJan 2009
- Primary completionApr 2009
- Study completionApr 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rivastigmine ToxicityStudies of the same condition, open and under way.
- More trials run by Tel-Aviv Sourasky Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tel-Aviv Sourasky Medical Center
- Sponsor type
- Other government
- Collaborators
- Medical Corps, Israel Defense Force
- Investigators
- JACOB ATSMON, MD, Principal investigator, TASMC CLINICAL RESEARCH CENTER
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00624663
- Sponsor's protocol ID
- TASMC-07-JA-234-CTIL
- Other IDs
- TRC 032/10058
- Acronym
- RIVA-1
- Status last verified
- Feb 2008
- First submitted
- 30 Oct 2007
- Last updated
- 27 Mar 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00624663
- Acronym / sponsor ID
- RIVA-1 / TASMC-07-JA-234-CTIL
- Conditions
- Rivastigmine Toxicity
- Keywords
- Rivastigmine, Repeated administration, Healthy Volunteers, organophosphate poisoning, protection, pharmacokinetics, behavioral effects
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Tel-Aviv Sourasky Medical CenterOther government
- Collaborators
- Medical Corps, Israel Defense Force
- Study start
- Jan 2009
- Primary completion
- Apr 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 27 Feb 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Rivastigmine(1 x 1.5 mg Exelon® Capsule (Novartis) + 1 x Placebo Capsule) X 2 per day, total of 5 intakes |
| 2 | Active comparator | Drug: Rivastigmine(2 x 1.5 mg Exelon® Capsules) X 2 per day, total of 5 intakes |
| 3 | Placebo comparator | Drug: Rivastigmine(2 x Placebo Capsules) X 2 per days, total of 5 intakes |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Healthy Caucasian males between 18 and 40 years (inclusive) of age.
- No known history of significant neurological, renal, cardiovascular, respiratory (asthma), endocrinological, gastrointestinal, hematopoietic disease, neoplasm or any other clinically significant medical disorder, which in the investigator's judgment contraindicate administration of the study medications.
- Subjects within BMI 18-29 (inclusive) calculated as Weight (Kg)/Height (m)2.
- Non-smoking (by declaration) for a period of at least 6 months.
- No history of drug or alcohol abuse.
Key exclusion criteria (19 listed)
- • Known hypersensitivity to the drug, components or other carbamates.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RivastigmineAlso: Exelon® Capsules (Novartis)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 | Drug | 1, 2, 3 |
Primary outcome
Physiological effects,Objective and subjective symptoms, Cognitive Performance tests
Time frame: 5 weeks
1 secondary outcome
4. Pharmacokinetic parameters (Cmax, Tmax, AUCT, AUCI ) determined from plasma rivastigmine concentrations,Blood cholinesterase inhibition
Time frame: 5 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
JACOB ATSMON, MD principal investigator
TASMC CLINICAL RESEARCH CENTER
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Rivastigmine in people with Rivastigmine Toxicity, run by Tel-Aviv Sourasky Medical Center at 2 sites in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Physiological effects,Objective and subjective symptoms, Cognitive Performance tests (time frame: 5 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2014.