Bisnorcymserine in Healthy Adult Volunteers
- Alzheimer s disease (AD) is a brain disease that impairs memory, cognitive abilities and the ability to function independently. It is the most common cause of dementia in older people. It is caused by abnormal proteins in the brain that affect how neurons communicate with each other. Researchers are looking for drugs that can slow down the disease or treat its symptoms. One drug, called bisnorcymserine (BNC), may help improve brain function and symptoms in people with AD. BNC is designed to block a chemical that affects how neurons communicate with each other. Researchers want to see how BNC works in healthy older volunteers.
- To look at how the body processes bisnorcymserine taken by mouth and how safe it is for healthy older volunteers.
- Healthy volunteers at least 55 years of age.
- Participants will be screened with a physical exam, medical history, and blood and urine tests.
- Within 3 weeks from the screening visit, participants will come to the National Institute on Aging clinical unit for a 2-night stay. On the morning of the second day, they will take either a BNC capsule or a placebo. They will not know which tablet they are taking.
- Blood samples will be collected frequently throughout the second and third days of the study visit. The last blood sample will be collected about 32 hours after taking the study capsule. Participants will have heart function tests and other exams during the visit. Once the tests are done, they will leave the clinical center.
- Participants will have a final follow-up visit about 1 week after leaving the clinical center.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Primary Purpose: Treatment
|Official Title:||Phase I, Double-Blind, Placebo-Controlled, Ascending, Single-Dose, Safety, Tolerability and Pharmacokinetic Study of Bisnorcymserine (BNC), a Highly Selective Inhibitor of Butyrylcholinesterase, in Healthy Adult Volunteers|
- Safety and tolerability [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- Pharmacokinetics [ Time Frame: 1 year ] [ Designated as safety issue: No ]
|Study Start Date:||November 2012|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Alzheimer s disease (AD) is an irreversible, progressive brain disease that slowly impairs memory and other cognitive abilities, as well as behavior and the ability to carry out tasks. It is the most common cause of dementia among older people. Alzheimer s disease is caused by deposits of abnormal proteins throughout the brain, causing neurons to lose their ability to communicate with each other effectively, and eventually die. Communication between neurons uses chemicals called neurotransmitters that are secreted from one neuron to another across a synapse. Acetylcholine (Ach) is one of the most important neurotransmitters. Damage to the Ach (-producing) system in the brain is associated with the cognitive and functional deficits in Alzheimer's disease. Restoring this deficit in the cholinergic system is one approach to treat the symptoms of Alzheimer's disease. The action of Ach in brain is stopped/ blocked mainly by two brain enzymes called cholinesterases (ChEs): acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Inhibitors of these enzymes therefore augment the activity of surviving Ach neurons in AD. All ChEs currently approved for the treatment of AD mainly inhibit AChE and, secondarily and to a varying extent, BChE activities. Nevertheless, BChE remains a viable target in AD and potent, reversible and brain-targeted BChE inhibitors have been developed (as a class of drugs called cymserine analogs). Scientists at the NIA/NIH have developed a novel BChE inhibitor called Bisnorcymserine (BNC). Pre-clinical evidence suggest that BNC may be a safe treatment for Alzheimer s disease. Based on this, we propose this first-in-human study to evaluate the safety, tolerability and pharmacokinetics of single doses of BNC tartrate administered orally to healthy volunteers aged 55 years and older using a double-blind placebo-controlled design. The proposed doses are: 20mg, 40mg, 80mg, 160mg, 270mg and 380mg given as a single oral dose. Each dose will be tested in groups of 8 subjects. Six subjects in each cohort will receive active drug and two will receive placebo. Subjects will be kept in the unit and followed clinically and with laboratory tests for adverse effects for 32 hours; they will return for a follow-up visit to assess safety in about 7 days. A Data Safety Monitoring Board will evaluate the safety and tolerability associated with each dose level before the next higher dose is tested in a new cohort. All research will be performed at the National Institute on Aging (NIA) Clinical Research Unit located on the 5th floor of MedStar Harbor Hospital.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01747213
|Contact: Vickie L Schaffner||(410) firstname.lastname@example.org|
|Contact: Dimitrios I Kapogiannis, M.D.||(410) email@example.com|
|United States, Maryland|
|National Institute on Aging, Clinical Research Unit||Recruiting|
|Baltimore, Maryland, United States, 21224|
|Contact: NIA Studies Recruitment 410-350-3941 firstname.lastname@example.org|
|Principal Investigator:||Dimitrios I Kapogiannis, M.D.||National Institute on Aging (NIA)|