Healthy VolunteersPhase 1NCT01747213
Bisnorcymserine in Healthy Adult Volunteers
A Phase 1 study testing BNC in people with Healthy Volunteers, run by National Institute on Aging (NIA) at 2 sites in United States.
Trial summary
Background: 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. Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- BNC
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 2 sitesUnited States
- Study dates
- 29 Jan 2013to 8 Jan 2019
- Phase
- Phase 1
- 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 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age greater than or equal to 55 years.
- Mini Mental State Examination (MMSE) > 27 at screening and at Visit 2-Day 1.
- Women who are able to become pregnant must have a negative urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) at screening and prior to study drug administration
- Both men who are able to father children and women of childbearing potential must be willing to use an adequate method of contraception (see section 7) to avoid conception throughout the study and for up to 30 days of study drug administration.
- Body mass index (BMI) of 18.5 to 34.0, inclusive, and a total body weight of > 50 kg (110 pounds).
- Participants should be in good general physical and mental health as determined by medical history, a baseline physical examination, vital signs, clinical laboratory tests and electrocardiogram (EKG). Participants may have common age-related disorders (such as hypertension, type II diabetes, dyslipidemia, hypothyroidism) as long as these disorders are under good control by diet or medications.
- Able to sign own consent
Who cannot join
- Any clinically significant medical and psychiatric condition (including asthma active within the last 10 years or COPD, and drug abuse and dependency).
- Subject has used any tobacco products in the past 3 months.
- A history of significant allergy to any drug or systemic allergic disease (e.g., urticaria, atopic dermatitis).
- Pregnant or lactating females.
- Subject with a positive urine test for drugs of abuse at screening or at admission to the clinic on study Day 1.
- Subject has consumed any alcohol within 48 hours prior to Visit 2; and cannot or is unwilling, thereafter to abstain from drinking alcohol for the remainder of the subject s study participation.
Show all 31Show fewer
- Subject is positive for HIV, hepatitis B surface antigen or hepatitis C antibody tests at screening.
- Any clinically significant laboratory abnormality. These include:
- CBC: WBC < 3000 /mm^3; Hb < 12 g/dL; Liver function tests: ALT, AST, Bilirubin (total, direct, indirect), Alkaline Phosphatase > 1.5 x the upper normal limit of the laboratory
- Serum Creatinine > 1.5 mg/dL; Serum Glucose >150mg/dL
- Resting supine blood pressure outside of a systolic blood pressure range of 90-140 mmHg or a diastolic blood pressure outside a range of 50-90 mmHg on two consecutive measurements taken up to 10 minutes apart.Resting supine heart rate greater than 100 bpm or less than or equal to 55 55 bpm on two consecutive measurements taken up to 10 minutes apart.
- Any clinically significant abnormality on screening 12-lead EKG (e.g., heart block, conduction disorders, ventricular and/or atrial arrhythmias).
- Routine or PRN consumption of the following herbal/dietary supplements are not permitted, if used within 2 weeks before the screening visit at doses higher than the recommended daily intake: Omega-3 fatty acids (> 1000 mg/day), Vitamin E (> 400IU/day). Ginkgo biloba, St. John's wort and ginseng are not permitted, if used at any dose within 2 weeks before the screening visit.
- Medications that are excluded are:
- Insulin
- Anti-parkinsonian medications (such as levodopa/carbidopa, amantadine, bromocriptine, pergolide, selegiline)
- Typical or atypical neuroleptics
- Narcotic analgesics at any dose within 4 weeks prior to screening.
- Long-acting benzodiazepines or barbiturates (such as clonazepam, diazepam, phenobarbital) within 4 weeks prior to screening
- Short-acting anxiolytics or sedative hypnotics more frequently than 2 times per week within 4 weeks prior to screening (sedative hypnotics should not be used within 102 hours of study drug administration)
- Medications with known significant cholinergic or anticholinergic side effects (such as pyridostigmine, tricyclic antidepressants, meclizine, oxybutynin) within 4 weeks prior to screening
- Anti-convulsants (such as phenytoin, Phenobarbital, carbamazepine) within 2 months prior to screening
- Medications for Alzheimer s disease (such as donepezil or memantine)
- Beta-Blockers
- Corticosteroids (Systemic)
- Neuromuscular-Blocking Agents (non-depolarizing)
- Succinylcholine
- Any other drug (including prescription, over the counter medications and supplements) that may pose a risk to the subject or produce overlapping side effects with the study medication. Participants will not be taken off of medications for the purpose of this study.
- Donation or loss of 400 mL or more of blood within 56 days prior to and subsequent to screening.
- Participation in another research study involving an investigational drug within 30 days or 5 half-lives, whichever is longer.
- Known allergy or hypersensitivity to the investigational study drug and to the microcrystalline cellulose used as placebo.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
National Institute on Aging, Clinical Research Unit
Baltimore, Maryland, 21224
Harbor Hospital Center
Baltimore, Maryland
About this study
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
Background:
- 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.
Read more
Objectives:
- To look at how the body processes bisnorcymserine taken by mouth and how safe it is for healthy older volunteers.
Eligibility:
- Healthy volunteers at least 55 years of age.
Design:
- 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.
Read the detailed description
Objective: Alzheimer s disease (AD) is a progressive neurodegenerative disease that impairs memory and other cognitive abilities, as well as behavior and the ability to function independently. It is the most common cause of dementia among older people. Alzheimer s disease is characterized by deficits in several neurotransmitter systems, most prominently acetylcholine (Ach). The cholinergic deficit in the AD brain is associated with the cognitive and functional symptoms in AD. Restoring this deficit in the cholinergic system is one proven approach for symptomatic treatment in AD. The action of Ach in the brain is terminated mainly by two 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 inhibitors currently approved for the treatment of AD mainly inhibit AChE and, secondarily and to a varying extent, BChE. Reversible and brain-specific 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 suggests 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.
Study population: Healthy volunteers aged 55 years and older.
Design: Double blind placebo-controlled Phase I clinical Trial of single oral doses of BNC doses in an ascending schedule: 20, 40mg, 80 mg, 120 mg, 160 mg, 270 mg and 380 mg. 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.
- Conditions
- Healthy Volunteers
- Being tested
- BNC, Placebo
- Keywords
- Clinical Trial, Alzheimer Disease, Healthy Volunteers, Neurotransmitters
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BNCDrug
PlaceboOther
Microcrystalline cellulose fiber
| Study group | Role | What they receive |
|---|---|---|
| BNC | Experimental | Bisnorcymserine tartrate Receives: Drug: BNC |
| Placebo | Placebo comparator | microcrystalline celluose Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability
Safety and tolerability will be determined based on the frequency of AEs of any grade in BNC and placebo groups. AEs will be determined based on clinical symptoms and signs, vital signs, safety laboratory tests, EKG and continuous cardiac monitoring, MMSE, and C-SSRS.
Measured: Will be completed in one year
Secondary outcomes (1)
pharmacokinetic profile (parameters)
The pharmacokinetic profile of a single oral dose of BNC in a capsule will be determined, including evaluation of AUC, Tmax, Cmax, elimination rate constant, T1/2, clearance and volume of distribution. In addition, we will measure pharmacodynamics parameters, including acetyl-cholinesterase and butyryl-cholinesterase activity
Measured: Will be completed in one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2012 (estimated)
- Study start29 Jan 2013
- Primary completion21 Sep 2018
- Study completion8 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Aging (NIA)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Dimitrios I Kapogiannis, M.D., Principal investigator, National Institute on Aging (NIA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01747213
- Sponsor's protocol ID
- 130034
- Other IDs
- 13-AG-0034
- Status last verified
- 17 Mar 2026
- First submitted
- 8 Dec 2012
- Last updated
- 5 Nov 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: There is ongoing discussion within the NIA IRP and a plan has not been finalized yet.
Publications
Arendt T, Bigl V, Walther F, Sonntag M. Decreased ratio of CSF acetylcholinesterase to butyrylcholinesterase activity in Alzheimer's disease. Lancet. 1984 Jan 21;1(8369):173. doi: 10.1016/s0140-6736(84)90116-8. No abstract available.
PubMed 6140490Cummings JL. Use of cholinesterase inhibitors in clinical practice: evidence-based recommendations. Am J Geriatr Psychiatry. 2003 Mar-Apr;11(2):131-45.
PubMed 12611743Darvesh S, Grantham DL, Hopkins DA. Distribution of butyrylcholinesterase in the human amygdala and hippocampal formation. J Comp Neurol. 1998 Apr 13;393(3):374-90.
PubMed 9548556Tzieras I, Manolopoulos A, Tweedie D, Luo W, Maccecchini M, Egan JM, Greig NH, Kapogiannis D. A phase 1, safety, tolerability, and pharmacokinetics study of bisnorcymserine, a highly selective inhibitor of butyrylcholinesterase. Neurotherapeutics. 2026 Apr;23(3):e00918. doi: 10.1016/j.neurot.2026.e00918. Epub 2026 May 13.
PubMed 42127455
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01747213
- Acronym / sponsor ID
- 130034
- Conditions
- Healthy Volunteers
- Keywords
- Clinical Trial, Alzheimer Disease, Healthy Volunteers, Neurotransmitters
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- National Institute on Aging (NIA)US National Institutes of Health
- Study start
- 29 Jan 2013 (actual)
- Primary completion
- 21 Sep 2018 (actual)
- Study completion
- 8 Jan 2019 (actual)
- First posted
- 11 Dec 2012 (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.
Background:
- 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.
Objectives:
- To look at how the body processes bisnorcymserine taken by mouth and how safe it is for healthy older volunteers.
Eligibility:
- Healthy volunteers at least 55 years of age.
Design:
- 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.
Detailed description
Objective: Alzheimer s disease (AD) is a progressive neurodegenerative disease that impairs memory and other cognitive abilities, as well as behavior and the ability to function independently. It is the most common cause of dementia among older people. Alzheimer s disease is characterized by deficits in several neurotransmitter systems, most prominently acetylcholine (Ach). The cholinergic deficit in the AD brain is associated with the cognitive and functional symptoms in AD. Restoring this deficit in the cholinergic system is one proven approach for symptomatic treatment in AD. The action of Ach in the brain is terminated mainly by two 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 inhibitors currently approved for the treatment of AD mainly inhibit AChE and, secondarily and to a varying extent, BChE. Reversible and brain-specific 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 suggests 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.
Study population: Healthy volunteers aged 55 years and older.
Design: Double blind placebo-controlled Phase I clinical Trial of single oral doses of BNC doses in an ascending schedule: 20, 40mg, 80 mg, 120 mg, 160 mg, 270 mg and 380 mg. 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BNC | Experimental | Drug: BNCBisnorcymserine tartrate |
| Placebo | Placebo comparator | Other: Placebomicrocrystalline celluose |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age greater than or equal to 55 years.
- Mini Mental State Examination (MMSE) > 27 at screening and at Visit 2-Day 1.
- Women who are able to become pregnant must have a negative urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) at screening and prior to study drug administration
- Both men who are able to father children and women of childbearing potential must be willing to use an adequate method of contraception (see section 7) to avoid conception throughout the study and for up to 30 days of study drug administration.
- Body mass index (BMI) of 18.5 to 34.0, inclusive, and a total body weight of > 50 kg (110 pounds).
Key exclusion criteria (31 listed)
- Any clinically significant medical and psychiatric condition (including asthma active within the last 10 years or COPD, and drug abuse and dependency).
- Subject has used any tobacco products in the past 3 months.
- A history of significant allergy to any drug or systemic allergic disease (e.g., urticaria, atopic dermatitis).
- Pregnant or lactating females.
- Subject with a positive urine test for drugs of abuse at screening or at admission to the clinic on study Day 1.
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 |
|---|---|---|
| BNC | Drug | BNC |
| PlaceboMicrocrystalline cellulose fiber | Other | Placebo |
Primary outcome
Safety and Tolerability
Time frame: Will be completed in one year
Safety and tolerability will be determined based on the frequency of AEs of any grade in BNC and placebo groups. AEs will be determined based on clinical symptoms and signs, vital signs, safety laboratory tests, EKG and continuous cardiac monitoring, MMSE, and C-SSRS.
1 secondary outcome
pharmacokinetic profile (parameters)
Time frame: Will be completed in one year
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 5 Nov 2026.
- Background: PubMed 6140490Arendt T, Bigl V, Walther F, Sonntag M. Decreased ratio of CSF acetylcholinesterase to butyrylcholinesterase activity in Alzheimer's disease. Lancet. 1984 Jan 21;1(8369):173. doi: 10.1016/s0140-6736(84)90116-8. No abstract available.
- Background: PubMed 12611743Cummings JL. Use of cholinesterase inhibitors in clinical practice: evidence-based recommendations. Am J Geriatr Psychiatry. 2003 Mar-Apr;11(2):131-45.
- Background: PubMed 9548556Darvesh S, Grantham DL, Hopkins DA. Distribution of butyrylcholinesterase in the human amygdala and hippocampal formation. J Comp Neurol. 1998 Apr 13;393(3):374-90.
- Derived from this study: PubMed 42127455Tzieras I, Manolopoulos A, Tweedie D, Luo W, Maccecchini M, Egan JM, Greig NH, Kapogiannis D. A phase 1, safety, tolerability, and pharmacokinetics study of bisnorcymserine, a highly selective inhibitor of butyrylcholinesterase. Neurotherapeutics. 2026 Apr;23(3):e00918. doi: 10.1016/j.neurot.2026.e00918. Epub 2026 May 13.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. There is ongoing discussion within the NIA IRP and a plan has not been finalized yet.
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Screening Protocol
Pain
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.
Dimitrios I Kapogiannis, M.D. principal investigator
National Institute on Aging (NIA)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BNC in people with Healthy Volunteers, run by National Institute on Aging (NIA) at 2 sites in United States.
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 7 inclusion and 31 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 5 Nov 2026. 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 United States. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Safety and Tolerability (time frame: Will be completed in one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01747213, which also lists 4 linked publications.
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 5 Nov 2026.