Bisnorcymserine in Healthy Adult Volunteers

NCT01747213 | Completed Phase 1 FDA Drug

• 2 other identifiers: 13003413-AG-0034
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Healthy Volunteers

Keywords

Clinical Trial; Alzheimer Disease; Healthy Volunteers; Neurotransmitters

Outcome Measures

Primary Outcomes (1)

• 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.

  Will be completed in one year

Secondary Outcomes (1)

• pharmacokinetic profile (parameters)

  Will be completed in one year

Study Arms (2)

BNC

EXPERIMENTAL

Bisnorcymserine tartrate

Drug: BNC

Placebo

PLACEBO COMPARATOR

microcrystalline celluose

Other: Placebo

Interventions

BNC DRUG

BNC

Placebo OTHER

Microcrystalline cellulose fiber

Placebo

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• National Institute on Aging (NIA): lead

Study Sites (2)

National Institute on Aging, Clinical Research Unit

Baltimore, Maryland, 21224, United States

Location

Harbor Hospital Center

Baltimore, Maryland, United States

Location

Related Publications (3)

• 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.

  PMID: 6140490 BACKGROUND

• Cummings JL. Use of cholinesterase inhibitors in clinical practice: evidence-based recommendations. Am J Geriatr Psychiatry. 2003 Mar-Apr;11(2):131-45.

  PMID: 12611743 BACKGROUND

• Darvesh 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.

  PMID: 9548556 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Dimitrios I Kapogiannis, M.D.

  National Institute on Aging (NIA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2012
• First Posted: December 11, 2012
• Study Start: January 29, 2013
• Primary Completion: September 21, 2018
• Study Completion: January 8, 2019
• Last Updated: April 14, 2026

Record last verified: 2026-03-17

Locations

US (2)