Evaluating the Safety, Tolerability, Pharmacokinetics and Receptor Occupancy of BMS-984923
Condition: Alzheimer Disease
MeSH terms: Alzheimer Disease
Intervention: BMS-984923
Intervention description: Day 1: Admission, administration of study drug, and 2 night in-patient stay; Day 3: Discharge following the completion of all scheduled procedures.
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: The study will enroll four cohorts of 6 participants each. Study drug will be administered in sequentially increasing dose groups. For all 6 participants at a dose cohort, a safety assessment review will be completed prior to advancing the next higher dose level.
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 50 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This project seeks to develop a novel disease-modifying compound for Alzheimer's disease
      (AD).
    

Eligibility criteria:

        Inclusion Criteria:

          -  No history of cognitive impairment

          -  Capable of providing written informed consent and willing to comply with all study
             requirements and procedures

          -  Participant is not pregnant, lactating, or of childbearing potential

               1. Non-childbearing potential for women is defined as postmenopausal (last natural
                  menses greater than 24 months; menopausal status will be documented with serum
                  follicle stimulating hormone (FSH) or documentation of bilateral tubal ligation
                  or hysterectomy

               2. Male participants who are sexually active with a woman of child-bearing potential
                  must agree to use condoms during the trial and for 3 months after the last dose
                  unless the woman is using an acceptable means of birth control. Acceptable forms
                  of birth control include abstinence, birth control pills, or any double
                  combination of: intrauterine device (IUD), male or female condom, diaphragm,
                  sponge, and cervical cap.

               3. Male participants must also agree not to donate sperm for 90 days after the last
                  dose. -

          -  Glasgow Coma Scale Score of 15 (97)

          -  Clinical Dementia Rating Score of 0 (93)

          -  Has a reliable study partner who has frequent contact with the participant (e.g.,
             average of 10 hours per week or more), who can be available for study partner
             assessments, who can accompany the participant for 48 hours, without absence, after
             discharge from Visit 2.

        Score on the Mini Mental Status Exam > 26 (95)

          -  Objective memory scores within normal range for age evidenced by a score no more than
             1.5 standard deviations below the education adjusted cutoff on the Logical Memory II
             subscale (Delayed Paragraph Recall) from the Wechsler Memory Scale - Revised (the
             maximum score is 25).

               1. >8 for 16 or more years of education

               2. >4 for 8-15 years of education

               3. >2 for 0-7 years of education

        Receptor Occupancy Substudy Eligibility Criteria

          -  Eligibility for and enrollment in Main Study

          -  Participant consent to the optional substudy

        Exclusion Criteria:

          -  Body mass index (BMI) ≥ 35 kg/m2 or body weight < 50 kg.

          -  Significant cerebrovascular disease: Modified Hachinski score > 4.

          -  Any significant neurologic disease, such as AD, Parkinson's disease, multi-infarct
             dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor,
             progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple
             sclerosis, or history of significant head trauma followed by persistent neurologic
             defaults or known structural brain abnormalities.

          -  Major depression, bipolar disorder as described in DSM-IV within the past 1 year.

          -  Psychotic features, agitation or behavioral problems within 3 months, which could lead
             to difficulty complying with the protocol.

          -  History of schizophrenia (DSM IV criteria).

          -  History of alcohol or substance abuse or dependence within the past 2 years (DSM IV
             criteria).

          -  Clinically significant or unstable medical condition, including uncontrolled
             hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal,
             hepatic, endocrine, or other systemic disease in the opinion of the PI, may either put
             the patient at risk because of participation in the study, or influence the results,
             or the patient's ability to participate in the study.

          -  Clinically significant abnormalities in B12 or Thyroid Function Tests that might
             interfere with the study.

        Use of psychoactive medications (typical neuroleptics, narcotic analgesics,
        antiparkinsonian medications, systemic corticosteroids, or medications with significant
        central anticholinergic activity) within 2 weeks or 5 half-lives (whichever is greater)
        prior to study drug administration and for the duration of the trial.

          -  Use of medications with significant CYP1A2, 2D6, or 3A4 inhibitor or inducer activity
             (See appendix for a list of these medications) within 2 weeks or 5 half-lives
             (whichever is greater) prior to study drug administration and for the duration of the
             trial.

          -  Use of anticoagulants within 30 days or 5 half-lives (whichever is greater) prior to
             study drug administration and for the duration of the trial.

          -  Use of investigational amyloid lowering therapies within 2 months prior to study drug
             administration and for the duration of the trial.

          -  Use of another investigational agent within 30 days or 5 half-lives (whichever is
             greater) prior to screening and for the duration of the trial.

          -  Neutropenia defined as absolute neutrophils count of < 1,500/microliter.

          -  Thrombocytopenia defined as platelet count < 100,000/microliter.

          -  Clinically significant abnormalities in screening laboratories, including Aspartate
             aminotransferase (AST) >1.5 times upper limit of normal (ULN); Alanine
             aminotransferase (ALT) >1.5 times ULN; Total bilirubin >1.5 times ULN; Serum
             creatinine >2.0 times ULN.