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Evaluating the Safety, Tolerability, Pharmacokinetics and Receptor Occupancy of BMS-984923

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ClinicalTrials.gov Identifier: NCT04805983
Recruitment Status : Recruiting
First Posted : March 18, 2021
Last Update Posted : April 14, 2021
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Adam Mecca, Yale University

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

Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: BMS-984923 Phase 1

Detailed Description:
The primary objective of this study is to evaluate the safety, tolerability, and pharmacokinetics of BMS-984923 in healthy participants. A secondary objective of this study is to conduct a receptor occupancy sub-study aimed at determining drug receptor occupancy at each dose using [18F]FPEB Positron Emission Tomography.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
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)
Primary Purpose: Basic Science
Official Title: An Open-Label, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Receptor Occupancy of BMS-984923
Actual Study Start Date : March 25, 2021
Estimated Primary Completion Date : October 1, 2021
Estimated Study Completion Date : October 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 10 mg BMS-984923 Drug: BMS-984923
Day 1: Admission, administration of study drug, and 2 night in-patient stay; Day 3: Discharge following the completion of all scheduled procedures.

Experimental: 40 mg BMS-984923 Drug: BMS-984923
Day 1: Admission, administration of study drug, and 2 night in-patient stay; Day 3: Discharge following the completion of all scheduled procedures.

Experimental: 70 mg BMS-984923 Drug: BMS-984923
Day 1: Admission, administration of study drug, and 2 night in-patient stay; Day 3: Discharge following the completion of all scheduled procedures.

Experimental: 100 mg BMS-984923 Drug: BMS-984923
Day 1: Admission, administration of study drug, and 2 night in-patient stay; Day 3: Discharge following the completion of all scheduled procedures.




Primary Outcome Measures :
  1. Incidence of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 7 days after last dose ]
  2. Incidence of lab abnormalities [ Time Frame: Up to 7 days after last dose ]
  3. Incidence of clinically significant changes in safety assessments [ Time Frame: Up to 7 days after last dose ]
    Vital Signs, Physical Exam, Electrocardiogram, Neuropsychiatric Inventory - Q, Geriatric Depression Scale, Glasgow Coma Scale, Montreal Cognitive Assessment

  4. Maximum Plasma Concentration (Cmax) [ Time Frame: Up to 7 days after last dose ]
    Maximum plasma concentration as determined by pharmacokinetic modeling

  5. Time of Cmax (Tmax) [ Time Frame: Up to 7 days after last dose ]
    Time of Cmax as determined by pharmacokinetic modeling

  6. Area Under the Curve from 0 to 24h (AUC 24h) [ Time Frame: Up to 7 days after last dose ]
    Plasma drug exposure as determined by pharmacokinetic modeling


Secondary Outcome Measures :
  1. Receptor Occupancy [ Time Frame: Up to 24 hours after last dose ]
    1. Metabotropic glutamate receptor subtype 5 (mGluR5) occupancy using [18F]FPEB Positron Emission Tomography



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Ages Eligible for Study:   50 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04805983


Contacts
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Contact: Adam Mecca, MD, PhD 203-764-8100 adam.mecca@yale.edu

Locations
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United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06520
Contact: Adam Mecca, MD, PhD    203-764-8100    adam.mecca@yale.edu   
Contact: Carol Gunnoud    203-765-8110    carol.gunnoud@yale.edu   
Sponsors and Collaborators
Yale University
National Institute on Aging (NIA)
Investigators
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Principal Investigator: Adam Mecca, MD, PhD Assistant Professor of Psychiatry; Associate Director, Alzheimer's Disease Research Unit; Faculty, Alzheimer's Disease Research Center (ADRC)
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Responsible Party: Adam Mecca, Assistant Professor of Psychiatry; Associate Director, Alzheimer's Disease Research Unit; Faculty, Alzheimer's Disease Research Center (ADRC), Yale University
ClinicalTrials.gov Identifier: NCT04805983    
Other Study ID Numbers: 2000028864
1U01AG058608-01A1 ( U.S. NIH Grant/Contract )
First Posted: March 18, 2021    Key Record Dates
Last Update Posted: April 14, 2021
Last Verified: April 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders