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

Sponsor

Yale University (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04805983

Collaborator

National Institute on Aging (NIA) (NIH)

Enrollment

Location

Arms

17.2

Anticipated Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

36 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.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 :

Mar 25, 2021

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Sep 1, 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

Incidence of Treatment Emergent Adverse Events (TEAEs) [Up to 7 days after last dose]
Incidence of lab abnormalities [Up to 7 days after last dose]
Incidence of clinically significant changes in safety assessments [Up to 7 days after last dose]
Vital Signs, Physical Exam, Electrocardiogram, Neuropsychiatric Inventory - Q, Geriatric Depression Scale, Glasgow Coma Scale, Montreal Cognitive Assessment
Maximum Plasma Concentration (Cmax) [Up to 7 days after last dose]
Maximum plasma concentration as determined by pharmacokinetic modeling
Time of Cmax (Tmax) [Up to 7 days after last dose]
Time of Cmax as determined by pharmacokinetic modeling
Area Under the Curve from 0 to 24h (AUC 24h) [Up to 7 days after last dose]
Plasma drug exposure as determined by pharmacokinetic modeling

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

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
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.
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).

8 for 16 or more years of education
4 for 8-15 years of education
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University	New Haven	Connecticut	United States	06520

Sponsors and Collaborators

Yale University
National Institute on Aging (NIA)

Investigators

Principal Investigator: Adam Mecca, MD, PhD, Assistant Professor of Psychiatry; Associate Director, Alzheimer's Disease Research Unit; Faculty, Alzheimer's Disease Research Center (ADRC)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

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

First Posted:

Mar 18, 2021

Last Update Posted:

Jun 24, 2022

Last Verified:

Jun 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Alzheimer Disease

Study Results

No Results Posted as of Jun 24, 2022