Alzheimer DiseasePhase 1NCT04805983
Evaluating the Safety, Tolerability, Pharmacokinetics and Receptor Occupancy of BMS-984923
A Phase 1 study testing BMS-984923 in people with Alzheimer Disease, run by Yale University at 1 site in United States.
Trial summary
This project seeks to develop a novel disease-modifying compound for Alzheimer's disease (AD). Read more about this study
- Who is it for?
- Ages 50 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- BMS-984923
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Mar 2021to 24 Apr 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 50 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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. -
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- 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
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-Label, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Receptor Occupancy of BMS-984923
This project seeks to develop a novel disease-modifying compound for Alzheimer's disease (AD).
Read the 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.
- Conditions
- Alzheimer Disease
- Being tested
- BMS-984923
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMS-984923Drug
Day 1: Admission, administration of study drug, and 2 night in-patient stay; Day 3: Discharge following the completion of all scheduled procedures.
| Study group | Role | What they receive |
|---|---|---|
| 10 mg BMS-984923 | Experimental | Not described Receives: Drug: BMS-984923 |
| 40 mg BMS-984923 | Experimental | Not described Receives: Drug: BMS-984923 |
| 70 mg BMS-984923 | Experimental | Not described Receives: Drug: BMS-984923 |
| 100 mg BMS-984923 | Experimental | Not described Receives: Drug: BMS-984923 |
| 150 mg BMS-984923 | Experimental | Not described Receives: Drug: BMS-984923 |
| 200 mg BMS-984923 | Experimental | Not described Receives: Drug: BMS-984923 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Count of Treatment Emergent Adverse Events (TEAEs)
A count of participants that experience any adverse events found to be associated with treatment. All adverse events are summarized in the adverse events section.
Measured: Up to 7 days after last dose
Count of Lab Abnormalities
Count of participants with clinical lab abnormalities.
Measured: Up to 7 days after last dose
Count of Clinically Significant Changes in Safety Assessments
A count of participants that experienced any clinically significant changes in: Vital Signs, Physical Exam, Electrocardiogram, Neuropsychiatric Inventory - Q, Geriatric Depression Scale, Glasgow Coma Scale, Montreal Cognitive Assessment
Measured: Up to 7 days after last dose
Maximum Plasma Concentration (Cmax)
Maximum plasma concentration as determined by pharmacokinetic modeling
Measured: Up to 7 days after last dose
Time of Cmax (Tmax)
Time of Cmax as determined by pharmacokinetic modeling
Measured: Up to 7 days after last dose
Area Under the Curve From 0 to 24h (AUC 24h)
Plasma drug exposure as determined by pharmacokinetic modeling, AUC is represented as ng∙h/mL.
Measured: Up to 7 days after last dose
Secondary outcomes (1)
Receptor Occupancy
Metabotropic glutamate receptor subtype 5 (mGluR5) occupancy using [18F]FPEB Positron Emission Tomography calculated using the percentage of total mGluR5 availability and plasma concentrations of study drug were used to model the relationship between plasma concentration (CP) and receptor occupancy with the conventional sigmoidal maximum receptor occupancy (r_max) model where IC50 is the CP required to produce 50% of the r_max. A nonlinear least squares analysis was used to estimate the parameters from all scans. The data supported a model with 1 parameter (IC50, r_max = 100%). IC80 is the CP required to produce 80% of the r_max. The outcomes of relevance are the IC50 and IC80 calculated for the model.
Measured: Up to 24 hours after last dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2021
- Study start25 Mar 2021
- Primary completion24 Apr 2022
- Study completion24 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Adam Mecca, Yale University
- Investigators
- Adam Mecca, MD, PhD, Principal investigator, Assistant Professor of Psychiatry; Associate Director, Alzheimer's Disease Research Unit; Faculty, Alzheimer's Disease Research Center (ADRC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04805983
- Sponsor's protocol ID
- 2000028864
- Other IDs
- 1U01AG058608-01A1
- Status last verified
- Jul 2024
- First submitted
- 14 Mar 2021
- Last updated
- 27 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Receptor Occupancy of BMS-984923
- ClinicalTrials.gov ID
- NCT04805983
- Acronym / sponsor ID
- 2000028864
- Conditions
- Alzheimer Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 25 Mar 2021 (actual)
- Primary completion
- 24 Apr 2022 (actual)
- Study completion
- 24 Apr 2022 (actual)
- First posted
- 18 Mar 2021 (actual)
- Results
- Posted 13 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This project seeks to develop a novel disease-modifying compound for Alzheimer's disease (AD).
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
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
- 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.
| Arm | Type | Receives |
|---|---|---|
| 10 mg BMS-984923 | Experimental | Drug: BMS-984923 |
| 40 mg BMS-984923 | Experimental | Drug: BMS-984923 |
| 70 mg BMS-984923 | Experimental | Drug: BMS-984923 |
| 100 mg BMS-984923 | Experimental | Drug: BMS-984923 |
| 150 mg BMS-984923 | Experimental | Drug: BMS-984923 |
| 200 mg BMS-984923 | Experimental | Drug: BMS-984923 |
Who may qualify
- Ages
- 50 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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
- Glasgow Coma Scale Score of 15 (97)
- Clinical Dementia Rating Score of 0 (93)
Key exclusion criteria (17 listed)
- 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.
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 |
|---|---|---|
| BMS-984923Day 1: Admission, administration of study drug, and 2 night in-patient stay; Day 3: Discharge following the completion of all scheduled procedures. | Drug | 10 mg BMS-984923, 100 mg BMS-984923, 150 mg BMS-984923, 200 mg BMS-984923, 40 mg BMS-984923, 70 mg BMS-984923 |
Primary outcome
Count of Treatment Emergent Adverse Events (TEAEs)
Time frame: Up to 7 days after last dose
A count of participants that experience any adverse events found to be associated with treatment. All adverse events are summarized in the adverse events section.
Count of Lab Abnormalities
Time frame: Up to 7 days after last dose
Count of participants with clinical lab abnormalities.
Count of Clinically Significant Changes in Safety Assessments
Time frame: Up to 7 days after last dose
A count of participants that experienced any clinically significant changes in: Vital Signs, Physical Exam, Electrocardiogram, Neuropsychiatric Inventory - Q, Geriatric Depression Scale, Glasgow Coma Scale, Montreal Cognitive Assessment
Maximum Plasma Concentration (Cmax)
Time frame: Up to 7 days after last dose
Maximum plasma concentration as determined by pharmacokinetic modeling
Time of Cmax (Tmax)
Time frame: 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)
Time frame: Up to 7 days after last dose
Plasma drug exposure as determined by pharmacokinetic modeling, AUC is represented as ng∙h/mL.
1 secondary outcome
Receptor Occupancy
Time frame: Up to 24 hours after last dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Adam Mecca, MD, PhD principal investigator
Assistant Professor of Psychiatry; Associate Director, Alzheimer's Disease Research Unit; Faculty, Alzheimer's Disease Research Center (ADRC)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BMS-984923 in people with Alzheimer Disease, run by Yale University at 1 site 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 17 inclusion and 17 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 27 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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?
Yes. Results are posted in the registry (first posted 13 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Count of Treatment Emergent Adverse Events (TEAEs) (time frame: Up to 7 days after last dose). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Aug 2024.