A Study Evaluating the Potential of BMS-984923 to Alter the Systemic Exposure of Three Orally Administered Probe Substrates

NCT06632990 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: ALX-923-108SB1AG087748
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to learn if the investigational drug, BMS-984923 will impact the exposure and clearance of other medications when given together. Most drugs are broken down and cleared in the body via cytochrome P450 enzymes in the liver. The metabolism and clearance of certain drugs can be affected by other drugs when dosed together. To evaluate the impact of BMS-984923 on the clearance of other medications, we will investigate three known pathways which may be impacted by BMS-984923. In this study participants will take one dose of the three known medications, midazolam, caffeine and dextromethorphan together. These drugs are known to be cleared by different cytochrome P450 enzymes. Blood will be collected to evaluate the exposure and clearance of these medications and their primary metabolites. Study participants will then be administered BMS-984923 for 18-days. On the 18th Day of BMS-984923 dosing, participants will again be co-administering midazolam, caffeine and dextromethorphan. Blood will be collected again, and the concentration of each drug will be measured. We will learn in this study if BMS-984923 changes the exposure and metabolism of the known drugs. These results will inform how BMS-984923 can be administered to patients who take multiple medications.

Conditions

Drug Drug Interaction (DDI)

Keywords

Alzheimer's Disease; Synapses; Cognition; Neuroprotection; Neurons; mGluR5; metabolism

Outcome Measures

Primary Outcomes (5)

• Area under the curve for the first and last 96 hours of dosing (AUC96h) as determined by PK modeling

  Total plasma concentration of caffeine as determined by pharmacokinetic modeling

  24 days

• Area under the curve for the first and last 96 hours of dosing (AUC96h) as determined by PK modeling

  Total plasma concentration of midazolam as determined by pharmacokinetic modeling

  24 days

• Area under the curve for the first and last 96 hours of dosing (AUC96h) as determined by PK modeling

  Total plasma concentration of dextromethorphan as determined by pharmacokinetic modeling

  24 days

• Area under the curve for the last 96 hours of dosing (AUC96h)

  Total plasma concentration of BMS-984923 as determined by pharmacokinetic modeling

  last 96 hours

• Trough plasma drug concentration at steady state

  plasma concentration of BMS-984923 as determined by pharmacokinetic modeling

  21 days

Secondary Outcomes (3)

• Incidence of treatment-emergent adverse events (TEAEs) Safety

  30 days

• Incidence of clinically significant lab abnormalities

  30 days

• Incidence of clinically significant changes in safety assessments vital signs, physical exam, electrocardiogram

  30 days

Study Arms (4)

50 mg Active once daily

EXPERIMENTAL

Drug: BMS-984923

50 mg Active twice daily

EXPERIMENTAL

Drug: BMS-984923

100 mg Active twice daily

EXPERIMENTAL

Drug: BMS-984923

Reference drugs cocktail

EXPERIMENTAL

midazolam, caffeine and dextromethorphan will be administered orally

Drug: Midazolam; Drug: Caffeine; Drug: dextromethorphan

Interventions

BMS-984923 DRUG

oral capsules once or twice daily

Also known as: ALX-001

100 mg Active twice daily; 50 mg Active once daily; 50 mg Active twice daily

Midazolam DRUG

midazolam, oral, 2mg administered before study drug and after study drug

Reference drugs cocktail

Caffeine DRUG

Caffeine, oral, 100mg administered before study drug and after study drug

Reference drugs cocktail

dextromethorphan DRUG

dextromethorphan, oral, 30mg administered before study drug and after study drug

Reference drugs cocktail

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men or women between the ages of 18 and 50 years, inclusive.
• No history of cognitive impairment.
• Capable of providing written informed consent and willing to comply with all study requirements and procedures.
• Female participants, if of childbearing potential, must be non-lactating, confirmed to be non-pregnant (negative serum pregnancy test), and agree to use a highly effective form of contraception throughout the trial and for 90 days after the last dose.
• Male participants who are sexually active with a woman of childbearing potential must agree to use condoms during the study and for 90 days after the last dose unless the woman is using a highly effective form of contraception
• Compliance with restricted foods, medications, and drinks outlined within this protocol

You may not qualify if:

• Currently on any medication for a chronic condition.
• 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.
• A current DSM V diagnosis of active major depression, schizophrenia, or bipolar disorder.
• Positive urine drug screen or positive urine alcohol or alcohol breathalyzer test.
• Current use of cannabidiol / THC.
• Current nicotine use or positive urine cotinine test.
• Participants must test negative for caffeine prior to dosing.
• 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 that, in the opinion of the PI, may either put the participant at risk because of participation in the study, or influence the results, or the participant's ability to participate in the study.
• Any disorder or medication that could interfere with the absorption, distribution, metabolism or excretion of drugs (e.g., small bowel disease, Crohn's disease, celiac disease, GERD, or liver disease and antimotility or gastric acid depressing medications and weight loss medications)
• Use of medications with potential drug-drug interactions
• Is unable to refrain from the use of other prescription or non-prescription drugs
• History or presence of clinically significant ECG abnormalities
• Donation of blood or blood products for transfusion within 3 months prior to first study drug administration
• History of hypersensitivity to any of the excipients in the formulation of the study drugs.

Sponsors & Collaborators

• Allyx Therapeutics: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Spaulding Clinical Research

West Bend, Wisconsin, 53095, United States

Location

MeSH Terms

Interventions

Midazolam; Caffeine; Dextromethorphan

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Xanthines; Alkaloids; Purinones; Purines; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2024
• First Posted: October 9, 2024
• Study Start: November 4, 2024
• Primary Completion: April 3, 2025
• Study Completion: October 15, 2025
• Last Updated: February 7, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)