Drug Drug Interaction (DDI)Phase 1NCT06632990
A Study Evaluating the Potential of BMS-984923 to Alter the Systemic Exposure of Three Orally Administered Probe Substrates
A Phase 1 study testing BMS-984923, Midazolam and Caffeine in people with Drug Drug Interaction (DDI), run by Allyx Therapeutics at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Drug Drug Interaction (DDI)
- What is being tested?
- BMS-984923, Midazolam and Caffeine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Nov 2024to 15 Oct 2025
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 21Show fewer
- 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)
- Surgical history of the GI tract affecting gastric motility or altering the GI tract (with the exception of uncomplicated appendectomy and hernia repair) (a cholecystectomy is exclusionary).
- 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.
- History of hypersensitivity to midazolam, caffeine, or dextromethorphan or any other formulation ingredients.
- Use of another investigational agent within 30 days or 5 half-lives
- Neutropenia
- Thrombocytopenia
- Has moderate or severe renal disease
Trial locations and contacts
1 site in 1 country.
United States1 site
Spaulding Clinical Research
West Bend, Wisconsin, 53095
About this study
Official title: An Open-label, Randomized, Three-arm Study Evaluating the Potential of BMS-984923 to Alter the Systemic Exposure of Three Orally Administered Probe Substrates in Healthy Adult Participants
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.
Read the detailed description
To expand the use of concomitant medications in the future, the Sponsor is performing the clinical trial ALX-923-108 to determine the net effect (inhibition and induction) of BMS-984923 repeat dosing at 3 different clinically relevant doses of BMS-984923 on the pharmacokinetics of the sensitive cytochrome P450 probe substrates caffeine (CYP1A2), dextromethorphan (CYP2D6), and midazolam (CYP3A4) and their respective metabolites as measured by systemic exposure of each probe.
- Conditions
- Drug Drug Interaction (DDI)
- Keywords
- Alzheimer's Disease, Synapses, Cognition, Neuroprotection, Neurons, mGluR5, metabolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMS-984923Drug
Also called ALX-001
oral capsules once or twice daily
MidazolamDrug
midazolam, oral, 2mg administered before study drug and after study drug
CaffeineDrug
Caffeine, oral, 100mg administered before study drug and after study drug
dextromethorphanDrug
dextromethorphan, oral, 30mg administered before study drug and after study drug
| Study group | Role | What they receive |
|---|---|---|
| 50 mg Active once daily | Experimental | Not described Receives: Drug: BMS-984923 |
| 50 mg Active twice daily | Experimental | Not described Receives: Drug: BMS-984923 |
| 100 mg Active twice daily | Experimental | Not described Receives: Drug: BMS-984923 |
| Reference drugs cocktail | Experimental | midazolam, caffeine and dextromethorphan will be administered orally Receives: Drug: Midazolam; Drug: Caffeine; Drug: dextromethorphan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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
Measured: last 96 hours
Trough plasma drug concentration at steady state
plasma concentration of BMS-984923 as determined by pharmacokinetic modeling
Measured: 21 days
Secondary outcomes (3)
Incidence of treatment-emergent adverse events (TEAEs) Safety
Safety
Measured: 30 days
Incidence of clinically significant lab abnormalities
Safety
Measured: 30 days
Incidence of clinically significant changes in safety assessments vital signs, physical exam, electrocardiogram
Safety
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2024
- Study start4 Nov 2024
- Primary completion3 Apr 2025 (estimated)
- Study completion15 Oct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Drug Drug Interaction (DDI)Studies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Allyx Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06632990
- Sponsor's protocol ID
- ALX-923-108
- Other IDs
- SB1AG087748
- Status last verified
- Feb 2025
- First submitted
- 30 Sep 2024
- Last updated
- 7 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Randomized, Three-arm Study Evaluating the Potential of BMS-984923 to Alter the Systemic Exposure of Three Orally Administered Probe Substrates in Healthy Adult Participants
- ClinicalTrials.gov ID
- NCT06632990
- Acronym / sponsor ID
- ALX-923-108
- Conditions
- Drug Drug Interaction (DDI)
- Keywords
- Alzheimer's Disease, Synapses, Cognition, Neuroprotection, Neurons, mGluR5, metabolism
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Allyx TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 4 Nov 2024 (actual)
- Primary completion
- 3 Apr 2025 (estimated)
- Study completion
- 15 Oct 2025 (estimated)
- First posted
- 9 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
To expand the use of concomitant medications in the future, the Sponsor is performing the clinical trial ALX-923-108 to determine the net effect (inhibition and induction) of BMS-984923 repeat dosing at 3 different clinically relevant doses of BMS-984923 on the pharmacokinetics of the sensitive cytochrome P450 probe substrates caffeine (CYP1A2), dextromethorphan (CYP2D6), and midazolam (CYP3A4) and their respective metabolites as measured by systemic exposure of each probe.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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 | Drug: Midazolam, Drug: Caffeine, Drug: dextromethorphanmidazolam, caffeine and dextromethorphan will be administered orally |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (21 listed)
- 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.
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-984923Also: ALX-001oral capsules once or twice daily | Drug | 100 mg Active twice daily, 50 mg Active once daily, 50 mg Active twice daily |
| Midazolammidazolam, oral, 2mg administered before study drug and after study drug | Drug | Reference drugs cocktail |
| CaffeineCaffeine, oral, 100mg administered before study drug and after study drug | Drug | Reference drugs cocktail |
| dextromethorphandextromethorphan, oral, 30mg administered before study drug and after study drug | Drug | Reference drugs cocktail |
Primary outcome
Area under the curve for the first and last 96 hours of dosing (AUC96h) as determined by PK modeling
Time frame: 24 days
Total plasma concentration of caffeine as determined by pharmacokinetic modeling
Area under the curve for the first and last 96 hours of dosing (AUC96h) as determined by PK modeling
Time frame: 24 days
Total plasma concentration of midazolam as determined by pharmacokinetic modeling
Area under the curve for the first and last 96 hours of dosing (AUC96h) as determined by PK modeling
Time frame: 24 days
Total plasma concentration of dextromethorphan as determined by pharmacokinetic modeling
Area under the curve for the last 96 hours of dosing (AUC96h)
Time frame: last 96 hours
Total plasma concentration of BMS-984923 as determined by pharmacokinetic modeling
Trough plasma drug concentration at steady state
Time frame: 21 days
plasma concentration of BMS-984923 as determined by pharmacokinetic modeling
3 secondary outcomes
Incidence of treatment-emergent adverse events (TEAEs) Safety
Time frame: 30 days
Incidence of clinically significant lab abnormalities
Time frame: 30 days
Incidence of clinically significant changes in safety assessments vital signs, physical exam, electrocardiogram
Time frame: 30 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2025.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
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, Midazolam and Caffeine in people with Drug Drug Interaction (DDI), run by Allyx Therapeutics 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 6 inclusion and 21 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: under way, not looking for participants, as of the sponsor's last update on 7 Feb 2025. 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?
This study is still under way. Results are not available in the source record yet.
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?
Area under the curve for the first and last 96 hours of dosing (AUC96h) as determined by PK modeling (time frame: 24 days). The study lists 5 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 7 Feb 2025.