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| ID | Type | Description | Link |
|---|---|---|---|
| SB1AG087748 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 50 mg Active once daily | Experimental |
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| 50 mg Active twice daily | Experimental |
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| 100 mg Active twice daily | Experimental |
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| Reference drugs cocktail | Experimental | midazolam, caffeine and dextromethorphan will be administered orally |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BMS-984923 | Drug | oral capsules once or twice daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of treatment-emergent adverse events (TEAEs) Safety | Safety | 30 days |
| Incidence of clinically significant lab abnormalities | Safety |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Spaulding Clinical Research | West Bend | Wisconsin | 53095 | United States |
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| Midazolam | Drug | midazolam, oral, 2mg administered before study drug and after study drug |
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| Caffeine | Drug | Caffeine, oral, 100mg administered before study drug and after study drug |
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| dextromethorphan | Drug | dextromethorphan, oral, 30mg administered before study drug and after study drug |
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| 30 days |
| Incidence of clinically significant changes in safety assessments vital signs, physical exam, electrocardiogram | Safety | 30 days |
| ID | Term |
|---|---|
| D008874 | Midazolam |
| D002110 | Caffeine |
| D003915 | Dextromethorphan |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D014970 | Xanthines |
| D000470 | Alkaloids |
| D011688 | Purinones |
| D011687 | Purines |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
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