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Includes a placebo-controlled sequential, ascending multiple-dose panels (10 panels, 8 ascending doses, and 2 fixed Japanese Panels exploring safety, tolerability, and Pharmacokinetic (PK) measures
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Panel 1:BMS-933043(2mg)/Placebo+Antacid Buffer Solution | Experimental | BMS-933043 2 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days |
|
| Panel 2:BMS-933043(5mg)/Placebo+Antacid Buffer Solution | Experimental | BMS-933043 5 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days |
|
| Panel 3:BMS-933043(10mg)/Placebo+Antacid Buffer Solution | Experimental | BMS-933043 10 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days |
|
| Panel 4:BMS-933043(25mg)/Placebo+Antacid Buffer Solution | Experimental | BMS-933043 25 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BMS-933043 | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety and tolerability of multiple oral doses of BMS-933043 in healthy subjects measured by AEs, Vital signs, clinical laboratory test results, physical examination findings, neurological examination findings and electrocardiogram (ECG) parameters | AEs = Adverse Events | Up to Day 26 of Follow-up |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum observed plasma concentration (Cmax) | PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data | Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12 |
| Time of maximum observed plasma concentration (Tmax) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinilabs, Inc. | New York | New York | 10019 | United States |
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| Panel 5:BMS-933043(50mg)/Placebo+Antacid Buffer Solution | Experimental | BMS-933043 50 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days CSF sampling required |
|
| Panel 6:BMS-933043(100mg)/Placebo+Antacid Buffer Solution | Experimental | BMS-933043 100 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days |
|
| Panel 7:BMS-933043(200mg)/Placebo+Antacid Buffer Solution | Experimental | BMS-933043 200 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days |
|
| Panel 8:BMS-933043(25mg)/Placebo+Antacid Buffer Predose | Experimental | MAD Phase: Japanese Subjects. Cerebrospinal fluid (CSF) sampling not required BMS-933043 25 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days |
|
| Panel 9:BMS-933043(200mg)/Placebo+Antacid Buffer Predose | Experimental | Japanese Subjects. CSF sampling not required. BMS-933043 200 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days |
|
| Panel 10:BMS-933043(350mg)/Placebo+Antacid Buffer Predose | Experimental | BMS-933043 350 mg solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days |
|
| CSF Panel:BMS-933043(MTD)/Placebo+Antacid Buffer Predose | Experimental | If Panel 5 does not run. CSF Sampling at steady state BMS-933043 maximum tolerated dose (MTD), solution by mouth twice daily for 10 days OR Placebo matching with BMS-933043 0 mg solution by mouth twice daily for 10 days Antacid Buffer Predose 150 mL solution by mouth twice daily for 10 days |
|
| Placebo matching with BMS-933043 | Drug |
|
| Antacid Buffer Predose Solution | Drug |
|
PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data |
| Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12 |
| Area under the concentration-time curve in one dosing interval [AUC(TAU)] | PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data | Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12 |
| Plasma half-life (T-HALF) | PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data | Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12 |
| Trough observed plasma concentration (Cmin) between dose interval | PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data | Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12 |
| Volume of distribution at steady-state (VSS/F) of BMS-933043 | PK of BMS-933043 will be derived from plasma concentration versus time and urinary excretion data | Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12 |
| Accumulation index (AI): ratio of AUC(TAU) at steady-state to AUC(TAU) after the first dose | PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data | Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12 |
| Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR AUC(tau)] | PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data | Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12 |
| Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight [MR Cmax] | PK of BMS-933043, BMS-941651, BMS-972869 and BMS-610999 will be derived from plasma concentration versus time and urinary excretion data | Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12 |
| CSF penetration of BMS-933043 | Cerebral Spinal Fluid (CSF) will be analyzed for drug levels to confirm adequate central nervous system (CNS) penetration (>2 nM is required) and to estimate the brain/plasma ratio in humans | Day 8 |
| Effect of BMS-933043 on ECG intervals and to explore the relationship between plasma exposure and ECG intervals | The effects of BMS-933043 on ECG parameters (heart rate, QTcF, PR, and QRS) will be explored graphically and by summary statistics. Absolute levels, as well as changes from baseline, will be summarized and plotted versus time by treatment and day for each ECG parameter. Frequency distributions for subjects' maximum values will be provided by treatment. The relationships between ECG parameters and BMS-933043 concentrations may be explored using scatter plots and the relationship between the change from baseline in QTcF and the BMS-933043 concentration may be estimated | Baseline (Day -2), Day 1, Day 6 and Day 10 |
| Safety and tolerability of multiple oral doses of BMS-9333043 in Japanese healthy subjects is measured by AEs, Vital signs, clinical laboratory test results, physical examination findings, neurological examination findings and ECG parameters | Up to 6 months |
| Effect of ethnicity (Japanese versus non-Japanese) on PK of BMS-933043 will be assessed graphically and by point estimates and 90% confidence intervals for geometric mean ratio for Cmax using data from subjects receiving the same dose of BMS-933043 | Day 1, Day 3, Day 6, Day 9, Day 10, Day 11 and Day 12 |
| ID | Term |
|---|---|
| C000621716 | BMS-933043 |
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