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Part A of the study will test the safety, the amount of drug in the body, and effects of the drug in the body after multiple doses. This will be conducted in healthy overweight adults. Part B of the study will test the effects of multiple doses of the investigational drug on the amount of midazolam, an approved drug, in healthy adults.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A Cohort 1 | Experimental |
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| Part A Cohort 2 | Experimental |
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| Part A Cohort 3 | Experimental |
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| Part A Cohort 4 | Experimental |
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| Part A Cohort 5 | Experimental |
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| Part B Cohort 1 | Experimental |
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| Part B Cohort 2 | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-06282999 | Drug | Tablet, 10 mg, every 8 hours, 14 days |
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| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | Pre-dose,0.5,1,2,3,4,5,6,7,8 and 16 hrs post morning dose Day 1 Part A | |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Pre-dose,0.5,1,2,3,4,5,6,7,8 and 16 hrs post morning dose Day 1 Part A | |
| Area Under the Curve from Time Zero to end of dosing interval (AUCtau) | Pre-dose,0.5,1,2,3,4,5,6,7,8 and 16 hrs post morning dose Day 1 Part A | |
| Apparent Oral Clearance (CL/F) | Pre-dose,0.5,1,2,3,4,5,6,7,8 and 16 hrs post morning dose Day 1 Part A | |
| Maximum Observed Plasma Concentration (Cmax) | Pre-dose,0.5,1,2,3,4,5,6,7,8,10,12,16,24,36, and 48 hrs post morning dose Day 14 Part A | |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Pre-dose,0.5,1,2,3,4,5,6,7,8,10,12,16,24,36, and 48 hrs post morning dose Day 14 Part A | |
| Area Under the Curve from Time Zero to end of dosing interval (AUCtau) | Pre-dose,0.5,1,2,3,4,5,6,7,8,10,12,16,24,36, and 48 hrs post morning dose Day 14 Part A | |
| Minimum Observed Plasma Trough Concentration (Cmin) | Pre-dose,0.5,1,2,3,4,5,6,7,8,10,12,16,24,36, and 48 hrs post morning dose Day 14 Part A | |
| Apparent Oral Clearance (CL/F) | Pre-dose,0.5,1,2,3,4,5,6,7,8,10,12,16,24,36, and 48 hrs post morning dose Day 14 Part A |
| Measure | Description | Time Frame |
|---|---|---|
| Diastolic Blood Pressure | Mean 24-hour average diastolic blood pressure | Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A |
| Diastolic Blood Pressure | Mean 24-hour average diastolic blood pressure |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pfizer Investigational Site | Brussels | B-1070 | Belgium |
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| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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| Placebo |
| Drug |
Tablet, 0 mg, every 8 hours, 14 days |
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| PF-06282999 | Drug | Tablet, 30 mg, every 8 hours, 14 days |
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| Placebo | Drug | Tablet, 0 mg, every 8 hours, 14 days |
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| PF-06282999 | Drug | Tablet, 100 mg, every 8 hours, 14 days |
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| Placebo | Drug | Tablet, 0 mg, every 8 hours, 14 days |
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| PF-06282999 | Drug | Tablet, 250 mg, every 8 hours, 14 days |
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| Placebo | Drug | Tablet, 0 mg, every 8 hours, 14 days |
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| PF-06282999 | Drug | Tablet, 350 mg every 8 hours or 500 mg every 12 hours, 14 days |
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| Placebo | Drug | Tablet, 0 mg, every 8 or 12 hours, 14 days |
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| midazolam | Drug | Tablet, 7.5 mg, single dose on Period 1 Day 1 and Period 2 Day 14 |
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| PF-06282999 | Drug | Tablet, dose to be determined (determined in Part A), every 8 or 12 hours, 14 days |
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| midazolam | Drug | Tablet, 7.5 mg, single dose on Period 1 Day 1 and Period 2 Day 14 |
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| PF-06282999 | Drug | Tablet, dose to be determined (determined in Part A), every 8 or 12 hours, 14 days |
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| Plasma Decay Half-Life (t1/2) | Pre-dose,0.5,1,2,3,4,5,6,7,8,10,12,16,24,36, and 48 hrs post morning dose Day 14 Part A |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) Midazolam | Pre-dose,0.5,1,2,3,4,5,6,8,10,12 and 16 hrs post dose Day 1 Period 1 Part B |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) Midazolam | -2,-1.5,-1,Pre-dose,1,2,4,6,8,10,14 Day 14 Period 2 Part B |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] | AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8). Midazolam | Pre-dose,0.5,1,2,3,4,5,6,8,10,12 and 16 hrs post dose Day 1 Period 1 Part B |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - 8)] | AUC (0 - 8)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - 8). It is obtained from AUC (0 - t) plus AUC (t - 8). Midazolam | -2,-1.5,-1,Pre-dose,1,2,4,6,8,10,14 Day 14 Period 2 Part B |
| Maximum Observed Plasma Concentration (Cmax) | Pre-dose,0.5,1,2,3,4,5,6,8,10,12 and 16 hrs post dose Day 1 Period 1 Part B |
| Maximum Observed Plasma Concentration (Cmax) | -2,-1.5,-1,Pre-dose,1,2,4,6,8,10,14 Day 14 Period 2 Part B |
| Average Concentration (Cav) | Pre-dose,0.5,1,2,3,4,5,6,7,8,10,12,16,24,36, and 48 hrs post morning dose Day 14 Part A |
| Accumulation Ratio | Pre-dose,0.5,1,2,3,4,5,6,7,8,10,12,16,24,36, and 48 hrs post morning dose Day 14 Part A |
| Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A |
| Systolic Blood Pressure | Mean 24-hour average systolic blood pressure | Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A |
| Systolic Blood Pressure | Mean 24-hour average systolic blood pressure | Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part A |
| interleukin-6 | Days 1 and 14 pre-dose Part A |
| high-sensitivity C-reactive protein | Days 1 and 14 pre-dose Part A |
| total cholesterol, HDL-C, triglycerides and calculated LDL-C | Days 1 and 14 pre-dose Part A |
| ApoBTotal,ApoB48, ApoB100, ApoA-1 | Days 1 and 14 pre-dose Part A |
| Diastolic Blood Pressure | Mean 24-hour average diastolic blood pressure | Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B |
| Diastolic Blood Pressure | Mean 24-hour average diastolic blood pressure | Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B |
| Systolic Blood Pressure | Mean 24-hour average systolic blood pressure | Day 1 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B |
| Systolic Blood Pressure | Mean 24-hour average systolic blood pressure | Day 13 Pre-dose,1,2,4,8,12 and 16 hrs post dose Part B |
| ID | Term |
|---|---|
| C000605149 | 2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide |
| D008874 | Midazolam |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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