TriangleNCT00721734 · OUTCOME
Clearance (CL) of Carfilzomib on Day 1 of Cycle 1
Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.
- Measure
- MEAN
- Unit
- liters/hour
- Interval / dispersion
- Standard Deviation
- Time frame
- Cycle 1, Day 1 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.
What was measured
Plasma concentrations of carfilzomib was determined by a validated liquid chromatography tandem mass spectrometry (LC MS/MS) method. The lower limit of quantitation (LLOQ) was 0.300 ng/mL. Concentration values that were below the LLOQ (BLQ) were set to zero. Pharmacokinetic (PK) parameters were calculated from the individual plasma concentrations of carfilzomib using a noncompartmental method.
Analysis population: The pharmacokinetic (PK) evaluable population includes participants with stable baseline renal function (Arms 1-4) who completed all protocol-specified treatment and PK blood sample collection through Cycle 1, Day 16. In Group 5, only samples collected before dialysis were included. CL could not be estimated for 11 patients in the PK population.
Groups in this outcome
Carfilzomib - Normal RF
Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) \> 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles. If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.
Carfilzomib - Mild RI
Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles. If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.
Carfilzomib - Moderate RI
Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles. If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.
Carfilzomib - Severe RI
Participants with severe renal impairment (CrCL \< 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles. If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.
Carfilzomib - Dialysis
Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles. If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.
| Group | Source count |
|---|---|
| Carfilzomib - Normal RF | 6 |
| Carfilzomib - Mild RI | 6 |
| Carfilzomib - Moderate RI | 3 |
| Carfilzomib - Severe RI | 4 |
| Carfilzomib - Dialysis | 5 |
Reported measurements
Source class 1
| Group | Value | Spread | Lower | Upper | Comment |
|---|---|---|---|---|---|
| Carfilzomib - Normal RF | 151 | 79.3 | Not reported | Not reported | Not reported |
| Carfilzomib - Mild RI | 113 | 40.7 | Not reported | Not reported | Not reported |
| Carfilzomib - Moderate RI | 288 | 264 | Not reported | Not reported | Not reported |
| Carfilzomib - Severe RI | 170 | 58.4 | Not reported | Not reported | Not reported |
| Carfilzomib - Dialysis | 170 | 60.2 | Not reported | Not reported | Not reported |
Source statistical analyses
- ci Lower Limit
- -2.129
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 0.914
- group Description
- In order to estimate a possible effect of renal function, the relationship between the clearance of carfilzomib and creatinine clearance (CrCl) was explored using a mixed-effects model that included CrCl. The slope of the regression of CL as a function of CrCL at Cycle 1, Day 1 was evaluated using a linear regression model that included CrCL as continuous variables (excluding the hemodialysis group).
- group Ids
- OG000
- OG001
- OG002
- OG003
- non Inferiority Type
- SUPERIORITY_OR_OTHER
- p Value
- 0.4114
- param Type
- Slope
- param Value
- -0.607
- statistical Method
- Regression, Linear
Complete source fields
- analyses
- ci Lower Limit
- -2.129
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 95
- ci Upper Limit
- 0.914
- group Description
- In order to estimate a possible effect of renal function, the relationship between the clearance of carfilzomib and creatinine clearance (CrCl) was explored using a mixed-effects model that included CrCl. The slope of the regression of CL as a function of CrCL at Cycle 1, Day 1 was evaluated using a linear regression model that included CrCL as continuous variables (excluding the hemodialysis group).
- group Ids
- OG000
- OG001
- OG002
- OG003
- non Inferiority Type
- SUPERIORITY_OR_OTHER
- p Value
- 0.4114
- param Type
- Slope
- param Value
- -0.607
- statistical Method
- Regression, Linear
- classes
- categories
- measurements
- group Id
- OG000
- spread
- 79.3
- value
- 151
- group Id
- OG001
- spread
- 40.7
- value
- 113
- group Id
- OG002
- spread
- 264
- value
- 288
- group Id
- OG003
- spread
- 58.4
- value
- 170
- group Id
- OG004
- spread
- 60.2
- value
- 170
- denoms
- counts
- group Id
- OG000
- value
- 6
- group Id
- OG001
- value
- 6
- group Id
- OG002
- value
- 3
- group Id
- OG003
- value
- 4
- group Id
- OG004
- value
- 5
- units
- Participants
- description
- Plasma concentrations of carfilzomib was determined by a validated liquid chromatography tandem mass spectrometry (LC MS/MS) method. The lower limit of quantitation (LLOQ) was 0.300 ng/mL. Concentration values that were below the LLOQ (BLQ) were set to zero. Pharmacokinetic (PK) parameters were calculated from the individual plasma concentrations of carfilzomib using a noncompartmental method.
- dispersion Type
- Standard Deviation
- groups
- description
- Participants with normal renal function (RF; defined as 24-hour urine creatinine clearance (CrCL) \> 80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles. If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.
- id
- OG000
- title
- Carfilzomib - Normal RF
- description
- Participants with mild renal impairment (RI; CrCL between 50-80 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles. If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.
- id
- OG001
- title
- Carfilzomib - Mild RI
- description
- Participants with moderate renal impairment (CrCL between 30-49 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles. If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.
- id
- OG002
- title
- Carfilzomib - Moderate RI
- description
- Participants with severe renal impairment (CrCL \< 30 mL/minute) received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles. If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.
- id
- OG003
- title
- Carfilzomib - Severe RI
- description
- Participants undergoing chronic hemodialysis received carfilzomib, 15 mg/m², administered intravenously on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day cycles for a maximum of 12 cycles. If the 15 mg/m² dose was tolerated the dose could be increased to 20 mg/m² starting at Cycle 2. If 20 mg/m² was tolerated, an additional dose escalation to 27 mg/m² was allowed at Cycle 3 or at subsequent cycles.
- id
- OG004
- title
- Carfilzomib - Dialysis
- param Type
- MEAN
- population Description
- The pharmacokinetic (PK) evaluable population includes participants with stable baseline renal function (Arms 1-4) who completed all protocol-specified treatment and PK blood sample collection through Cycle 1, Day 16. In Group 5, only samples collected before dialysis were included. CL could not be estimated for 11 patients in the PK population.
- reporting Status
- POSTED
- time Frame
- Cycle 1, Day 1 before dosing, at the end of the injection, 5, 15, 30, and 60 minutes, and 1.5, 2, 4, 6 and 24 hours postdose.
- title
- Clearance (CL) of Carfilzomib on Day 1 of Cycle 1
- type
- PRIMARY
- unit Of Measure
- liters/hour
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Preserved source evidence · Not medical advice