TriangleNCT03814005 · OUTCOME
Parts A and B, Vss: Volume of Distribution at Steady-state of Pevonedistat
Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.
- Measure
- GEOMETRIC_MEAN
- Unit
- Liters (L)
- Interval / dispersion
- Geometric Coefficient of Variation
- Time frame
- Part A: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Part B: Cycle 1 Day 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length= 28 days)
Analysis population: PK population included all participants who had sufficient dosing in Part A and Part B Cycle 1, had sufficient concentration-time data to permit reliable estimation of PK parameters, and who had not received any excluded concomitant medications through the completion of Part A. Overall number analyzed is the number of participants available for analyses.
Groups in this outcome
Part A: Control Arm: Pevonedistat 20 mg/m^2
Pevonedistat 20 mg/m\^2, infusion, IV, once, on Day 1 of Part A in participants with normal renal and hepatic function with hematologic malignancies (MDS and AML).
Part A: Renal Arm: Pevonedistat 20 mg/m^2
Pevonedistat 20 mg/m\^2, infusion, IV, once, on Day 1 of Part A in participants with severe renal impairment with hematologic malignancies (MDS and AML).
Part A: Mild Hepatic Arm: Pevonedistat 20 mg/m^2
Pevonedistat 20 mg/m\^2, infusion, IV, once, on Day 1 of Part A in participants with mild hepatic impairment with hematologic malignancies (MDS and AML).
Part B: Control Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2
Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 10 mg/m\^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m\^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles.
Part B: Renal Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2
Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 10 mg/m\^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m\^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles.
Part B: Mild Hepatic Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2
Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 10 mg/m\^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m\^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles.
Part B: Control Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2
Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m\^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m\^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles.
Part B: Renal Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2
Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m\^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m\^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles.
Part B: Mild Hepatic Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2
Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m\^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m\^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles.
Part B: Control Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2
Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m\^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m\^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles.
Part B: Renal Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2
Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m\^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m\^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles.
Part B: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2
Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m\^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m\^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles.
| Group | Source count |
|---|---|
| Part A: Control Arm: Pevonedistat 20 mg/m^2 | 10 |
| Part A: Renal Arm: Pevonedistat 20 mg/m^2 | 4 |
| Part A: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 | 3 |
| Part B: Control Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | 0 |
| Part B: Renal Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | 3 |
| Part B: Mild Hepatic Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | 2 |
| Part B: Control Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | 0 |
| Part B: Renal Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | 1 |
| Part B: Mild Hepatic Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | 0 |
| Part B: Control Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 10 |
| Part B: Renal Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 0 |
| Part B: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 1 |
Reported measurements
Source class 1
| Group | Value | Spread | Lower | Upper | Comment |
|---|---|---|---|---|---|
| Part A: Control Arm: Pevonedistat 20 mg/m^2 | 219.288 | 124.3584 | Not reported | Not reported | Not reported |
| Part A: Renal Arm: Pevonedistat 20 mg/m^2 | 293.614 | 36.3707 | Not reported | Not reported | Not reported |
| Part A: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 | 353.570 | 55.0197 | Not reported | Not reported | Not reported |
| Part B: Renal Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | 351.749 | 23.5066 | Not reported | Not reported | Not reported |
| Part B: Mild Hepatic Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | 729.013 | 3.2642 | Not reported | Not reported | Not reported |
| Part B: Renal Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | 336.922 | NA | Not reported | Not reported | Geometric coefficient of variation was not estimable for 1 participant as the values were below the LLOQ of the bioanalytical assay. |
| Part B: Control Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 370.563 | 44.2326 | Not reported | Not reported | Not reported |
| Part B: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 573.044 | NA | Not reported | Not reported | Geometric coefficient of variation was not estimable for 1 participant as the values were below the LLOQ of the bioanalytical assay. |
Complete source fields
- classes
- categories
- measurements
- group Id
- OG000
- spread
- 124.3584
- value
- 219.288
- group Id
- OG001
- spread
- 36.3707
- value
- 293.614
- group Id
- OG002
- spread
- 55.0197
- value
- 353.570
- group Id
- OG004
- spread
- 23.5066
- value
- 351.749
- group Id
- OG005
- spread
- 3.2642
- value
- 729.013
- comment
- Geometric coefficient of variation was not estimable for 1 participant as the values were below the LLOQ of the bioanalytical assay.
- group Id
- OG007
- spread
- NA
- value
- 336.922
- group Id
- OG009
- spread
- 44.2326
- value
- 370.563
- comment
- Geometric coefficient of variation was not estimable for 1 participant as the values were below the LLOQ of the bioanalytical assay.
- group Id
- OG011
- spread
- NA
- value
- 573.044
- denoms
- counts
- group Id
- OG000
- value
- 10
- group Id
- OG001
- value
- 4
- group Id
- OG002
- value
- 3
- group Id
- OG003
- value
- 0
- group Id
- OG004
- value
- 3
- group Id
- OG005
- value
- 2
- group Id
- OG006
- value
- 0
- group Id
- OG007
- value
- 1
- group Id
- OG008
- value
- 0
- group Id
- OG009
- value
- 10
- group Id
- OG010
- value
- 0
- group Id
- OG011
- value
- 1
- units
- Participants
- dispersion Type
- Geometric Coefficient of Variation
- groups
- description
- Pevonedistat 20 mg/m\^2, infusion, IV, once, on Day 1 of Part A in participants with normal renal and hepatic function with hematologic malignancies (MDS and AML).
- id
- OG000
- title
- Part A: Control Arm: Pevonedistat 20 mg/m^2
- description
- Pevonedistat 20 mg/m\^2, infusion, IV, once, on Day 1 of Part A in participants with severe renal impairment with hematologic malignancies (MDS and AML).
- id
- OG001
- title
- Part A: Renal Arm: Pevonedistat 20 mg/m^2
- description
- Pevonedistat 20 mg/m\^2, infusion, IV, once, on Day 1 of Part A in participants with mild hepatic impairment with hematologic malignancies (MDS and AML).
- id
- OG002
- title
- Part A: Mild Hepatic Arm: Pevonedistat 20 mg/m^2
- description
- Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 10 mg/m\^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m\^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles.
- id
- OG003
- title
- Part B: Control Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2
- description
- Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 10 mg/m\^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m\^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles.
- id
- OG004
- title
- Part B: Renal Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2
- description
- Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 10 mg/m\^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m\^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles.
- id
- OG005
- title
- Part B: Mild Hepatic Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2
- description
- Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m\^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m\^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles.
- id
- OG006
- title
- Part B: Control Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2
- description
- Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m\^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m\^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles.
- id
- OG007
- title
- Part B: Renal Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2
- description
- Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 15 mg/m\^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m\^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles.
- id
- OG008
- title
- Part B: Mild Hepatic Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2
- description
- Participants with normal renal and hepatic function with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m\^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m\^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8 and 9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles.
- id
- OG009
- title
- Part B: Control Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2
- description
- Participants with severe renal impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m\^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m\^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles.
- id
- OG010
- title
- Part B: Renal Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2
- description
- Participants with mild hepatic impairment with hematologic malignancies (MDS and AML) who completed Part A and a 4 to 7 days of washout period received pevonedistat 20 mg/m\^2, infusion, IV, once, on Days 1, 3, and 5 in each 28-day treatment cycle in combination with azacitidine 75 mg/m\^2, injection, SC in Cycle 1 or SC or IV in Cycle 2 and subsequent cycles, once on Day 1 through Day 7 or Day 1 through Day 5, and on Days 8-9 until symptomatic deterioration or PD, discontinuation for any reason, study stopped by the sponsor, or up to 12 cycles.
- id
- OG011
- title
- Part B: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2
- param Type
- GEOMETRIC_MEAN
- population Description
- PK population included all participants who had sufficient dosing in Part A and Part B Cycle 1, had sufficient concentration-time data to permit reliable estimation of PK parameters, and who had not received any excluded concomitant medications through the completion of Part A. Overall number analyzed is the number of participants available for analyses.
- reporting Status
- POSTED
- time Frame
- Part A: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose; Part B: Cycle 1 Day 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length= 28 days)
- title
- Parts A and B, Vss: Volume of Distribution at Steady-state of Pevonedistat
- type
- SECONDARY
- unit Of Measure
- Liters (L)
Download exact source JSON → · Snapshot ctgov-results-25a395029948b04d52b1253f
Preserved source evidence · Not medical advice