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NCT03814005 · OUTCOME

Part B: Cmax: Maximum Observed Plasma Concentration for Pevonedistat Following Multiple Dose

A Study of Pevonedistat in People With Blood Cancers or Solid Tumors With Kidney or Liver Problems · Source last updated 2024-09-05

Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.

Measure
GEOMETRIC_MEAN
Unit
ng/mL
Interval / dispersion
Geometric Coefficient of Variation
Time frame
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 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 identifiers and denominators belong to this outcome only. They may differ in another outcome or in safety reporting.

Analysis denominator · Participants

GroupSource count
Part B: Control Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^20
Part B: Renal Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^23
Part B: Mild Hepatic Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^22
Part B: Control Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^20
Part B: Renal Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^21
Part B: Mild Hepatic Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^20
Part B: Control Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^210
Part B: Renal Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^20
Part B: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^21

Reported measurements

Source class 1
Values in ng/mL · Interval/dispersion: Geometric Coefficient of Variation
GroupValueSpreadLowerUpperComment
Part B: Renal Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^274.7314.941Not reportedNot reportedNot reported
Part B: Mild Hepatic Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^244.7424.579Not reportedNot reportedNot reported
Part B: Renal Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2128.00NANot reportedNot reportedGeometric coefficient of variation was not estimable for 1 participant as the values were below the lower limit of quantitation (LLOQ) of the bioanalytical assay.
Part B: Control Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2141.5537.468Not reportedNot reportedNot reported
Part B: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^275.80NANot reportedNot reportedGeometric coefficient of variation was not estimable for 1 participant as the values were below the LLOQ of the bioanalytical assay.
Complete source fields
classes
  1. categories
    1. measurements
      1. group Id
        OG001
        spread
        14.941
        value
        74.73
      2. group Id
        OG002
        spread
        24.579
        value
        44.74
      3. comment
        Geometric coefficient of variation was not estimable for 1 participant as the values were below the lower limit of quantitation (LLOQ) of the bioanalytical assay.
        group Id
        OG004
        spread
        NA
        value
        128.00
      4. group Id
        OG006
        spread
        37.468
        value
        141.55
      5. comment
        Geometric coefficient of variation was not estimable for 1 participant as the values were below the LLOQ of the bioanalytical assay.
        group Id
        OG008
        spread
        NA
        value
        75.80
denoms
  1. counts
    1. group Id
      OG000
      value
      0
    2. group Id
      OG001
      value
      3
    3. group Id
      OG002
      value
      2
    4. group Id
      OG003
      value
      0
    5. group Id
      OG004
      value
      1
    6. group Id
      OG005
      value
      0
    7. group Id
      OG006
      value
      10
    8. group Id
      OG007
      value
      0
    9. group Id
      OG008
      value
      1
    units
    Participants
dispersion Type
Geometric Coefficient of Variation
groups
  1. 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
    OG000
    title
    Part B: Control Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2
  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
    OG001
    title
    Part B: Renal Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2
  3. 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
    OG002
    title
    Part B: Mild Hepatic Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2
  4. 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
    OG003
    title
    Part B: Control Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2
  5. 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
    OG004
    title
    Part B: Renal Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2
  6. 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
    OG005
    title
    Part B: Mild Hepatic Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2
  7. 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
    OG006
    title
    Part B: Control Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2
  8. 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
    OG007
    title
    Part B: Renal Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2
  9. 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
    OG008
    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
Cycle 1 Day 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length= 28 days)
title
Part B: Cmax: Maximum Observed Plasma Concentration for Pevonedistat Following Multiple Dose
type
SECONDARY
unit Of Measure
ng/mL

Download exact source JSON → · Snapshot ctgov-results-25a395029948b04d52b1253f

Preserved source evidence · Not medical advice