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NCT01546038 · OUTCOME

AUCtau of Cytarabine and Ara-U in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3

A Study To Evaluate PF-04449913 With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome · Source last updated 2020-03-03

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

Measure
GEOMETRIC_MEAN
Unit
ng*hr/mL
Interval / dispersion
Geometric Coefficient of Variation
Time frame
Pre-dose, 6 and 24 hours post start of cytarabine infusion on Induction Cycle 1/Day 3

What was measured

Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, levels of both cytarabine and Ara-U were reported.

Analysis population: PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.

Groups in this outcome

Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin

Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m\^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m\^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m\^2 administered as a 3-hour IV infusion every 12 hours (2 g/m\^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.

Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin

Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m\^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m\^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m\^2 administered as a 3-hour IV infusion every 12 hours (2 g/m\^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.

Group identifiers and denominators belong to this outcome only. They may differ in another outcome or in safety reporting.

Analysis denominator · Participants

GroupSource count
Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin9
Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin2

Reported measurements

Cytarabine
Values in ng*hr/mL · Interval/dispersion: Geometric Coefficient of Variation
GroupValueSpreadLowerUpperComment
Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin1070211Not reportedNot reportedNot reported
Phase 1B: Glasdegib 200 mg + Cytarabine/DaunorubicinNANANot reportedNot reportedBased on pre-specified criteria, statistical analysis was not performed if fewer than 3 participants have reportable parameter values. Individual AUCtau values are 276 and 879 ng\*hr/mL.
Ara-U
Values in ng*hr/mL · Interval/dispersion: Geometric Coefficient of Variation
GroupValueSpreadLowerUpperComment
Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin2842032Not reportedNot reportedNot reported
Phase 1B: Glasdegib 200 mg + Cytarabine/DaunorubicinNANANot reportedNot reportedBased on pre-specified criteria, statistical analysis was not performed if fewer than 3 participants have reportable parameter values. Individual AUCtau values are 32430 and 45900 ng\*hr/mL.
Complete source fields
classes
  1. categories
    1. measurements
      1. group Id
        OG000
        spread
        211
        value
        1070
      2. comment
        Based on pre-specified criteria, statistical analysis was not performed if fewer than 3 participants have reportable parameter values. Individual AUCtau values are 276 and 879 ng\*hr/mL.
        group Id
        OG001
        spread
        NA
        value
        NA
    title
    Cytarabine
  2. categories
    1. measurements
      1. group Id
        OG000
        spread
        32
        value
        28420
      2. comment
        Based on pre-specified criteria, statistical analysis was not performed if fewer than 3 participants have reportable parameter values. Individual AUCtau values are 32430 and 45900 ng\*hr/mL.
        group Id
        OG001
        spread
        NA
        value
        NA
    title
    Ara-U
denoms
  1. counts
    1. group Id
      OG000
      value
      9
    2. group Id
      OG001
      value
      2
    units
    Participants
description
Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, levels of both cytarabine and Ara-U were reported.
dispersion Type
Geometric Coefficient of Variation
groups
  1. description
    Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m\^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m\^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m\^2 administered as a 3-hour IV infusion every 12 hours (2 g/m\^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
    id
    OG000
    title
    Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin
  2. description
    Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m\^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m\^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m\^2 administered as a 3-hour IV infusion every 12 hours (2 g/m\^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
    id
    OG001
    title
    Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin
param Type
GEOMETRIC_MEAN
population Description
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.
reporting Status
POSTED
time Frame
Pre-dose, 6 and 24 hours post start of cytarabine infusion on Induction Cycle 1/Day 3
title
AUCtau of Cytarabine and Ara-U in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
type
SECONDARY
unit Of Measure
ng*hr/mL

Download exact source JSON → · Snapshot ctgov-results-191f4516d4760045304b24a0

Preserved source evidence · Not medical advice