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NCT01713582 · OUTCOME

Apparent Total Body Clearance (CL/F) of MK-8628/OTX015

A Dose-finding Study of the Bromodomain (Brd) Inhibitor OTX015/ Birabresib (MK-8628) in Hematologic Malignancies (MK-8628-001) · Source last updated 2021-01-26

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

Measure
MEAN
Unit
L/hour
Interval / dispersion
Standard Deviation
Time frame
cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position

What was measured

Data were collected in Cycle 1 according to dosing regimen and enrollment position at the following sampling schedules: 1) Complete QD for the first 3 participants per dose level: Pre-infusion and 1, 4, 8, 12, and 24h + 1 sampling at either 10h or 16h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 2) Limited QD for participants 4 and higher: Pre-infusion and 1, 4, 6, and 8h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 3) BID: Pre-infusion and at 20 minutes and 1, 2.25, 3.25. 9, 12, and 24h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level. Blood samples for CL/F were measured using liquid chromatography-tandem mass spectrometry and analyzed using a nonlinear mixed-effects modelling software program Monolix version 4.3.2. Results for each dose level and method of administration included participants from both AL and OHM cohorts and different regimen frequencies.

Analysis population: All participants that received at least 1 dose of study therapy and had evaluable data for endpoint. Results were pooled by dose taken and not by disease or regimen.

Groups in this outcome

10 mg QD Dose Escalation Cohort

Participants received 10 mg MK-8628/OTX015 administered PO, QD, in a fasted state.

20 mg QD Dose Escalation Cohort

Participants received 20 mg MK-8628/OTX015 administered PO, QD, in a fasted state.

40 mg QD Dose Escalation Cohort

Participants received 40 mg MK-8628/OTX015 administered PO, QD, in a fasted state..

20 mg BID Dose Escalation Cohort

Participants received 20 mg MK-8628/OTX015 administered PO, BID, with the first daily dose in a fasted state.

80 mg QD Dose Escalation Cohort

Participants received 80 mg MK-8628/OTX015 administered PO, QD, in a fasted state.

40 mg BID Dose Escalation Cohort

Participants received 40 mg MK-8628/OTX015 administered PO, BID, with the first daily dose in a fasted state.

120 mg QD Dose Escalation Cohort

Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state.

160 mg QD Dose Escalation Cohort

Participants received 160 mg MK-8628/OTX015 administered PO, QD, in a fasted state.

80 mg QD Expansion Cohort

Participants received 80 mg MK-8628/OTX015 administered PO, QD, in a fasted state.

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

Analysis denominator · Participants

GroupSource count
10 mg QD Dose Escalation Cohort8
20 mg QD Dose Escalation Cohort6
40 mg QD Dose Escalation Cohort8
20 mg BID Dose Escalation Cohort3
80 mg QD Dose Escalation Cohort11
40 mg BID Dose Escalation Cohort13
120 mg QD Dose Escalation Cohort31
160 mg QD Dose Escalation Cohort5
80 mg QD Expansion Cohort49

Reported measurements

Source class 1
Values in L/hour · Interval/dispersion: Standard Deviation
GroupValueSpreadLowerUpperComment
10 mg QD Dose Escalation Cohort9.711.73Not reportedNot reportedNot reported
20 mg QD Dose Escalation Cohort7.672.13Not reportedNot reportedNot reported
40 mg QD Dose Escalation Cohort7.761.38Not reportedNot reportedNot reported
20 mg BID Dose Escalation Cohort6.531.88Not reportedNot reportedNot reported
80 mg QD Dose Escalation Cohort7.913.04Not reportedNot reportedNot reported
40 mg BID Dose Escalation Cohort7.492.18Not reportedNot reportedNot reported
120 mg QD Dose Escalation Cohort8.612.22Not reportedNot reportedNot reported
160 mg QD Dose Escalation Cohort12.72.80Not reportedNot reportedNot reported
80 mg QD Expansion Cohort8.872.60Not reportedNot reportedNot reported
Complete source fields
classes
  1. categories
    1. measurements
      1. group Id
        OG000
        spread
        1.73
        value
        9.71
      2. group Id
        OG001
        spread
        2.13
        value
        7.67
      3. group Id
        OG002
        spread
        1.38
        value
        7.76
      4. group Id
        OG003
        spread
        1.88
        value
        6.53
      5. group Id
        OG004
        spread
        3.04
        value
        7.91
      6. group Id
        OG005
        spread
        2.18
        value
        7.49
      7. group Id
        OG006
        spread
        2.22
        value
        8.61
      8. group Id
        OG007
        spread
        2.80
        value
        12.7
      9. group Id
        OG008
        spread
        2.60
        value
        8.87
denoms
  1. counts
    1. group Id
      OG000
      value
      8
    2. group Id
      OG001
      value
      6
    3. group Id
      OG002
      value
      8
    4. group Id
      OG003
      value
      3
    5. group Id
      OG004
      value
      11
    6. group Id
      OG005
      value
      13
    7. group Id
      OG006
      value
      31
    8. group Id
      OG007
      value
      5
    9. group Id
      OG008
      value
      49
    units
    Participants
description
Data were collected in Cycle 1 according to dosing regimen and enrollment position at the following sampling schedules: 1) Complete QD for the first 3 participants per dose level: Pre-infusion and 1, 4, 8, 12, and 24h + 1 sampling at either 10h or 16h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 2) Limited QD for participants 4 and higher: Pre-infusion and 1, 4, 6, and 8h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 3) BID: Pre-infusion and at 20 minutes and 1, 2.25, 3.25. 9, 12, and 24h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level. Blood samples for CL/F were measured using liquid chromatography-tandem mass spectrometry and analyzed using a nonlinear mixed-effects modelling software program Monolix version 4.3.2. Results for each dose level and method of administration included participants from both AL and OHM cohorts and different regimen frequencies.
dispersion Type
Standard Deviation
groups
  1. description
    Participants received 10 mg MK-8628/OTX015 administered PO, QD, in a fasted state.
    id
    OG000
    title
    10 mg QD Dose Escalation Cohort
  2. description
    Participants received 20 mg MK-8628/OTX015 administered PO, QD, in a fasted state.
    id
    OG001
    title
    20 mg QD Dose Escalation Cohort
  3. description
    Participants received 40 mg MK-8628/OTX015 administered PO, QD, in a fasted state..
    id
    OG002
    title
    40 mg QD Dose Escalation Cohort
  4. description
    Participants received 20 mg MK-8628/OTX015 administered PO, BID, with the first daily dose in a fasted state.
    id
    OG003
    title
    20 mg BID Dose Escalation Cohort
  5. description
    Participants received 80 mg MK-8628/OTX015 administered PO, QD, in a fasted state.
    id
    OG004
    title
    80 mg QD Dose Escalation Cohort
  6. description
    Participants received 40 mg MK-8628/OTX015 administered PO, BID, with the first daily dose in a fasted state.
    id
    OG005
    title
    40 mg BID Dose Escalation Cohort
  7. description
    Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state.
    id
    OG006
    title
    120 mg QD Dose Escalation Cohort
  8. description
    Participants received 160 mg MK-8628/OTX015 administered PO, QD, in a fasted state.
    id
    OG007
    title
    160 mg QD Dose Escalation Cohort
  9. description
    Participants received 80 mg MK-8628/OTX015 administered PO, QD, in a fasted state.
    id
    OG008
    title
    80 mg QD Expansion Cohort
param Type
MEAN
population Description
All participants that received at least 1 dose of study therapy and had evaluable data for endpoint. Results were pooled by dose taken and not by disease or regimen.
reporting Status
POSTED
time Frame
cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position
title
Apparent Total Body Clearance (CL/F) of MK-8628/OTX015
type
SECONDARY
unit Of Measure
L/hour

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Preserved source evidence · Not medical advice