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NCT02211014 · OUTCOME

Bruton Tyrosine Kinase (BTK) Occupancy

An Open-Label, Phase 1b Study of Acalabrutinib With and Without Dexamethasone in Subjects With Multiple Myeloma · Source last updated 2020-07-31

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

Measure
MEAN
Unit
percentage of occupied BTK
Interval / dispersion
Standard Deviation
Time frame
On Days 1 and 8: pre-dose and at 4 hours after the morning dose. On Days 28 and 56: morning pre-dose only.

What was measured

The percent occupied BTK was calculated in each subject's peripheral blood mononuclear cells (PBMC) sample for each assessment timepoint using an ELISA-based method. Samples from 17 subjects met the criteria for data inclusion, having a dynamic range (signal to noise) of ≥5 for the Day 1 pre-dose timepoint. Acalabrutinib administered at 100 mg bid resulted in a median steady-state (Day 8) BTK target occupancy level of 95% and 98% for Cohort 1 and Cohort 2, respectively. The Days 28 and 56 assessments, both taken at pre-dose, were \>97% occupancy for each cohort. Intersubject variability was low, with 6 of 7 (86%) subjects in Cohort 1 and 4 of 5 (80%) subjects in Cohort 2 having \>90% BTK occupancy at steady-state trough (12h post-dose). The single subject in Cohort 2 with \<90% occupancy at Day 8 pre-dose did not take their Day 7 doses.

Analysis population: 17 (of 27) subjects with evaluable data. For 10 subjects the data was excluded due to: no Day 1 sample received, low cells events or parent populations, or other deviation. Day 1 post and additional time points, further decrease of evaluable data due to: subject discontinuation, low cells events or parent populations, or other deviation.

Groups in this outcome

Cohort 1 - Day 1 Pre

Acalabrutinib 100 mg twice daily (bid) continuously

Cohort 2 - Day 1 Pre

Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly

Cohort 1 - Day 1 Post

Acalabrutinib 100 mg twice daily (bid) continuously

Cohort 2 - Day 1 Post

Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly

Cohort 1 - Day 8 Pre

Acalabrutinib 100 mg twice daily (bid) continuously

Cohort 2 - Day 8 Pre

Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly

Cohort 1 - Day 8 Post

Acalabrutinib 100 mg twice daily (bid) continuously

Cohort 2 - Day 8 Post

Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly

Cohort 1 - Day 28 Pre

Acalabrutinib 100 mg twice daily (bid) continuously

Cohort 2 - Day 28 Pre

Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly

Cohort 1 - Day 56 Pre

Acalabrutinib 100 mg twice daily (bid) continuously

Cohort 2 - Day 56 Pre

Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly

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

Analysis denominator · Participants

GroupSource count
Cohort 1 - Day 1 Pre9
Cohort 2 - Day 1 Pre8
Cohort 1 - Day 1 Post8
Cohort 2 - Day 1 Post8
Cohort 1 - Day 8 Pre7
Cohort 2 - Day 8 Pre5
Cohort 1 - Day 8 Post7
Cohort 2 - Day 8 Post6
Cohort 1 - Day 28 Pre7
Cohort 2 - Day 28 Pre6
Cohort 1 - Day 56 Pre5
Cohort 2 - Day 56 Pre4

Reported measurements

Source class 1
Values in percentage of occupied BTK · Interval/dispersion: Standard Deviation
GroupValueSpreadLowerUpperComment
Cohort 1 - Day 1 Pre00Not reportedNot reportedNot reported
Cohort 2 - Day 1 Pre00Not reportedNot reportedNot reported
Cohort 1 - Day 1 Post98.50.9Not reportedNot reportedNot reported
Cohort 2 - Day 1 Post98.51.3Not reportedNot reportedNot reported
Cohort 1 - Day 8 Pre93.26.6Not reportedNot reportedNot reported
Cohort 2 - Day 8 Pre94.38.8Not reportedNot reportedNot reported
Cohort 1 - Day 8 Post98.61.1Not reportedNot reportedNot reported
Cohort 2 - Day 8 Post96.84.8Not reportedNot reportedNot reported
Cohort 1 - Day 28 Pre97.61.8Not reportedNot reportedNot reported
Cohort 2 - Day 28 Pre95.85.5Not reportedNot reportedNot reported
Cohort 1 - Day 56 Pre95.76.2Not reportedNot reportedNot reported
Cohort 2 - Day 56 Pre97.61.3Not reportedNot reportedNot reported
Complete source fields
classes
  1. categories
    1. measurements
      1. group Id
        OG000
        spread
        0
        value
        0
      2. group Id
        OG001
        spread
        0
        value
        0
      3. group Id
        OG002
        spread
        0.9
        value
        98.5
      4. group Id
        OG003
        spread
        1.3
        value
        98.5
      5. group Id
        OG004
        spread
        6.6
        value
        93.2
      6. group Id
        OG005
        spread
        8.8
        value
        94.3
      7. group Id
        OG006
        spread
        1.1
        value
        98.6
      8. group Id
        OG007
        spread
        4.8
        value
        96.8
      9. group Id
        OG008
        spread
        1.8
        value
        97.6
      10. group Id
        OG009
        spread
        5.5
        value
        95.8
      11. group Id
        OG010
        spread
        6.2
        value
        95.7
      12. group Id
        OG011
        spread
        1.3
        value
        97.6
denoms
  1. counts
    1. group Id
      OG000
      value
      9
    2. group Id
      OG001
      value
      8
    3. group Id
      OG002
      value
      8
    4. group Id
      OG003
      value
      8
    5. group Id
      OG004
      value
      7
    6. group Id
      OG005
      value
      5
    7. group Id
      OG006
      value
      7
    8. group Id
      OG007
      value
      6
    9. group Id
      OG008
      value
      7
    10. group Id
      OG009
      value
      6
    11. group Id
      OG010
      value
      5
    12. group Id
      OG011
      value
      4
    units
    Participants
description
The percent occupied BTK was calculated in each subject's peripheral blood mononuclear cells (PBMC) sample for each assessment timepoint using an ELISA-based method. Samples from 17 subjects met the criteria for data inclusion, having a dynamic range (signal to noise) of ≥5 for the Day 1 pre-dose timepoint. Acalabrutinib administered at 100 mg bid resulted in a median steady-state (Day 8) BTK target occupancy level of 95% and 98% for Cohort 1 and Cohort 2, respectively. The Days 28 and 56 assessments, both taken at pre-dose, were \>97% occupancy for each cohort. Intersubject variability was low, with 6 of 7 (86%) subjects in Cohort 1 and 4 of 5 (80%) subjects in Cohort 2 having \>90% BTK occupancy at steady-state trough (12h post-dose). The single subject in Cohort 2 with \<90% occupancy at Day 8 pre-dose did not take their Day 7 doses.
dispersion Type
Standard Deviation
groups
  1. description
    Acalabrutinib 100 mg twice daily (bid) continuously
    id
    OG000
    title
    Cohort 1 - Day 1 Pre
  2. description
    Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly
    id
    OG001
    title
    Cohort 2 - Day 1 Pre
  3. description
    Acalabrutinib 100 mg twice daily (bid) continuously
    id
    OG002
    title
    Cohort 1 - Day 1 Post
  4. description
    Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly
    id
    OG003
    title
    Cohort 2 - Day 1 Post
  5. description
    Acalabrutinib 100 mg twice daily (bid) continuously
    id
    OG004
    title
    Cohort 1 - Day 8 Pre
  6. description
    Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly
    id
    OG005
    title
    Cohort 2 - Day 8 Pre
  7. description
    Acalabrutinib 100 mg twice daily (bid) continuously
    id
    OG006
    title
    Cohort 1 - Day 8 Post
  8. description
    Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly
    id
    OG007
    title
    Cohort 2 - Day 8 Post
  9. description
    Acalabrutinib 100 mg twice daily (bid) continuously
    id
    OG008
    title
    Cohort 1 - Day 28 Pre
  10. description
    Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly
    id
    OG009
    title
    Cohort 2 - Day 28 Pre
  11. description
    Acalabrutinib 100 mg twice daily (bid) continuously
    id
    OG010
    title
    Cohort 1 - Day 56 Pre
  12. description
    Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly
    id
    OG011
    title
    Cohort 2 - Day 56 Pre
param Type
MEAN
population Description
17 (of 27) subjects with evaluable data. For 10 subjects the data was excluded due to: no Day 1 sample received, low cells events or parent populations, or other deviation. Day 1 post and additional time points, further decrease of evaluable data due to: subject discontinuation, low cells events or parent populations, or other deviation.
reporting Status
POSTED
time Frame
On Days 1 and 8: pre-dose and at 4 hours after the morning dose. On Days 28 and 56: morning pre-dose only.
title
Bruton Tyrosine Kinase (BTK) Occupancy
type
SECONDARY
unit Of Measure
percentage of occupied BTK

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Preserved source evidence · Not medical advice