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NCT01390818 · OUTCOME

Apparent Volume of Distribution of Total Pimasertib During the Terminal Phase Following Oral Administration (Vz/f) of Pimasertib

Trial of MEK Inhibitor and PI3K/mTOR Inhibitor in Subjects With Locally Advanced or Metastatic Solid Tumors · Source last updated 2017-03-07

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

Measure
GEOMETRIC_MEAN
Unit
liter
Interval / dispersion
95% Confidence Interval
Time frame
Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts

What was measured

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. Apparent volume of distribution during the terminal phase, calculated by CL/f/λz. Terminal rate constant (λz). The regression analysis (determination of λz) was to contain as many data points as possible (but excluding Cmax) and had to include concentration data from at least 3 different time points, consistent with the assessment of a straight line (the terminal elimination phase) on the log-transformed scale.Data was not available for 'Pimasertib (MSC1936369B) 60mg Twice Daily' arm as no subjects were considered evaluable because of limited number of samples collected to characterize the terminal phase rate constant needed for the calculation of Vz/f.

Analysis population: The PK analysis set. Here "N" signifies number of subjects evaluable for this outcome measure and "n" signifies the number of subjects evaluable at specific time points.

Groups in this outcome

Pimasertib (MSC1936369B) 15mg

Pimasertib (MSC1936369B) capsule administered at a single oral dose of 15 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).

Pimasertib (MSC1936369B) 30mg

Pimasertib (MSC1936369B) capsule administered at a single oral dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).

Pimasertib (MSC1936369B) 60mg

Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).

Pimasertib (MSC1936369B) 90mg

Pimasertib (MSC1936369B) capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).

Pimasertib (MSC1936369B) 45mg Twice Daily

Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 45 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).

Pimasertib (MSC1936369B) 60mg Twice Daily

Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).

TNBC: Pimasertib 60mg Once Daily

Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).

NSCLC: Pimasertib 60mg Once Daily

Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).

CRC: Pimasertib 60mg Once Daily

Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).

MEL: Pimasertib 60mg Once Daily

Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).

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

Analysis denominator · Participants

GroupSource count
Pimasertib (MSC1936369B) 15mg6
Pimasertib (MSC1936369B) 30mg10
Pimasertib (MSC1936369B) 60mg26
Pimasertib (MSC1936369B) 90mg14
Pimasertib (MSC1936369B) 45mg Twice Daily3
Pimasertib (MSC1936369B) 60mg Twice Daily0
TNBC: Pimasertib 60mg Once Daily26
NSCLC: Pimasertib 60mg Once Daily24
CRC: Pimasertib 60mg Once Daily18
MEL: Pimasertib 60mg Once Daily15

Reported measurements

Day 1 (n=6, 9, 23, 13, 3, 0, 22, 22, 14, 13)
Values in liter · Interval/dispersion: 95% Confidence Interval
GroupValueSpreadLowerUpperComment
Pimasertib (MSC1936369B) 15mg294.3Not reported218.5396.4Not reported
Pimasertib (MSC1936369B) 30mg240.2Not reported202.5284.9Not reported
Pimasertib (MSC1936369B) 60mg282.8Not reported227.7351.4Not reported
Pimasertib (MSC1936369B) 90mg283.0Not reported224.0357.6Not reported
Pimasertib (MSC1936369B) 45mg Twice Daily394.1Not reported146.91058Not reported
TNBC: Pimasertib 60mg Once Daily223.8Not reported182.7274.3Not reported
NSCLC: Pimasertib 60mg Once Daily226.9Not reported193.9265.4Not reported
CRC: Pimasertib 60mg Once Daily216.2Not reported174.6267.8Not reported
MEL: Pimasertib 60mg Once Daily322.0Not reported251.5412.3Not reported
Day 15 (n=6, 9, 13, 9, 0, 0, 16, 16, 9, 12)
Values in liter · Interval/dispersion: 95% Confidence Interval
GroupValueSpreadLowerUpperComment
Pimasertib (MSC1936369B) 15mg188.7Not reported133.4266.9Not reported
Pimasertib (MSC1936369B) 30mg261.8Not reported187.9364.8Not reported
Pimasertib (MSC1936369B) 60mg396.4Not reported276.9567.3Not reported
Pimasertib (MSC1936369B) 90mg302.4Not reported223.1409.7Not reported
Pimasertib (MSC1936369B) 45mg Twice DailyNANot reportedNANAData could not be calculated because there were no subjects evaluated for this arm at the specified time point because of limited number of samples collected to characterize the terminal phase rate constant needed for the calculation of Vz/f.
TNBC: Pimasertib 60mg Once Daily226.3Not reported189.7270.1Not reported
NSCLC: Pimasertib 60mg Once Daily250.9Not reported214.2293.9Not reported
CRC: Pimasertib 60mg Once Daily230.6Not reported169.0314.6Not reported
MEL: Pimasertib 60mg Once Daily273.8Not reported213.8350.7Not reported
Complete source fields
classes
  1. categories
    1. measurements
      1. group Id
        OG000
        lower Limit
        218.5
        upper Limit
        396.4
        value
        294.3
      2. group Id
        OG001
        lower Limit
        202.5
        upper Limit
        284.9
        value
        240.2
      3. group Id
        OG002
        lower Limit
        227.7
        upper Limit
        351.4
        value
        282.8
      4. group Id
        OG003
        lower Limit
        224.0
        upper Limit
        357.6
        value
        283.0
      5. group Id
        OG004
        lower Limit
        146.9
        upper Limit
        1058
        value
        394.1
      6. group Id
        OG006
        lower Limit
        182.7
        upper Limit
        274.3
        value
        223.8
      7. group Id
        OG007
        lower Limit
        193.9
        upper Limit
        265.4
        value
        226.9
      8. group Id
        OG008
        lower Limit
        174.6
        upper Limit
        267.8
        value
        216.2
      9. group Id
        OG009
        lower Limit
        251.5
        upper Limit
        412.3
        value
        322.0
    title
    Day 1 (n=6, 9, 23, 13, 3, 0, 22, 22, 14, 13)
  2. categories
    1. measurements
      1. group Id
        OG000
        lower Limit
        133.4
        upper Limit
        266.9
        value
        188.7
      2. group Id
        OG001
        lower Limit
        187.9
        upper Limit
        364.8
        value
        261.8
      3. group Id
        OG002
        lower Limit
        276.9
        upper Limit
        567.3
        value
        396.4
      4. group Id
        OG003
        lower Limit
        223.1
        upper Limit
        409.7
        value
        302.4
      5. comment
        Data could not be calculated because there were no subjects evaluated for this arm at the specified time point because of limited number of samples collected to characterize the terminal phase rate constant needed for the calculation of Vz/f.
        group Id
        OG004
        lower Limit
        NA
        upper Limit
        NA
        value
        NA
      6. group Id
        OG006
        lower Limit
        189.7
        upper Limit
        270.1
        value
        226.3
      7. group Id
        OG007
        lower Limit
        214.2
        upper Limit
        293.9
        value
        250.9
      8. group Id
        OG008
        lower Limit
        169.0
        upper Limit
        314.6
        value
        230.6
      9. group Id
        OG009
        lower Limit
        213.8
        upper Limit
        350.7
        value
        273.8
    title
    Day 15 (n=6, 9, 13, 9, 0, 0, 16, 16, 9, 12)
denoms
  1. counts
    1. group Id
      OG000
      value
      6
    2. group Id
      OG001
      value
      10
    3. group Id
      OG002
      value
      26
    4. group Id
      OG003
      value
      14
    5. group Id
      OG004
      value
      3
    6. group Id
      OG005
      value
      0
    7. group Id
      OG006
      value
      26
    8. group Id
      OG007
      value
      24
    9. group Id
      OG008
      value
      18
    10. group Id
      OG009
      value
      15
    units
    Participants
description
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. Apparent volume of distribution during the terminal phase, calculated by CL/f/λz. Terminal rate constant (λz). The regression analysis (determination of λz) was to contain as many data points as possible (but excluding Cmax) and had to include concentration data from at least 3 different time points, consistent with the assessment of a straight line (the terminal elimination phase) on the log-transformed scale.Data was not available for 'Pimasertib (MSC1936369B) 60mg Twice Daily' arm as no subjects were considered evaluable because of limited number of samples collected to characterize the terminal phase rate constant needed for the calculation of Vz/f.
dispersion Type
95% Confidence Interval
groups
  1. description
    Pimasertib (MSC1936369B) capsule administered at a single oral dose of 15 milligram (mg) on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
    id
    OG000
    title
    Pimasertib (MSC1936369B) 15mg
  2. description
    Pimasertib (MSC1936369B) capsule administered at a single oral dose of 30 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
    id
    OG001
    title
    Pimasertib (MSC1936369B) 30mg
  3. description
    Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
    id
    OG002
    title
    Pimasertib (MSC1936369B) 60mg
  4. description
    Pimasertib (MSC1936369B) capsule administered at a single oral dose of 90 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
    id
    OG003
    title
    Pimasertib (MSC1936369B) 90mg
  5. description
    Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 45 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
    id
    OG004
    title
    Pimasertib (MSC1936369B) 45mg Twice Daily
  6. description
    Pimasertib (MSC1936369B) capsule administered twice, orally, at a dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DE Cohort).
    id
    OG005
    title
    Pimasertib (MSC1936369B) 60mg Twice Daily
  7. description
    Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
    id
    OG006
    title
    TNBC: Pimasertib 60mg Once Daily
  8. description
    Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
    id
    OG007
    title
    NSCLC: Pimasertib 60mg Once Daily
  9. description
    Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
    id
    OG008
    title
    CRC: Pimasertib 60mg Once Daily
  10. description
    Pimasertib (MSC1936369B) capsule administered at a single oral dose of 60 mg on Day 1 of 21 day cycle until disease progression, intolerable toxicity, Investigator's decision to discontinue treatment, or withdrawal of consent by the subject (DSE Cohort).
    id
    OG009
    title
    MEL: Pimasertib 60mg Once Daily
param Type
GEOMETRIC_MEAN
population Description
The PK analysis set. Here "N" signifies number of subjects evaluable for this outcome measure and "n" signifies the number of subjects evaluable at specific time points.
reporting Status
POSTED
time Frame
Predose 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hour post dose on Day 1, 15 for DSE Cohorts; Predose 0.5, 1, 1.5, 2, 3, 4, 8, 10 and 24 hour post dose on Day 1, 15 for DE cohorts
title
Apparent Volume of Distribution of Total Pimasertib During the Terminal Phase Following Oral Administration (Vz/f) of Pimasertib
type
SECONDARY
unit Of Measure
liter

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Preserved source evidence · Not medical advice