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NCT02124772 · OUTCOME

Significant Covariates Estimated With a PopPK Model

Study to Investigate Safety, Pharmacokinetic (PK), Pharmacodynamic (PD) and Clinical Activity of Trametinib in Subjects With Cancer or Plexiform Neurofibromas and Trametinib in Combination With Dabrafenib in Subjects With Cancers Harboring V600 Mutations · Source last updated 2021-07-14

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

Measure
NUMBER
Unit
no units
Interval / dispersion
Not reported
Time frame
pre dose, 1, 2, 4, 7, 10 and 24 hours post trametinib dose on Cycle 1 Day 15 (part A and B) and pre dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post trametinib dose on Cycle 1 Day 15 (part C and D). The duration of 1 cycle was 28 days.

What was measured

The population pharmacokinetic (PopPK) model of trametinib can be described using a two-compartment model with dual sequential 1st order absorption (Ka1, Ka2) and 1st order elimination. Sex and weight are significant covariates on apparent clearance (CL/F), and weight is also a significant covariate on apparent intercompartmental clearance (Q/F). Use of dabrafenib, yes or no, is a covariate on the relative bioavailability of trametinib, reflecting the effect of dabrafenib on the PK of trametinib. The estimates of these covariates (effect of weight on CL/F, effect of sex on CL/F, effect of weight on Q/F, effect of combination with dabrafenib on relative bioavailability F1) calculated with the PopPK model are summarized in this record.

Analysis population: All subjects who received at least one dose of trametinib in Part A, B, C and D and provided an evaluable PK profile. All trametinib and dabrafenib concentration-time data were combined and included in a population PK analysis that examined the influence of demographics on the PK of study treatment.

Groups in this outcome

Part A, B, C and D - All Participants With PK Data

Participants in the study (all doses and all tumor types) with available pharmacokinetic data

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 A, B, C and D - All Participants With PK Data133

Reported measurements

Effect of weight on CL/F
Values in no units · Interval/dispersion: Not reported
GroupValueSpreadLowerUpperComment
Part A, B, C and D - All Participants With PK Data0.788Not reportedNot reportedNot reportedNot reported
Effect of sex on CL/F
Values in no units · Interval/dispersion: Not reported
GroupValueSpreadLowerUpperComment
Part A, B, C and D - All Participants With PK Data1.24Not reportedNot reportedNot reportedNot reported
Effect of weight on Q/F
Values in no units · Interval/dispersion: Not reported
GroupValueSpreadLowerUpperComment
Part A, B, C and D - All Participants With PK Data0.679Not reportedNot reportedNot reportedNot reported
Effect of combination with dabrafenib on relative bioavailability F1
Values in no units · Interval/dispersion: Not reported
GroupValueSpreadLowerUpperComment
Part A, B, C and D - All Participants With PK Data0.876Not reportedNot reportedNot reportedNot reported
Complete source fields
classes
  1. categories
    1. measurements
      1. group Id
        OG000
        value
        0.788
    title
    Effect of weight on CL/F
  2. categories
    1. measurements
      1. group Id
        OG000
        value
        1.24
    title
    Effect of sex on CL/F
  3. categories
    1. measurements
      1. group Id
        OG000
        value
        0.679
    title
    Effect of weight on Q/F
  4. categories
    1. measurements
      1. group Id
        OG000
        value
        0.876
    title
    Effect of combination with dabrafenib on relative bioavailability F1
denoms
  1. counts
    1. group Id
      OG000
      value
      133
    units
    Participants
description
The population pharmacokinetic (PopPK) model of trametinib can be described using a two-compartment model with dual sequential 1st order absorption (Ka1, Ka2) and 1st order elimination. Sex and weight are significant covariates on apparent clearance (CL/F), and weight is also a significant covariate on apparent intercompartmental clearance (Q/F). Use of dabrafenib, yes or no, is a covariate on the relative bioavailability of trametinib, reflecting the effect of dabrafenib on the PK of trametinib. The estimates of these covariates (effect of weight on CL/F, effect of sex on CL/F, effect of weight on Q/F, effect of combination with dabrafenib on relative bioavailability F1) calculated with the PopPK model are summarized in this record.
groups
  1. description
    Participants in the study (all doses and all tumor types) with available pharmacokinetic data
    id
    OG000
    title
    Part A, B, C and D - All Participants With PK Data
param Type
NUMBER
population Description
All subjects who received at least one dose of trametinib in Part A, B, C and D and provided an evaluable PK profile. All trametinib and dabrafenib concentration-time data were combined and included in a population PK analysis that examined the influence of demographics on the PK of study treatment.
reporting Status
POSTED
time Frame
pre dose, 1, 2, 4, 7, 10 and 24 hours post trametinib dose on Cycle 1 Day 15 (part A and B) and pre dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post trametinib dose on Cycle 1 Day 15 (part C and D). The duration of 1 cycle was 28 days.
title
Significant Covariates Estimated With a PopPK Model
type
SECONDARY
unit Of Measure
no units

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

Preserved source evidence · Independent clinical review pending · Not medical advice