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NCT01072175 · OUTCOME

Part A: Maximum Plasma Concentration (Cmax) of a Single Dose of Dabrafenib Administered Alone and in Combination With Trametnib

Investigate Safety, Pharmacokinetics and Pharmacodynamics of GSK2118436 & GSK1120212 · Source last updated 2019-07-05

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

Measure
GEOMETRIC_MEAN
Unit
Nanograms per milliliter (ng/mL)
Interval / dispersion
95% Confidence Interval
Time frame
Day 15

What was measured

Blood samples for PK analysis of dabrafenib and its the metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) were obtained at pre-dose and at 1, 2, 3, 4, 6, 8, 10, and 24 hours after dabrafenib administration. From the plasma concentration-time curve, the PK parameter Cmax was determined by standard non-compartmental analysis using WinNonlin. Cmax data are reported as geometric least squares means.

Analysis population: Pharmacokinetic (PK) Population: all participants who received at least one dose of either dabrafenib or trametinib and for whom a PK sample was obtained and analyzed

Groups in this outcome

Part A: Dabrafenib 75 mg

Participants received a single dose of dabrafenib 75 mg gelatin capsules alone on Day 1.

Part A: Dabrafenib 75 mg + Trametinib 2 mg

Participants received a single dose of dabrafenib 75 mg gelatin capsules with repeat dose trametinib (Day 15).

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: Dabrafenib 75 mg8
Part A: Dabrafenib 75 mg + Trametinib 2 mg8

Reported measurements

GSK2118436
Values in Nanograms per milliliter (ng/mL) · Interval/dispersion: 95% Confidence Interval
GroupValueSpreadLowerUpperComment
Part A: Dabrafenib 75 mg509Not reported379685Not reported
Part A: Dabrafenib 75 mg + Trametinib 2 mg524Not reported390705Not reported
GSK2285403
Values in Nanograms per milliliter (ng/mL) · Interval/dispersion: 95% Confidence Interval
GroupValueSpreadLowerUpperComment
Part A: Dabrafenib 75 mg259Not reported190352Not reported
Part A: Dabrafenib 75 mg + Trametinib 2 mg255Not reported196331Not reported
GSK2298683
Values in Nanograms per milliliter (ng/mL) · Interval/dispersion: 95% Confidence Interval
GroupValueSpreadLowerUpperComment
Part A: Dabrafenib 75 mg724Not reported595879Not reported
Part A: Dabrafenib 75 mg + Trametinib 2 mg747Not reported587951Not reported
GSK2167542
Values in Nanograms per milliliter (ng/mL) · Interval/dispersion: 95% Confidence Interval
GroupValueSpreadLowerUpperComment
Part A: Dabrafenib 75 mg8.37Not reported4.8214.5Not reported
Part A: Dabrafenib 75 mg + Trametinib 2 mg8.16Not reported5.6811.7Not reported

Source statistical analyses

Group order, estimate direction, methods and comments are retained. No treatment ranking is inferred.

  1. ci Lower Limit
    0.79
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    90
    ci Upper Limit
    1.34
    estimate Comment
    Geometric mean ratio (Day 15 Cmax/Day 1 Cmax) and 90% confidence interval for dabrafenib were calculated.
    group Ids
    1. OG000
    2. OG001
    non Inferiority Comment
    Cmax of dabrafenib was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.
    non Inferiority Type
    NON_INFERIORITY_OR_EQUIVALENCE
    param Type
    Geometric Mean Ratio
    param Value
    1.03
  2. ci Lower Limit
    0.78
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    90
    ci Upper Limit
    1.25
    estimate Comment
    Geometric mean ratio (Day 15 Cmax/Day 1 Cmax) and 90% confidence interval for GSK2285403 were calculated.
    group Ids
    1. OG000
    2. OG001
    non Inferiority Comment
    Cmax of GSK2285403 was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.
    non Inferiority Type
    NON_INFERIORITY_OR_EQUIVALENCE
    param Type
    Geometric Mean Ratio
    param Value
    .99
  3. ci Lower Limit
    0.84
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    90
    ci Upper Limit
    1.27
    estimate Comment
    Geometric mean ratio (Day 15 Cmax/Day 1 Cmax) and 90% confidence interval for GSK2298683 were calculated.
    group Ids
    1. OG000
    2. OG001
    non Inferiority Comment
    Cmax of GSK2298683 was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.
    non Inferiority Type
    NON_INFERIORITY_OR_EQUIVALENCE
    param Type
    Geometric Mean Ratio
    param Value
    1.03
  4. ci Lower Limit
    0.66
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    90
    ci Upper Limit
    1.45
    estimate Comment
    Geometric mean ratio (Day 15 Cmax/Day 1 Cmax) and 90% confidence interval for GSK2167542 were calculated.
    group Ids
    1. OG000
    2. OG001
    non Inferiority Comment
    Cmax of GSK2167542 was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.
    non Inferiority Type
    NON_INFERIORITY_OR_EQUIVALENCE
    param Type
    Geometric Mean Ratio
    param Value
    .98
Complete source fields
analyses
  1. ci Lower Limit
    0.79
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    90
    ci Upper Limit
    1.34
    estimate Comment
    Geometric mean ratio (Day 15 Cmax/Day 1 Cmax) and 90% confidence interval for dabrafenib were calculated.
    group Ids
    1. OG000
    2. OG001
    non Inferiority Comment
    Cmax of dabrafenib was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.
    non Inferiority Type
    NON_INFERIORITY_OR_EQUIVALENCE
    param Type
    Geometric Mean Ratio
    param Value
    1.03
  2. ci Lower Limit
    0.78
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    90
    ci Upper Limit
    1.25
    estimate Comment
    Geometric mean ratio (Day 15 Cmax/Day 1 Cmax) and 90% confidence interval for GSK2285403 were calculated.
    group Ids
    1. OG000
    2. OG001
    non Inferiority Comment
    Cmax of GSK2285403 was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.
    non Inferiority Type
    NON_INFERIORITY_OR_EQUIVALENCE
    param Type
    Geometric Mean Ratio
    param Value
    .99
  3. ci Lower Limit
    0.84
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    90
    ci Upper Limit
    1.27
    estimate Comment
    Geometric mean ratio (Day 15 Cmax/Day 1 Cmax) and 90% confidence interval for GSK2298683 were calculated.
    group Ids
    1. OG000
    2. OG001
    non Inferiority Comment
    Cmax of GSK2298683 was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.
    non Inferiority Type
    NON_INFERIORITY_OR_EQUIVALENCE
    param Type
    Geometric Mean Ratio
    param Value
    1.03
  4. ci Lower Limit
    0.66
    ci Num Sides
    TWO_SIDED
    ci Pct Value
    90
    ci Upper Limit
    1.45
    estimate Comment
    Geometric mean ratio (Day 15 Cmax/Day 1 Cmax) and 90% confidence interval for GSK2167542 were calculated.
    group Ids
    1. OG000
    2. OG001
    non Inferiority Comment
    Cmax of GSK2167542 was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.
    non Inferiority Type
    NON_INFERIORITY_OR_EQUIVALENCE
    param Type
    Geometric Mean Ratio
    param Value
    .98
classes
  1. categories
    1. measurements
      1. group Id
        OG000
        lower Limit
        379
        upper Limit
        685
        value
        509
      2. group Id
        OG001
        lower Limit
        390
        upper Limit
        705
        value
        524
    title
    GSK2118436
  2. categories
    1. measurements
      1. group Id
        OG000
        lower Limit
        190
        upper Limit
        352
        value
        259
      2. group Id
        OG001
        lower Limit
        196
        upper Limit
        331
        value
        255
    title
    GSK2285403
  3. categories
    1. measurements
      1. group Id
        OG000
        lower Limit
        595
        upper Limit
        879
        value
        724
      2. group Id
        OG001
        lower Limit
        587
        upper Limit
        951
        value
        747
    title
    GSK2298683
  4. categories
    1. measurements
      1. group Id
        OG000
        lower Limit
        4.82
        upper Limit
        14.5
        value
        8.37
      2. group Id
        OG001
        lower Limit
        5.68
        upper Limit
        11.7
        value
        8.16
    title
    GSK2167542
denoms
  1. counts
    1. group Id
      OG000
      value
      8
    2. group Id
      OG001
      value
      8
    units
    Participants
description
Blood samples for PK analysis of dabrafenib and its the metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) were obtained at pre-dose and at 1, 2, 3, 4, 6, 8, 10, and 24 hours after dabrafenib administration. From the plasma concentration-time curve, the PK parameter Cmax was determined by standard non-compartmental analysis using WinNonlin. Cmax data are reported as geometric least squares means.
dispersion Type
95% Confidence Interval
groups
  1. description
    Participants received a single dose of dabrafenib 75 mg gelatin capsules alone on Day 1.
    id
    OG000
    title
    Part A: Dabrafenib 75 mg
  2. description
    Participants received a single dose of dabrafenib 75 mg gelatin capsules with repeat dose trametinib (Day 15).
    id
    OG001
    title
    Part A: Dabrafenib 75 mg + Trametinib 2 mg
param Type
GEOMETRIC_MEAN
population Description
Pharmacokinetic (PK) Population: all participants who received at least one dose of either dabrafenib or trametinib and for whom a PK sample was obtained and analyzed
reporting Status
POSTED
time Frame
Day 15
title
Part A: Maximum Plasma Concentration (Cmax) of a Single Dose of Dabrafenib Administered Alone and in Combination With Trametnib
type
PRIMARY
unit Of Measure
Nanograms per milliliter (ng/mL)

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