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NCT01584648 · OUTCOME

Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations

A Study Comparing Trametinib and Dabrafenib Combination Therapy to Dabrafenib Monotherapy in Subjects With BRAF-mutant Melanoma · Source last updated 2021-02-17

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

Measure: MEAN
Unit: Nanogram per Milliliter (ng/mL)
Interval / dispersion: Standard Deviation
Time frame: Week 8 (0, 1-3, 4-6 hours post dose), Weeks 16 and 24 (0 hour pre-dose)

What was measured

Blood samples were collected for PK analysis in all participants. Three blood samples were collected at Week 8: pre-dose, 1-3 hours post dose, and 4-6 hours post dose. One pre-dose blood sample was obtained at Weeks 16 and 24. Plasma concentrations of Dabrafenib (GSK2118436) and its metabolites (Hydroxy-Dabrafenib (GSK2285403), Carboxy-Dabrafenib (GSK2298683), and Desmethyl-Dabrafenib (GSK2167542)) were determined using the currently approved analytical methodology. Only descriptive analysis performed.

Analysis population: PK Population.

Groups in this outcome

Dabrafenib + Trametinib

Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.

Dabrafenib + Placebo

Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Crossover to the combination therapy arm was allowed for subjects still receiving study treatment on the dabrafenib monotherapy arm after the positive result for the final OS analysis.

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

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	203
Dabrafenib + Placebo	194

Reported measurements

GSK2118436, Week 8, pre-dose

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	176
Dabrafenib + Placebo	170

Values in Nanogram per Milliliter (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Dabrafenib + Trametinib	92.1	204.85	Not reported	Not reported	Not reported
Dabrafenib + Placebo	64.4	96.98	Not reported	Not reported	Not reported

GSK2118436, Week 8, 1-3 hours

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	176
Dabrafenib + Placebo	176

Values in Nanogram per Milliliter (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Dabrafenib + Trametinib	1309.6	982.25	Not reported	Not reported	Not reported
Dabrafenib + Placebo	1362.3	992.97	Not reported	Not reported	Not reported

GSK2118436, Week 8, 4-6 hours

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	173
Dabrafenib + Placebo	171

Values in Nanogram per Milliliter (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Dabrafenib + Trametinib	458.9	318.59	Not reported	Not reported	Not reported
Dabrafenib + Placebo	539.7	553.09	Not reported	Not reported	Not reported

GSK2118436, Week 16 pre-dose

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	179
Dabrafenib + Placebo	162

Values in Nanogram per Milliliter (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Dabrafenib + Trametinib	151.6	261.31	Not reported	Not reported	Not reported
Dabrafenib + Placebo	151.02	381.32	Not reported	Not reported	Not reported

GSK2118436, Week 24 pre-dose

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	157
Dabrafenib + Placebo	130

Values in Nanogram per Milliliter (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Dabrafenib + Trametinib	167.0	346.97	Not reported	Not reported	Not reported
Dabrafenib + Placebo	156.5	357.50	Not reported	Not reported	Not reported

GSK2285403, Week 8, pre-dose

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	176
Dabrafenib + Placebo	170

Values in Nanogram per Milliliter (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Dabrafenib + Trametinib	346.6	261.73	Not reported	Not reported	Not reported
Dabrafenib + Placebo	308.9	224.56	Not reported	Not reported	Not reported

GSK2285403, Week 8, 1-3 hours

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	176
Dabrafenib + Placebo	176

Values in Nanogram per Milliliter (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Dabrafenib + Trametinib	361.7	245.92	Not reported	Not reported	Not reported
Dabrafenib + Placebo	341.8	240.96	Not reported	Not reported	Not reported

GSK2285403, Week 8, 4-6 hours

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	174
Dabrafenib + Placebo	171

Values in Nanogram per Milliliter (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Dabrafenib + Trametinib	316.9	208.51	Not reported	Not reported	Not reported
Dabrafenib + Placebo	328.1	234.95	Not reported	Not reported	Not reported

GSK2285403, Week 16 pre-dose

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	179
Dabrafenib + Placebo	162

Values in Nanogram per Milliliter (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Dabrafenib + Trametinib	335.0	228.26	Not reported	Not reported	Not reported
Dabrafenib + Placebo	331.0	250.04	Not reported	Not reported	Not reported

GSK2285403, Week 24 pre-dose

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	157
Dabrafenib + Placebo	130

Values in Nanogram per Milliliter (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Dabrafenib + Trametinib	306.2	203.77	Not reported	Not reported	Not reported
Dabrafenib + Placebo	312.8	250.28	Not reported	Not reported	Not reported

GSK2298683, Week 8, pre-dose

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	176
Dabrafenib + Placebo	172

Values in Nanogram per Milliliter (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Dabrafenib + Trametinib	82.0	123.93	Not reported	Not reported	Not reported
Dabrafenib + Placebo	76.7	109.09	Not reported	Not reported	Not reported

GSK2298683,Week 8, 1-3 hours

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	177
Dabrafenib + Placebo	179

Values in Nanogram per Milliliter (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Dabrafenib + Trametinib	648.5	459.01	Not reported	Not reported	Not reported
Dabrafenib + Placebo	672.7	519.45	Not reported	Not reported	Not reported

GSK2298683, Week 8, 4-6 hours

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	174
Dabrafenib + Placebo	173

Values in Nanogram per Milliliter (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Dabrafenib + Trametinib	391.3	206.70	Not reported	Not reported	Not reported
Dabrafenib + Placebo	502.2	356.72	Not reported	Not reported	Not reported

GSK2298683, Week 16 pre-dose

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	179
Dabrafenib + Placebo	163

Values in Nanogram per Milliliter (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Dabrafenib + Trametinib	128.7	174.26	Not reported	Not reported	Not reported
Dabrafenib + Placebo	121.1	195.15	Not reported	Not reported	Not reported

GSK2298683,Week 24 pre-dose

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	156
Dabrafenib + Placebo	130

Values in Nanogram per Milliliter (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Dabrafenib + Trametinib	126.1	219.82	Not reported	Not reported	Not reported
Dabrafenib + Placebo	145.7	265.57	Not reported	Not reported	Not reported

GSK2167542, Week 8, pre-dose

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	176
Dabrafenib + Placebo	170

Values in Nanogram per Milliliter (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Dabrafenib + Trametinib	3237.2	1694.66	Not reported	Not reported	Not reported
Dabrafenib + Placebo	3469.4	1854.02	Not reported	Not reported	Not reported

GSK2167542, Week 8, 1-3 hours

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	176
Dabrafenib + Placebo	176

Values in Nanogram per Milliliter (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Dabrafenib + Trametinib	4286.3	2514.50	Not reported	Not reported	Not reported
Dabrafenib + Placebo	4456.6	2687.32	Not reported	Not reported	Not reported

GSK2167542, Week 8, 4-6 hours

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	174
Dabrafenib + Placebo	171

Values in Nanogram per Milliliter (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Dabrafenib + Trametinib	6238.3	2716.05	Not reported	Not reported	Not reported
Dabrafenib + Placebo	6891.6	2739.07	Not reported	Not reported	Not reported

GSK2167542, Week 16 pre-dose

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	179
Dabrafenib + Placebo	162

Values in Nanogram per Milliliter (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Dabrafenib + Trametinib	3842.4	2428.74	Not reported	Not reported	Not reported
Dabrafenib + Placebo	4114.1	2432.72	Not reported	Not reported	Not reported

GSK2167542, Week 24 pre-dose

Analysis denominator · Participants

Group	Source count
Dabrafenib + Trametinib	157
Dabrafenib + Placebo	130

Values in Nanogram per Milliliter (ng/mL) · Interval/dispersion: Standard Deviation
Group	Value	Spread	Lower	Upper	Comment
Dabrafenib + Trametinib	3617.9	2645.51	Not reported	Not reported	Not reported
Dabrafenib + Placebo	4193.2	2730.78	Not reported	Not reported	Not reported

Complete source fields

classes

categories
measurements
group Id
OG000
spread
204.85
value
92.1
group Id
OG001
spread
96.98
value
64.4
denoms
counts
group Id
OG000
value
176
group Id
OG001
value
170
units
Participants
title
GSK2118436, Week 8, pre-dose
categories
measurements
group Id
OG000
spread
982.25
value
1309.6
group Id
OG001
spread
992.97
value
1362.3
denoms
counts
group Id
OG000
value
176
group Id
OG001
value
176
units
Participants
title
GSK2118436, Week 8, 1-3 hours
categories
measurements
group Id
OG000
spread
318.59
value
458.9
group Id
OG001
spread
553.09
value
539.7
denoms
counts
group Id
OG000
value
173
group Id
OG001
value
171
units
Participants
title
GSK2118436, Week 8, 4-6 hours
categories
measurements
group Id
OG000
spread
261.31
value
151.6
group Id
OG001
spread
381.32
value
151.02
denoms
counts
group Id
OG000
value
179
group Id
OG001
value
162
units
Participants
title
GSK2118436, Week 16 pre-dose
categories
measurements
group Id
OG000
spread
346.97
value
167.0
group Id
OG001
spread
357.50
value
156.5
denoms
counts
group Id
OG000
value
157
group Id
OG001
value
130
units
Participants
title
GSK2118436, Week 24 pre-dose
categories
measurements
group Id
OG000
spread
261.73
value
346.6
group Id
OG001
spread
224.56
value
308.9
denoms
counts
group Id
OG000
value
176
group Id
OG001
value
170
units
Participants
title
GSK2285403, Week 8, pre-dose
categories
measurements
group Id
OG000
spread
245.92
value
361.7
group Id
OG001
spread
240.96
value
341.8
denoms
counts
group Id
OG000
value
176
group Id
OG001
value
176
units
Participants
title
GSK2285403, Week 8, 1-3 hours
categories
measurements
group Id
OG000
spread
208.51
value
316.9
group Id
OG001
spread
234.95
value
328.1
denoms
counts
group Id
OG000
value
174
group Id
OG001
value
171
units
Participants
title
GSK2285403, Week 8, 4-6 hours
categories
measurements
group Id
OG000
spread
228.26
value
335.0
group Id
OG001
spread
250.04
value
331.0
denoms
counts
group Id
OG000
value
179
group Id
OG001
value
162
units
Participants
title
GSK2285403, Week 16 pre-dose
categories
measurements
group Id
OG000
spread
203.77
value
306.2
group Id
OG001
spread
250.28
value
312.8
denoms
counts
group Id
OG000
value
157
group Id
OG001
value
130
units
Participants
title
GSK2285403, Week 24 pre-dose
categories
measurements
group Id
OG000
spread
123.93
value
82.0
group Id
OG001
spread
109.09
value
76.7
denoms
counts
group Id
OG000
value
176
group Id
OG001
value
172
units
Participants
title
GSK2298683, Week 8, pre-dose
categories
measurements
group Id
OG000
spread
459.01
value
648.5
group Id
OG001
spread
519.45
value
672.7
denoms
counts
group Id
OG000
value
177
group Id
OG001
value
179
units
Participants
title
GSK2298683,Week 8, 1-3 hours

denoms

counts
group Id
OG000
value
203
group Id
OG001
value
194
units
Participants

description

Blood samples were collected for PK analysis in all participants. Three blood samples were collected at Week 8: pre-dose, 1-3 hours post dose, and 4-6 hours post dose. One pre-dose blood sample was obtained at Weeks 16 and 24. Plasma concentrations of Dabrafenib (GSK2118436) and its metabolites (Hydroxy-Dabrafenib (GSK2285403), Carboxy-Dabrafenib (GSK2298683), and Desmethyl-Dabrafenib (GSK2167542)) were determined using the currently approved analytical methodology. Only descriptive analysis performed.

dispersion Type

Standard Deviation

groups

description
Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.
id
OG000
title
Dabrafenib + Trametinib
description
Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Crossover to the combination therapy arm was allowed for subjects still receiving study treatment on the dabrafenib monotherapy arm after the positive result for the final OS analysis.
id
OG001
title
Dabrafenib + Placebo

param Type

MEAN

population Description

PK Population.

reporting Status

POSTED

time Frame

Week 8 (0, 1-3, 4-6 hours post dose), Weeks 16 and 24 (0 hour pre-dose)

title

Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations

type

SECONDARY

unit Of Measure

Nanogram per Milliliter (ng/mL)

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

Preserved source evidence · Not medical advice