NCT01072175 · OUTCOME
Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib
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
- MEDIAN
- Unit
- Hours
- Interval / dispersion
- Full Range
- Time frame
- Day 15 and Day 21
What was measured
The tmax is defined as the time of occurenceof Cmax. Tha tmax was assessed for plasma dabrafenib (DAB) following repeat dosing of dabrafenib 75 and 150 mg BID administered in combination with trametinib. Blood samples for PK analysis of the metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) of dabrafenib were obtained at Day 15 pre-dose and Day 21 pre-dose and at 1, 2, 4, 6, and 8 hours post-dose administration.
Analysis population: PK Population. Only those participants who were available at the indicated time points were analyzed.
Groups in this outcome
Part B: Dabrafenib 75 mg + Trametinib 1 mg
Melanoma BRAF-positive participants who did not receive prior treatment with BRAF inhibitors received dabrafenib 75 mg gelatin capsules BID and trametinib 1 mg tablets QD as continuous daily dosing. Dose escalation decisions were made based on all available pharmacokinetic (PK), safety, and other data from the first 4 evaluable participants, and additional participants were enrolled based on dose-limiting toxicities (DLTs) occurring during the first 3 weeks of treatment.
Part B: Dabrafenib 150 mg + Trametinib 1 mg
Melanoma BRAF-positive participants who did not receive prior treatment with BRAF inhibitors and participants who had salivary ductal cancer received dabrafenib 150 mg gelatin capsules BID and trametinib 1 mg tablets QD as continuous daily dosing. Dose escalation decisions were made based on all available PK, safety, and other data from the first 4 evaluable participants and additional participants were enrolled based on DLTs occurring during the first 3 weeks of treatment.
Part B: Dabrafenib 150 mg + Trametinib 1.5 mg
Melanoma BRAF-positive participants who did not receive prior treatment with BRAF inhibitors received dabrafenib 150 mg gelatin capsules BID and trametinib 1.5 mg tablets QD as continuous daily dosing. Dose escalation decisions were made based on all available PK, safety, and other data from the first 4 evaluable participants, and additional participants were enrolled based on DLTs occurring during the first 3 weeks of treatment.
Part B: Dabrafenib 150 mg + Trametinib 2 mg
Melanoma BRAF-positive participants who received prior treatment with BRAF inhibitors and participants who had colorectal cancer and BRAFi naïve melanoma received dabrafenib 150 mg gelatin capsules BID and trametinib 2 mg tablets QD as continuous daily dosing. Dose escalation did not proceed beyond these doses of dabrafenib and trametinib.
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 |
|---|
| Part B: Dabrafenib 75 mg + Trametinib 1 mg | 6 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1 mg | 8 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | 12 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | 8 |
|---|
Reported measurements
DAB Day 15
Analysis denominator · Participants
| Group | Source count |
|---|
| Part B: Dabrafenib 75 mg + Trametinib 1 mg | 6 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1 mg | 8 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | 12 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | 8 |
|---|
Values in Hours · Interval/dispersion: Full Range| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Part B: Dabrafenib 75 mg + Trametinib 1 mg | 2.00 | Not reported | 1.03 | 2.00 | Not reported |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1 mg | 2.00 | Not reported | 1.03 | 6.00 | Not reported |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | 2.00 | Not reported | 1.00 | 2.10 | Not reported |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | 1.50 | Not reported | 1.00 | 2.00 | Not reported |
|---|
DAB Day 21
Analysis denominator · Participants
| Group | Source count |
|---|
| Part B: Dabrafenib 75 mg + Trametinib 1 mg | 0 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1 mg | 8 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | 12 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | 8 |
|---|
Values in Hours · Interval/dispersion: Full Range| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1 mg | 1.54 | Not reported | 1.00 | 2.00 | Not reported |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | 1.53 | Not reported | 1.00 | 2.03 | Not reported |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | 2.04 | Not reported | 1.00 | 4.03 | Not reported |
|---|
GSK2285403 Day 15
Analysis denominator · Participants
| Group | Source count |
|---|
| Part B: Dabrafenib 75 mg + Trametinib 1 mg | 6 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1 mg | 8 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | 12 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | 8 |
|---|
Values in Hours · Interval/dispersion: Full Range| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Part B: Dabrafenib 75 mg + Trametinib 1 mg | 2.00 | Not reported | 2.00 | 2.03 | Not reported |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1 mg | 2.00 | Not reported | 1.03 | 8.00 | Not reported |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | 2.00 | Not reported | 2.00 | 4.03 | Not reported |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | 2.00 | Not reported | 2.00 | 2.00 | Not reported |
|---|
GSK2285403 Day 21
Analysis denominator · Participants
| Group | Source count |
|---|
| Part B: Dabrafenib 75 mg + Trametinib 1 mg | 0 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1 mg | 8 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | 12 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | 8 |
|---|
Values in Hours · Interval/dispersion: Full Range| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1 mg | 1.97 | Not reported | 0.00 | 2.00 | Not reported |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | 2.00 | Not reported | 1.00 | 2.03 | Not reported |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | 2.07 | Not reported | 1.00 | 6.00 | Not reported |
|---|
GSK2298683 Day 15
Analysis denominator · Participants
| Group | Source count |
|---|
| Part B: Dabrafenib 75 mg + Trametinib 1 mg | 6 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1 mg | 8 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | 12 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | 8 |
|---|
Values in Hours · Interval/dispersion: Full Range| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Part B: Dabrafenib 75 mg + Trametinib 1 mg | 6.00 | Not reported | 4.00 | 8.00 | Not reported |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1 mg | 4.96 | Not reported | 0.00 | 6.30 | Not reported |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | 4.17 | Not reported | 1.00 | 8.02 | Not reported |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | 4.10 | Not reported | 4.00 | 8.00 | Not reported |
|---|
GSK2298683 Day 21
Analysis denominator · Participants
| Group | Source count |
|---|
| Part B: Dabrafenib 75 mg + Trametinib 1 mg | 0 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1 mg | 8 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | 12 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | 8 |
|---|
Values in Hours · Interval/dispersion: Full Range| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1 mg | 4.00 | Not reported | 1.00 | 6.00 | Not reported |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | 4.00 | Not reported | 1.00 | 6.00 | Not reported |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | 4.02 | Not reported | 2.00 | 8.07 | Not reported |
|---|
GSK2167542 Day 15
Analysis denominator · Participants
| Group | Source count |
|---|
| Part B: Dabrafenib 75 mg + Trametinib 1 mg | 6 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1 mg | 8 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | 12 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | 8 |
|---|
Values in Hours · Interval/dispersion: Full Range| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Part B: Dabrafenib 75 mg + Trametinib 1 mg | 0.00 | Not reported | 0.00 | 4.17 | Not reported |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1 mg | 2.94 | Not reported | 0.00 | 8.00 | Not reported |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | 4.17 | Not reported | 1.00 | 8.02 | Not reported |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | 1.52 | Not reported | 0.00 | 2.00 | Not reported |
|---|
GSK2167542 Day 21
Analysis denominator · Participants
| Group | Source count |
|---|
| Part B: Dabrafenib 75 mg + Trametinib 1 mg | 0 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1 mg | 8 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | 12 |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | 8 |
|---|
Values in Hours · Interval/dispersion: Full Range| Group | Value | Spread | Lower | Upper | Comment |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1 mg | 2.00 | Not reported | 1.00 | 2.32 | Not reported |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 1.5 mg | 1.01 | Not reported | 0.00 | 8.00 | Not reported |
|---|
| Part B: Dabrafenib 150 mg + Trametinib 2 mg | 1.50 | Not reported | 0.00 | 8.15 | Not reported |
|---|
Complete source fields
- classes
- categories
- measurements
- group Id
- OG000
- lower Limit
- 1.03
- upper Limit
- 2.00
- value
- 2.00
- group Id
- OG001
- lower Limit
- 1.03
- upper Limit
- 6.00
- value
- 2.00
- group Id
- OG002
- lower Limit
- 1.00
- upper Limit
- 2.10
- value
- 2.00
- group Id
- OG003
- lower Limit
- 1.00
- upper Limit
- 2.00
- value
- 1.50
- denoms
- counts
- group Id
- OG000
- value
- 6
- group Id
- OG001
- value
- 8
- group Id
- OG002
- value
- 12
- group Id
- OG003
- value
- 8
- units
- Participants
- title
- DAB Day 15
- categories
- measurements
- group Id
- OG001
- lower Limit
- 1.00
- upper Limit
- 2.00
- value
- 1.54
- group Id
- OG002
- lower Limit
- 1.00
- upper Limit
- 2.03
- value
- 1.53
- group Id
- OG003
- lower Limit
- 1.00
- upper Limit
- 4.03
- value
- 2.04
- denoms
- counts
- group Id
- OG000
- value
- 0
- group Id
- OG001
- value
- 8
- group Id
- OG002
- value
- 12
- group Id
- OG003
- value
- 8
- units
- Participants
- title
- DAB Day 21
- categories
- measurements
- group Id
- OG000
- lower Limit
- 2.00
- upper Limit
- 2.03
- value
- 2.00
- group Id
- OG001
- lower Limit
- 1.03
- upper Limit
- 8.00
- value
- 2.00
- group Id
- OG002
- lower Limit
- 2.00
- upper Limit
- 4.03
- value
- 2.00
- group Id
- OG003
- lower Limit
- 2.00
- upper Limit
- 2.00
- value
- 2.00
- denoms
- counts
- group Id
- OG000
- value
- 6
- group Id
- OG001
- value
- 8
- group Id
- OG002
- value
- 12
- group Id
- OG003
- value
- 8
- units
- Participants
- title
- GSK2285403 Day 15
- categories
- measurements
- group Id
- OG001
- lower Limit
- 0.00
- upper Limit
- 2.00
- value
- 1.97
- group Id
- OG002
- lower Limit
- 1.00
- upper Limit
- 2.03
- value
- 2.00
- group Id
- OG003
- lower Limit
- 1.00
- upper Limit
- 6.00
- value
- 2.07
- denoms
- counts
- group Id
- OG000
- value
- 0
- group Id
- OG001
- value
- 8
- group Id
- OG002
- value
- 12
- group Id
- OG003
- value
- 8
- units
- Participants
- title
- GSK2285403 Day 21
- categories
- measurements
- group Id
- OG000
- lower Limit
- 4.00
- upper Limit
- 8.00
- value
- 6.00
- group Id
- OG001
- lower Limit
- 0.00
- upper Limit
- 6.30
- value
- 4.96
- group Id
- OG002
- lower Limit
- 1.00
- upper Limit
- 8.02
- value
- 4.17
- group Id
- OG003
- lower Limit
- 4.00
- upper Limit
- 8.00
- value
- 4.10
- denoms
- counts
- group Id
- OG000
- value
- 6
- group Id
- OG001
- value
- 8
- group Id
- OG002
- value
- 12
- group Id
- OG003
- value
- 8
- units
- Participants
- title
- GSK2298683 Day 15
- categories
- measurements
- group Id
- OG001
- lower Limit
- 1.00
- upper Limit
- 6.00
- value
- 4.00
- group Id
- OG002
- lower Limit
- 1.00
- upper Limit
- 6.00
- value
- 4.00
- group Id
- OG003
- lower Limit
- 2.00
- upper Limit
- 8.07
- value
- 4.02
- denoms
- counts
- group Id
- OG000
- value
- 0
- group Id
- OG001
- value
- 8
- group Id
- OG002
- value
- 12
- group Id
- OG003
- value
- 8
- units
- Participants
- title
- GSK2298683 Day 21
- categories
- measurements
- group Id
- OG000
- lower Limit
- 0.00
- upper Limit
- 4.17
- value
- 0.00
- group Id
- OG001
- lower Limit
- 0.00
- upper Limit
- 8.00
- value
- 2.94
- group Id
- OG002
- lower Limit
- 1.00
- upper Limit
- 8.02
- value
- 4.17
- group Id
- OG003
- lower Limit
- 0.00
- upper Limit
- 2.00
- value
- 1.52
- denoms
- counts
- group Id
- OG000
- value
- 6
- group Id
- OG001
- value
- 8
- group Id
- OG002
- value
- 12
- group Id
- OG003
- value
- 8
- units
- Participants
- title
- GSK2167542 Day 15
- categories
- measurements
- group Id
- OG001
- lower Limit
- 1.00
- upper Limit
- 2.32
- value
- 2.00
- group Id
- OG002
- lower Limit
- 0.00
- upper Limit
- 8.00
- value
- 1.01
- group Id
- OG003
- lower Limit
- 0.00
- upper Limit
- 8.15
- value
- 1.50
- denoms
- counts
- group Id
- OG000
- value
- 0
- group Id
- OG001
- value
- 8
- group Id
- OG002
- value
- 12
- group Id
- OG003
- value
- 8
- units
- Participants
- title
- GSK2167542 Day 21
- denoms
- counts
- group Id
- OG000
- value
- 6
- group Id
- OG001
- value
- 8
- group Id
- OG002
- value
- 12
- group Id
- OG003
- value
- 8
- units
- Participants
- description
- The tmax is defined as the time of occurenceof Cmax. Tha tmax was assessed for plasma dabrafenib (DAB) following repeat dosing of dabrafenib 75 and 150 mg BID administered in combination with trametinib. Blood samples for PK analysis of the metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) of dabrafenib were obtained at Day 15 pre-dose and Day 21 pre-dose and at 1, 2, 4, 6, and 8 hours post-dose administration.
- dispersion Type
- Full Range
- groups
- description
- Melanoma BRAF-positive participants who did not receive prior treatment with BRAF inhibitors received dabrafenib 75 mg gelatin capsules BID and trametinib 1 mg tablets QD as continuous daily dosing. Dose escalation decisions were made based on all available pharmacokinetic (PK), safety, and other data from the first 4 evaluable participants, and additional participants were enrolled based on dose-limiting toxicities (DLTs) occurring during the first 3 weeks of treatment.
- id
- OG000
- title
- Part B: Dabrafenib 75 mg + Trametinib 1 mg
- description
- Melanoma BRAF-positive participants who did not receive prior treatment with BRAF inhibitors and participants who had salivary ductal cancer received dabrafenib 150 mg gelatin capsules BID and trametinib 1 mg tablets QD as continuous daily dosing. Dose escalation decisions were made based on all available PK, safety, and other data from the first 4 evaluable participants and additional participants were enrolled based on DLTs occurring during the first 3 weeks of treatment.
- id
- OG001
- title
- Part B: Dabrafenib 150 mg + Trametinib 1 mg
- description
- Melanoma BRAF-positive participants who did not receive prior treatment with BRAF inhibitors received dabrafenib 150 mg gelatin capsules BID and trametinib 1.5 mg tablets QD as continuous daily dosing. Dose escalation decisions were made based on all available PK, safety, and other data from the first 4 evaluable participants, and additional participants were enrolled based on DLTs occurring during the first 3 weeks of treatment.
- id
- OG002
- title
- Part B: Dabrafenib 150 mg + Trametinib 1.5 mg
- description
- Melanoma BRAF-positive participants who received prior treatment with BRAF inhibitors and participants who had colorectal cancer and BRAFi naïve melanoma received dabrafenib 150 mg gelatin capsules BID and trametinib 2 mg tablets QD as continuous daily dosing. Dose escalation did not proceed beyond these doses of dabrafenib and trametinib.
- id
- OG003
- title
- Part B: Dabrafenib 150 mg + Trametinib 2 mg
- param Type
- MEDIAN
- population Description
- PK Population. Only those participants who were available at the indicated time points were analyzed.
- reporting Status
- POSTED
- time Frame
- Day 15 and Day 21
- title
- Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib
- type
- SECONDARY
- unit Of Measure
- Hours
Download exact source JSON → · Snapshot ctgov-results-191f4516d4760045304b24a0
Preserved source evidence · Independent clinical review pending · Not medical advice
Triangle