TriangleNCT02124772 · OUTCOME
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau at Steady-state (AUCtau) of Trametinib When Administered Alone and in Combination With Dabrafenib
Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.
- Measure
- GEOMETRIC_MEAN
- Unit
- hours*ng/mL
- Interval / dispersion
- Geometric Coefficient of Variation
- 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
Pharmacokinetic (PK) parameters were calculated based on trametinib plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for area under the curve calculation. The duration of the dosing interval (tau) was 24 hours for trametinib.
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 with a value for the outcome measure
Groups in this outcome
Part A - TMT 0.0125 mg/kg/Day
Participants treated with trametinib 0.0125 mg/kg/day
Part A - TMT 0.025 mg/kg/Day
Participants treated with trametinib 0.025 mg/kg/day
Part A - TMT 0.032 mg/kg/Day
Participants under 6 years of age treated with trametinib 0.032 mg/kg/day
Part A - TMT 0.04 mg/kg/Day
Participants treated with trametinib 0.04 mg/kg/day
Part B - Neuroblastoma
Participants with refractory or relapsed neuroblastoma treated with trametinib 0.025 mg/kg/day
Part B - LGG Fusion
Participants with recurrent or unresectable low grade glioma (LGG) with BRAF tandem duplication with fusion treated with trametinib 0.025 mg/kg/day
Part B - NF-1 With PN
Participants with neurofibromatosis Type -1 associated plexiform neurofibromas (NF-1 with PN) treated with trametinib 0.025 mg/kg/day
Part B - BRAF V600 Mutant Solid Tumor
Participants with BRAF V600 mutant solid tumors treated with trametinib 0.025 mg/kg/day
Part B - All Tumor Types TMT 0.025 mg/kg/Day
Participants (all tumor types in Part B) treated with trametinib 0.025 mg/kg/day
Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D
Participants treated with a combination therapy of trametinib (0.025 mg/kg/day) plus 50% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (2.63 mg/kg/day for \<12 years old subjects and 2.25 mg/kg/day for ≥12 years old subjects)
Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D
Participants treated with a combination therapy of trametinib (0.025 mg/kg/day) plus 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day for \<12 years old subjects and 4.5 mg/kg/day for ≥12 years old subjects)
Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D
Participants under 6 years of age treated with a combination therapy of trametinib (0.032 mg/kg/day) with 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day)
Part D - LGG
Participants with low grade glioma (LGG) treated with a combination therapy of trametinib (0.032 mg/kg/day for \< 6 years old subjects and 0.025 mg/kg/day for ≥ 6 years old subjects) plus 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day for \<12 years old subjects and 4.5 mg/kg/day for ≥12 years old subjects)
Part D - LCH
Participants with Langerhans cell histiocytosis (LCH) treated with a combination therapy of trametinib (0.032 mg/kg/day for \< 6 years old subjects and 0.025 mg/kg/day for ≥ 6 years old subjects) plus 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day for \<12 years old subjects and 4.5 mg/kg/day for ≥12 years old subjects)
Part D - All Tumor Types TMT 0.032 mg/kg/Day + 100% DRB RP2D
Participants under 6 years of age (all tumor types in Part D) treated with a combination therapy of trametinib (0.032 mg/kg/day) with 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day)
Part D - All Tumor Types TMT 0.025 mg/kg/Day + 100% DRB RP2D
Participants (all tumor types in Part D) treated with a combination therapy of trametinib (0.025 mg/kg/day) plus 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day for \<12 years old subjects and 4.5 mg/kg/day for ≥12 years old subjects)
| Group | Source count |
|---|---|
| Part A - TMT 0.0125 mg/kg/Day | 3 |
| Part A - TMT 0.025 mg/kg/Day | 18 |
| Part A - TMT 0.032 mg/kg/Day | 9 |
| Part A - TMT 0.04 mg/kg/Day | 15 |
| Part B - Neuroblastoma | 9 |
| Part B - LGG Fusion | 10 |
| Part B - NF-1 With PN | 10 |
| Part B - BRAF V600 Mutant Solid Tumor | 9 |
| Part B - All Tumor Types TMT 0.025 mg/kg/Day | 38 |
| Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D | 1 |
| Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D | 1 |
| Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D | 6 |
| Part D - LGG | 20 |
| Part D - LCH | 6 |
| Part D - All Tumor Types TMT 0.032 mg/kg/Day + 100% DRB RP2D | 5 |
| Part D - All Tumor Types TMT 0.025 mg/kg/Day + 100% DRB RP2D | 21 |
Reported measurements
Source class 1
| Group | Value | Spread | Lower | Upper | Comment |
|---|---|---|---|---|---|
| Part A - TMT 0.0125 mg/kg/Day | 138 | 24.8 | Not reported | Not reported | Not reported |
| Part A - TMT 0.025 mg/kg/Day | 334 | 27.1 | Not reported | Not reported | Not reported |
| Part A - TMT 0.032 mg/kg/Day | 364 | 16.9 | Not reported | Not reported | Not reported |
| Part A - TMT 0.04 mg/kg/Day | 511 | 20.7 | Not reported | Not reported | Not reported |
| Part B - Neuroblastoma | 362 | 36.0 | Not reported | Not reported | Not reported |
| Part B - LGG Fusion | 316 | 40.4 | Not reported | Not reported | Not reported |
| Part B - NF-1 With PN | 323 | 25.1 | Not reported | Not reported | Not reported |
| Part B - BRAF V600 Mutant Solid Tumor | 379 | 42.8 | Not reported | Not reported | Not reported |
| Part B - All Tumor Types TMT 0.025 mg/kg/Day | 343 | 35.8 | Not reported | Not reported | Not reported |
| Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D | 290 | Not reported | Not reported | Not reported | Not reported |
| Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D | 331 | Not reported | Not reported | Not reported | Not reported |
| Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D | 236 | 28.4 | Not reported | Not reported | Not reported |
| Part D - LGG | 308 | 20.0 | Not reported | Not reported | Not reported |
| Part D - LCH | 186 | 23.7 | Not reported | Not reported | Not reported |
| Part D - All Tumor Types TMT 0.032 mg/kg/Day + 100% DRB RP2D | 228 | 33.1 | Not reported | Not reported | Not reported |
| Part D - All Tumor Types TMT 0.025 mg/kg/Day + 100% DRB RP2D | 286 | 28.4 | Not reported | Not reported | Not reported |
Complete source fields
- classes
- categories
- measurements
- group Id
- OG000
- spread
- 24.8
- value
- 138
- group Id
- OG001
- spread
- 27.1
- value
- 334
- group Id
- OG002
- spread
- 16.9
- value
- 364
- group Id
- OG003
- spread
- 20.7
- value
- 511
- group Id
- OG004
- spread
- 36.0
- value
- 362
- group Id
- OG005
- spread
- 40.4
- value
- 316
- group Id
- OG006
- spread
- 25.1
- value
- 323
- group Id
- OG007
- spread
- 42.8
- value
- 379
- group Id
- OG008
- spread
- 35.8
- value
- 343
- group Id
- OG009
- value
- 290
- group Id
- OG010
- value
- 331
- group Id
- OG011
- spread
- 28.4
- value
- 236
- denoms
- counts
- group Id
- OG000
- value
- 3
- group Id
- OG001
- value
- 18
- group Id
- OG002
- value
- 9
- group Id
- OG003
- value
- 15
- group Id
- OG004
- value
- 9
- group Id
- OG005
- value
- 10
- group Id
- OG006
- value
- 10
- group Id
- OG007
- value
- 9
- group Id
- OG008
- value
- 38
- group Id
- OG009
- value
- 1
- group Id
- OG010
- value
- 1
- group Id
- OG011
- value
- 6
- units
- Participants
- description
- Pharmacokinetic (PK) parameters were calculated based on trametinib plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for area under the curve calculation. The duration of the dosing interval (tau) was 24 hours for trametinib.
- dispersion Type
- Geometric Coefficient of Variation
- groups
- description
- Participants treated with trametinib 0.0125 mg/kg/day
- id
- OG000
- title
- Part A - TMT 0.0125 mg/kg/Day
- description
- Participants treated with trametinib 0.025 mg/kg/day
- id
- OG001
- title
- Part A - TMT 0.025 mg/kg/Day
- description
- Participants under 6 years of age treated with trametinib 0.032 mg/kg/day
- id
- OG002
- title
- Part A - TMT 0.032 mg/kg/Day
- description
- Participants treated with trametinib 0.04 mg/kg/day
- id
- OG003
- title
- Part A - TMT 0.04 mg/kg/Day
- description
- Participants with refractory or relapsed neuroblastoma treated with trametinib 0.025 mg/kg/day
- id
- OG004
- title
- Part B - Neuroblastoma
- description
- Participants with recurrent or unresectable low grade glioma (LGG) with BRAF tandem duplication with fusion treated with trametinib 0.025 mg/kg/day
- id
- OG005
- title
- Part B - LGG Fusion
- description
- Participants with neurofibromatosis Type -1 associated plexiform neurofibromas (NF-1 with PN) treated with trametinib 0.025 mg/kg/day
- id
- OG006
- title
- Part B - NF-1 With PN
- description
- Participants with BRAF V600 mutant solid tumors treated with trametinib 0.025 mg/kg/day
- id
- OG007
- title
- Part B - BRAF V600 Mutant Solid Tumor
- description
- Participants (all tumor types in Part B) treated with trametinib 0.025 mg/kg/day
- id
- OG008
- title
- Part B - All Tumor Types TMT 0.025 mg/kg/Day
- description
- Participants treated with a combination therapy of trametinib (0.025 mg/kg/day) plus 50% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (2.63 mg/kg/day for \<12 years old subjects and 2.25 mg/kg/day for ≥12 years old subjects)
- id
- OG009
- title
- Part C - TMT 0.025 mg/kg/Day + 50% DRB RP2D
- description
- Participants treated with a combination therapy of trametinib (0.025 mg/kg/day) plus 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day for \<12 years old subjects and 4.5 mg/kg/day for ≥12 years old subjects)
- id
- OG010
- title
- Part C - TMT 0.025 mg/kg/Day + 100% DRB RP2D
- description
- Participants under 6 years of age treated with a combination therapy of trametinib (0.032 mg/kg/day) with 100% of the recommended phase II dose (RP2D) of dabrafenib monotherapy (5.25 mg/kg/day)
- id
- OG011
- title
- Part C - TMT 0.032 mg/kg/Day + 100% DRB RP2D
- param Type
- GEOMETRIC_MEAN
- 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 with a value for the outcome measure
- 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
- Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau at Steady-state (AUCtau) of Trametinib When Administered Alone and in Combination With Dabrafenib
- type
- SECONDARY
- unit Of Measure
- hours*ng/mL
Download exact source JSON → · Snapshot ctgov-results-191f4516d4760045304b24a0
Preserved source evidence · Independent clinical review pending · Not medical advice