{"classes":[{"categories":[{"measurements":[{"groupId":"OG000","lowerLimit":"1.00","upperLimit":"2.00","value":"1.00"},{"groupId":"OG001","lowerLimit":"1.00","upperLimit":"4.00","value":"2.00"},{"groupId":"OG002","lowerLimit":"1.00","upperLimit":"2.00","value":"1.00"},{"groupId":"OG003","lowerLimit":"1.00","upperLimit":"24.0","value":"2.00"},{"groupId":"OG004","lowerLimit":"1.00","upperLimit":"4.00","value":"1.00"},{"groupId":"OG005","lowerLimit":"1.00","upperLimit":"2.00","value":"1.50"},{"groupId":"OG006","lowerLimit":"1.00","upperLimit":"2.00","value":"1.00"},{"groupId":"OG007","lowerLimit":"1.00","upperLimit":"2.00","value":"1.00"},{"groupId":"OG008","lowerLimit":"1.00","upperLimit":"4.00","value":"1.00"},{"groupId":"OG009","lowerLimit":"1.00","upperLimit":"1.00","value":"1.00"},{"groupId":"OG010","lowerLimit":"1.00","upperLimit":"1.00","value":"1.00"},{"groupId":"OG011","lowerLimit":"1.00","upperLimit":"2.00","value":"1.50"},{"groupId":"OG012","lowerLimit":"1.00","upperLimit":"3.00","value":"2.00"},{"groupId":"OG013","lowerLimit":"1.00","upperLimit":"4.00","value":"1.00"},{"groupId":"OG014","lowerLimit":"1.00","upperLimit":"1.00","value":"1.00"},{"groupId":"OG015","lowerLimit":"1.00","upperLimit":"4.00","value":"2.00"}]}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"3"},{"groupId":"OG001","value":"19"},{"groupId":"OG002","value":"9"},{"groupId":"OG003","value":"16"},{"groupId":"OG004","value":"9"},{"groupId":"OG005","value":"10"},{"groupId":"OG006","value":"10"},{"groupId":"OG007","value":"9"},{"groupId":"OG008","value":"38"},{"groupId":"OG009","value":"1"},{"groupId":"OG010","value":"1"},{"groupId":"OG011","value":"6"},{"groupId":"OG012","value":"20"},{"groupId":"OG013","value":"6"},{"groupId":"OG014","value":"5"},{"groupId":"OG015","value":"21"}],"units":"Participants"}],"description":"Pharmacokinetic (PK) parameters were calculated based on trametinib plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose.","dispersionType":"Full Range","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"},{"description":"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)","id":"OG012","title":"Part D - LGG"},{"description":"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)","id":"OG013","title":"Part D - LCH"},{"description":"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)","id":"OG014","title":"Part D - All Tumor Types TMT 0.032 mg/kg/Day + 100% DRB RP2D"},{"description":"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)","id":"OG015","title":"Part D - All Tumor Types TMT 0.025 mg/kg/Day + 100% DRB RP2D"}],"paramType":"MEDIAN","populationDescription":"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","reportingStatus":"POSTED","timeFrame":"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":"Time to Reach Maximum Plasma Concentration (Tmax) of Trametinib When Administered Alone and in Combination With Dabrafenib","type":"SECONDARY","unitOfMeasure":"hours"}