{"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"0.788"}]}],"title":"Effect of weight on CL/F"},{"categories":[{"measurements":[{"groupId":"OG000","value":"1.24"}]}],"title":"Effect of sex on CL/F"},{"categories":[{"measurements":[{"groupId":"OG000","value":"0.679"}]}],"title":"Effect of weight on Q/F"},{"categories":[{"measurements":[{"groupId":"OG000","value":"0.876"}]}],"title":"Effect of combination with dabrafenib on relative bioavailability F1"}],"denoms":[{"counts":[{"groupId":"OG000","value":"133"}],"units":"Participants"}],"description":"The population pharmacokinetic (PopPK) model of trametinib can be described using a two-compartment model with dual sequential 1st order absorption (Ka1, Ka2) and 1st order elimination. Sex and weight are significant covariates on apparent clearance (CL/F), and weight is also a significant covariate on apparent intercompartmental clearance (Q/F). Use of dabrafenib, yes or no, is a covariate on the relative bioavailability of trametinib, reflecting the effect of dabrafenib on the PK of trametinib.\n\nThe estimates of these covariates (effect of weight on CL/F, effect of sex on CL/F, effect of weight on Q/F, effect of combination with dabrafenib on relative bioavailability F1) calculated with the PopPK model are summarized in this record.","groups":[{"description":"Participants in the study (all doses and all tumor types) with available pharmacokinetic data","id":"OG000","title":"Part A, B, C and D - All Participants With PK Data"}],"paramType":"NUMBER","populationDescription":"All subjects who received at least one dose of trametinib in Part A, B, C and D and provided an evaluable PK profile. All trametinib and dabrafenib concentration-time data were combined and included in a population PK analysis that examined the influence of demographics on the PK of study treatment.","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":"Significant Covariates Estimated With a PopPK Model","type":"SECONDARY","unitOfMeasure":"no units"}