{"classes":[{"categories":[{"measurements":[{"groupId":"OG000","lowerLimit":"1.03","upperLimit":"2.00","value":"2.00"},{"groupId":"OG001","lowerLimit":"1.03","upperLimit":"6.00","value":"2.00"},{"groupId":"OG002","lowerLimit":"1.00","upperLimit":"2.10","value":"2.00"},{"groupId":"OG003","lowerLimit":"1.00","upperLimit":"2.00","value":"1.50"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"6"},{"groupId":"OG001","value":"8"},{"groupId":"OG002","value":"12"},{"groupId":"OG003","value":"8"}],"units":"Participants"}],"title":"DAB Day 15"},{"categories":[{"measurements":[{"groupId":"OG001","lowerLimit":"1.00","upperLimit":"2.00","value":"1.54"},{"groupId":"OG002","lowerLimit":"1.00","upperLimit":"2.03","value":"1.53"},{"groupId":"OG003","lowerLimit":"1.00","upperLimit":"4.03","value":"2.04"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"8"},{"groupId":"OG002","value":"12"},{"groupId":"OG003","value":"8"}],"units":"Participants"}],"title":"DAB Day 21"},{"categories":[{"measurements":[{"groupId":"OG000","lowerLimit":"2.00","upperLimit":"2.03","value":"2.00"},{"groupId":"OG001","lowerLimit":"1.03","upperLimit":"8.00","value":"2.00"},{"groupId":"OG002","lowerLimit":"2.00","upperLimit":"4.03","value":"2.00"},{"groupId":"OG003","lowerLimit":"2.00","upperLimit":"2.00","value":"2.00"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"6"},{"groupId":"OG001","value":"8"},{"groupId":"OG002","value":"12"},{"groupId":"OG003","value":"8"}],"units":"Participants"}],"title":"GSK2285403 Day 15"},{"categories":[{"measurements":[{"groupId":"OG001","lowerLimit":"0.00","upperLimit":"2.00","value":"1.97"},{"groupId":"OG002","lowerLimit":"1.00","upperLimit":"2.03","value":"2.00"},{"groupId":"OG003","lowerLimit":"1.00","upperLimit":"6.00","value":"2.07"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"8"},{"groupId":"OG002","value":"12"},{"groupId":"OG003","value":"8"}],"units":"Participants"}],"title":"GSK2285403 Day 21"},{"categories":[{"measurements":[{"groupId":"OG000","lowerLimit":"4.00","upperLimit":"8.00","value":"6.00"},{"groupId":"OG001","lowerLimit":"0.00","upperLimit":"6.30","value":"4.96"},{"groupId":"OG002","lowerLimit":"1.00","upperLimit":"8.02","value":"4.17"},{"groupId":"OG003","lowerLimit":"4.00","upperLimit":"8.00","value":"4.10"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"6"},{"groupId":"OG001","value":"8"},{"groupId":"OG002","value":"12"},{"groupId":"OG003","value":"8"}],"units":"Participants"}],"title":"GSK2298683 Day 15"},{"categories":[{"measurements":[{"groupId":"OG001","lowerLimit":"1.00","upperLimit":"6.00","value":"4.00"},{"groupId":"OG002","lowerLimit":"1.00","upperLimit":"6.00","value":"4.00"},{"groupId":"OG003","lowerLimit":"2.00","upperLimit":"8.07","value":"4.02"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"8"},{"groupId":"OG002","value":"12"},{"groupId":"OG003","value":"8"}],"units":"Participants"}],"title":"GSK2298683 Day 21"},{"categories":[{"measurements":[{"groupId":"OG000","lowerLimit":"0.00","upperLimit":"4.17","value":"0.00"},{"groupId":"OG001","lowerLimit":"0.00","upperLimit":"8.00","value":"2.94"},{"groupId":"OG002","lowerLimit":"1.00","upperLimit":"8.02","value":"4.17"},{"groupId":"OG003","lowerLimit":"0.00","upperLimit":"2.00","value":"1.52"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"6"},{"groupId":"OG001","value":"8"},{"groupId":"OG002","value":"12"},{"groupId":"OG003","value":"8"}],"units":"Participants"}],"title":"GSK2167542 Day 15"},{"categories":[{"measurements":[{"groupId":"OG001","lowerLimit":"1.00","upperLimit":"2.32","value":"2.00"},{"groupId":"OG002","lowerLimit":"0.00","upperLimit":"8.00","value":"1.01"},{"groupId":"OG003","lowerLimit":"0.00","upperLimit":"8.15","value":"1.50"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"8"},{"groupId":"OG002","value":"12"},{"groupId":"OG003","value":"8"}],"units":"Participants"}],"title":"GSK2167542 Day 21"}],"denoms":[{"counts":[{"groupId":"OG000","value":"6"},{"groupId":"OG001","value":"8"},{"groupId":"OG002","value":"12"},{"groupId":"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.","dispersionType":"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"}],"paramType":"MEDIAN","populationDescription":"PK Population. Only those participants who were available at the indicated time points were analyzed.","reportingStatus":"POSTED","timeFrame":"Day 15 and Day 21","title":"Part B: Tmax of Dabrafenib and Its Metabolite in Combination With Trametinib","type":"SECONDARY","unitOfMeasure":"Hours"}