{"analyses":[{"ciLowerLimit":"0.89","ciNumSides":"TWO_SIDED","ciPctValue":"90","ciUpperLimit":"1.69","estimateComment":"Geometric mean ratio (Day 21 Dabrafenib 150 mg BID+Trametinib 2 mg QD/Day 21 Dabrafenib 150 mg BID alone) and the corresponding 90% confidence interval were provided.","groupIds":["OG001","OG003"],"nonInferiorityComment":"Following loge transformation, AUC(0-tau) of dabrafenib was analyzed by a linear mixed effect model with dosing chort and day as fixed effects and subject as random effect. Based on the model, geometric mean ratio (Day 21 Dabrafenib 150 mg BID+Trametinib 2 mg QD/Day 21 Dabrafenib 150 mg BID alone) and the corresponding 90% confidence interval were provided.","nonInferiorityType":"NON_INFERIORITY_OR_EQUIVALENCE","paramType":"Geometric Mean Ratio","paramValue":"1.23"},{"ciLowerLimit":"0.84","ciNumSides":"TWO_SIDED","ciPctValue":"90","ciUpperLimit":"1.44","estimateComment":"Geometric mean ratio (HPMC/Gelatin) and the corresponding 90% CI were provided for BRAF dose level 150 mg BID.","groupIds":["OG001","OG003"],"nonInferiorityComment":"Following loge tranformation, AUC(0-tau) of dabrafenib after repeat doses from the pooled data in Part B and D were analyzed by a linear model with the following fixed effects as categorical variables: Capsule type (Gelatin or HPMC), BRAF dose (75 or 150 mg BID), Capsule type by BRAF dose interaction, Day (Day 15 or 21), MEK dose (0, 1, 1.5, 2 or 2 mg QD). Geometric mean ratio (HPMC/Gelatin) and the corresponding 90% CI were then provided for BRAF dose level 150 mg BID.","nonInferiorityType":"NON_INFERIORITY_OR_EQUIVALENCE","paramType":"Geometric Mean Ratio","paramValue":"1.10"}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","lowerLimit":"3008","upperLimit":"4293","value":"3593"},{"groupId":"OG001","lowerLimit":"4288","upperLimit":"9872","value":"6507"},{"groupId":"OG002","lowerLimit":"3525","upperLimit":"6051","value":"4618"},{"groupId":"OG003","lowerLimit":"5355","upperLimit":"10037","value":"7331"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"15"},{"groupId":"OG001","value":"14"},{"groupId":"OG002","value":"15"},{"groupId":"OG003","value":"15"}],"units":"Participants"}],"title":"AUC (0-tau), Day 1"},{"categories":[{"measurements":[{"groupId":"OG000","lowerLimit":"2390","upperLimit":"3816","value":"3020"},{"groupId":"OG001","lowerLimit":"3511","upperLimit":"6194","value":"4663"},{"groupId":"OG002","lowerLimit":"2679","upperLimit":"4403","value":"3434"},{"groupId":"OG003","lowerLimit":"4608","upperLimit":"7517","value":"5886"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"15"},{"groupId":"OG001","value":"14"},{"groupId":"OG002","value":"15"},{"groupId":"OG003","value":"15"}],"units":"Participants"}],"title":"AUC (0-tau), Day 21"},{"categories":[{"measurements":[{"groupId":"OG000","lowerLimit":"3325","upperLimit":"4770","value":"3982"},{"groupId":"OG001","lowerLimit":"4830","upperLimit":"11005","value":"7291"},{"groupId":"OG002","lowerLimit":"4192","upperLimit":"6755","value":"5321"},{"groupId":"OG003","lowerLimit":"5860","upperLimit":"11341","value":"8152"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"15"},{"groupId":"OG001","value":"14"},{"groupId":"OG002","value":"15"},{"groupId":"OG003","value":"15"}],"units":"Participants"}],"title":"AUC (0-inf), Day 1"},{"denoms":[{"counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"0"},{"groupId":"OG003","value":"0"}],"units":"Participants"}],"title":"AUC (0-inf), Day 21"}],"denoms":[{"counts":[{"groupId":"OG000","value":"15"},{"groupId":"OG001","value":"14"},{"groupId":"OG002","value":"15"},{"groupId":"OG003","value":"15"}],"units":"Participants"}],"description":"The PK parameters were determined for area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration AUC (0-tau) and from time zero (pre-dose) extrapolated to infinite time AUC (0-inf). Blood samples for PK analysis of the metabolites of dabrafenib were obtained at Day 1 and Day 21 pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 24 hours (24 hour only on Day 1) post-dose administration.","dispersionType":"95% Confidence Interval","groups":[{"description":"Participants received dabrefinib 75 mg HPMC capsules BID. These participants, after completion of serial PK collection in the first treatment period, were allowed to continue with dabrafenib 75 mg BID and trametinib 2 mg tablets QD as combination dosing starting on Day 29.","id":"OG000","title":"Part D: Dabrafenib (DAB) 75 mg to DAB 75 mg + Trametinib 2 mg"},{"description":"Participants received dabrefinib 150 mg HPMC capsules BID. These participants, after completion of serial PK collection in the first treatment period, were allowed to continue with dabrafenib 150 mg BID and trametinib 2 mg tablets QD as combination dosing starting on Day 29.","id":"OG001","title":"Part D: Dabrafenib 150 mg to DAB 150 mg + Trametinib 2 mg"},{"description":"Participants received dabrefinib 75 mg HPMC capsules BID and trametinib 2 mg tablets QD.","id":"OG002","title":"Part D: Dabrafenib 75 mg + Trametinib 2 mg"},{"description":"Participants received dabrefinib 150 mg HPMC capsules BID and trametinib 2 mg tablets QD.","id":"OG003","title":"Part D: Dabrafenib 150 mg + Trametinib 2 mg"}],"paramType":"GEOMETRIC_MEAN","populationDescription":"PK Population. Only participants available at the indicated timepoints were analyzed.","reportingStatus":"POSTED","timeFrame":"Day 1 and Day 21","title":"Part D (Analyte=GSK2118436): AUC (0-tau) and AUC (0-inf) of Single and Repeat Doses of Dabrafenib Alone and in Combination With Trametinib","type":"PRIMARY","unitOfMeasure":"ng*hr/mL"}