{"analyses":[{"ciLowerLimit":"0.85","ciNumSides":"TWO_SIDED","ciPctValue":"90","ciUpperLimit":"1.19","estimateComment":"Geometric mean ratio (Day 15 AUC(0-inf)/ Day 1 AUC(0-inf)) and 90% confidence interval for dabrafenib were calculated.","groupIds":["OG000","OG001"],"nonInferiorityComment":"AUC(0-t) of dabrafenib was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.","nonInferiorityType":"NON_INFERIORITY_OR_EQUIVALENCE","paramType":"Geometric Mean Ratio","paramValue":"1.01"},{"ciLowerLimit":"0.82","ciNumSides":"TWO_SIDED","ciPctValue":"90","ciUpperLimit":"1.08","estimateComment":"Geometric mean ratio (Day 15 AUC(0-inf)/ Day 1 AUC(0-inf)) and 90% confidence interval for dabrafenib were calculated.","groupIds":["OG000","OG001"],"nonInferiorityComment":"AUC(0-inf) of dabrafenib was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.","nonInferiorityType":"NON_INFERIORITY_OR_EQUIVALENCE","paramType":"Geometric Mean Ratio","paramValue":"0.94"},{"ciLowerLimit":"0.84","ciNumSides":"TWO_SIDED","ciPctValue":"90","ciUpperLimit":"1.25","estimateComment":"Geometric mean ratio (Day 15 AUC(0-t)/ Day 1 AUC(0-t)) and 90% confidence interval for GSK2285403 were calculated.","groupIds":["OG000","OG001"],"nonInferiorityComment":"AUC(0-t) of GSK2285403 was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.","nonInferiorityType":"NON_INFERIORITY_OR_EQUIVALENCE","paramType":"Geometric Mean Ratio","paramValue":"1.02"},{"ciLowerLimit":"0.81","ciNumSides":"TWO_SIDED","ciPctValue":"90","ciUpperLimit":"1.03","estimateComment":"Geometric mean ratio (Day 15 AUC(0-inf)/ Day 1 AUC(0-inf)) and 90% confidence interval for GSK2285403 were calculated.","groupIds":["OG000","OG001"],"nonInferiorityComment":"AUC(0-inf) of GSK2285403 was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.","nonInferiorityType":"NON_INFERIORITY_OR_EQUIVALENCE","paramType":"Geometric Mean Ratio","paramValue":"0.92"},{"ciLowerLimit":"0.81","ciNumSides":"TWO_SIDED","ciPctValue":"90","ciUpperLimit":"1.29","estimateComment":"Geometric mean ratio (Day 15 AUC(0-t)/ Day 1 AUC(0-t)) and 90% confidence interval for GSK2298683 were calculated.","groupIds":["OG000","OG001"],"nonInferiorityComment":"AUC(0-t) of GSK2298683 was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.","nonInferiorityType":"NON_INFERIORITY_OR_EQUIVALENCE","paramType":"Geometric Mean Ratio","paramValue":"1.02"},{"ciLowerLimit":"0.76","ciNumSides":"TWO_SIDED","ciPctValue":"90","ciUpperLimit":"1.37","estimateComment":"Geometric mean ratio (Day 15 AUC(0-t)/ Day 1 AUC(0-t)) and 90% confidence interval for GSK2167542 were calculated.","groupIds":["OG000","OG001"],"nonInferiorityComment":"AUC(0-t) of GSK2167542 was log e transformed and analyzed by a linear mixed effect model with fixed effect for treatment (dabrafenib alone and combined with trametinib) and participant as a random effect. Geometric mean ratio (Day 15/Day 1) and 90% confidence interval were provided.","nonInferiorityType":"NON_INFERIORITY_OR_EQUIVALENCE","paramType":"Geometric Mean Ratio","paramValue":"1.02"}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","lowerLimit":"2205","upperLimit":"3390","value":"2734"},{"groupId":"OG001","lowerLimit":"2219","upperLimit":"3411","value":"2751"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"8"},{"groupId":"OG001","value":"8"}],"units":"Participants"}],"title":"GSK2118436 AUC (0-t)"},{"categories":[{"measurements":[{"groupId":"OG000","lowerLimit":"2578","upperLimit":"3797","value":"3128"},{"groupId":"OG001","lowerLimit":"2445","upperLimit":"3556","value":"2949"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"8"},{"groupId":"OG001","value":"8"}],"units":"Participants"}],"title":"GSK2118436 AUC (0-inf)"},{"categories":[{"measurements":[{"groupId":"OG000","lowerLimit":"1684","upperLimit":"2959","value":"2232"},{"groupId":"OG001","lowerLimit":"1899","upperLimit":"2753","value":"2287"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"8"},{"groupId":"OG001","value":"8"}],"units":"Participants"}],"title":"GSK2285403 AUC (0-t)"},{"categories":[{"measurements":[{"groupId":"OG000","lowerLimit":"2231","upperLimit":"3562","value":"2819"},{"groupId":"OG001","lowerLimit":"2097","upperLimit":"2974","value":"2497"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"8"},{"groupId":"OG001","value":"8"}],"units":"Participants"}],"title":"GSK2285403 AUC (0-inf)"},{"categories":[{"measurements":[{"groupId":"OG000","lowerLimit":"10347","upperLimit":"15738","value":"12761"},{"groupId":"OG001","lowerLimit":"10475","upperLimit":"16266","value":"13053"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"8"},{"groupId":"OG001","value":"8"}],"units":"Participants"}],"title":"GSK2298683 AUC (0-t)"},{"denoms":[{"counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"}],"units":"Participants"}],"title":"GSK2298683 AUC (0-inf)"},{"categories":[{"measurements":[{"groupId":"OG000","lowerLimit":"188","upperLimit":"390","value":"270"},{"groupId":"OG001","lowerLimit":"230","upperLimit":"332","value":"276"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"8"},{"groupId":"OG001","value":"8"}],"units":"Participants"}],"title":"GSK2167542 AUC (0-t)"},{"denoms":[{"counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"}],"units":"Participants"}],"title":"GSK2167542 AUC (0-inf)"}],"denoms":[{"counts":[{"groupId":"OG000","value":"8"},{"groupId":"OG001","value":"8"}],"units":"Participants"}],"description":"Blood samples for PK analysis of dabrafenib and its metabolites hydroxy-dabrafenib (GSK2285403), carboxy-dabrafenib (GSK2298683) and desmethyl-dabrafenib (GSK2167542) were obtained at pre-dose and at 1, 2, 3, 4, 6, 8, 10, and 24 hours after dabrafenib administration. AUC is defined as the area under the dabrafenib concentration-time curve as a measure of drug exposure. AUC (0-inf) is defined as the area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time. AUC (0-t) is defined as area under the concentration-time curve from time zero (pre-dose) to the last time of quantifiable concentration. Date are reported as geometric least square means.","dispersionType":"95% Confidence Interval","groups":[{"description":"Participants received a single dose of dabrafenib 75 mg gelatin capsules alone on Day 1.","id":"OG000","title":"Part A: Dabrafenib 75 mg"},{"description":"Participants received a single dose of dabrafenib 75 mg gelatin capsules with repeat dose trametinib (Day 15).","id":"OG001","title":"Part A: Dabrafenib 75 mg + Trametinib 2 mg"}],"paramType":"GEOMETRIC_MEAN","populationDescription":"PK Population","reportingStatus":"POSTED","timeFrame":"Day 15","title":"Part A: AUC (0-t) and AUC (0-inf) of Dabrafenib and Its Metabolites","type":"PRIMARY","unitOfMeasure":"ng*hour/mL (ng*hr/mL)"}