biostudies-literatureNebot NNovartis Pharmaceuticals CorporationNCI NIH HHS764-775https://www.ebi.ac.uk/biostudies/studies/S-EPMC5867134biostudies-literatureUnknown84(4)<h4>Aims</h4>The effect of repeat oral supratherapeutic dosing of the BRAF inhibitor dabrafenib on QTc interval was assessed in patients with BRAF V600-mutant tumours.<h4>Methods</h4>Part 1 of this phase 1, multicentre, 2-part study (BRF113773/NCT01738451) assessed safety/tolerability of dabrafenib 225 or 300 mg twice daily (BID) to inform part 2 dosing. Patients in part 2 received dabrafenib-matched placebo on day -1, single-dose dabrafenib 300 mg on day 1, 300 mg BID on days 2 to 7, and 300 mg on day 8 (morning), followed by 24-h Holter electrocardiographic monitoring and pharmacokinetics sample collection each dose day. Pharmacokinetics/pharmacodynamics analysis assessed combined dabrafenib and metabolite effects on QTc interval.<h4>Results</h4>Part 1 (n = 12) determined supratherapeutiBritish journal of clinical pharmacologyEvaluation of the effect of dabrafenib and metabolites on QTc interval in patients with BRAF V600-mutant tumours.PMC5867134P30 CA054174Sarantopoulos JGrossmann KFNebot NArkenau HTCarson SWChandler JCMookerjee BSt-Pierre ATang LMak GLickliter JDWeickhardt AInfante JRGordon MSHayes SfalseEvaluation of the effect of dabrafenib and metabolites on QTc interval in patients with BRAF V600-mutant tumours.<h4>Aims</h4>The effect of repeat oral supratherapeutic dosing of the BRAF inhibitor dabrafenib on QTc interval was assessed in patients with BRAF V600-mutant tumours.<h4>Methods</h4>Part 1 of this phase 1, multicentre, 2-part study (BRF113773/NCT01738451) assessed safety/tolerability of dabrafenib 225 or 300 mg twice daily (BID) to inform part 2 dosing. Patients in part 2 received dabrafenib-matched placebo on day -1, single-dose dabrafenib 300 mg on day 1, 300 mg BID on days 2 to 7, and 300 mg on day 8 (morning), followed by 24-h Holter electrocardiographic monitoring and pharmacokinetics sample collection each dose day. Pharmacokinetics/pharmacodynamics analysis assessed combined dabrafenib and metabolite effects on QTc interval.<h4>Results</h4>Part 1 (n = 12) determined supratherapeuti2018-01-01T00:00:00Z2018 Apr2026-04-29T16:18:18.345Z2019-06-06T19:11:30ZS-EPMC58671342924328710.1111/bcp.13488