{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nebot N"],"funding":["Novartis Pharmaceuticals Corporation","NCI NIH HHS"],"pagination":["764-775"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5867134"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["84(4)"],"pubmed_abstract":["<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 supratherapeuti"],"journal":["British journal of clinical pharmacology"],"pubmed_title":["Evaluation of the effect of dabrafenib and metabolites on QTc interval in patients with BRAF V600-mutant tumours."],"pmcid":["PMC5867134"],"funding_grant_id":["P30 CA054174"],"pubmed_authors":["Sarantopoulos J","Grossmann KF","Nebot N","Arkenau HT","Carson SW","Chandler JC","Mookerjee B","St-Pierre A","Tang L","Mak G","Lickliter JD","Weickhardt A","Infante JR","Gordon MS","Hayes S"],"additional_accession":[]},"is_claimable":false,"name":"Evaluation of the effect of dabrafenib and metabolites on QTc interval in patients with BRAF V600-mutant tumours.","description":"<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 supratherapeuti","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Apr","modification":"2026-04-29T16:18:18.345Z","creation":"2019-06-06T19:11:30Z"},"accession":"S-EPMC5867134","cross_references":{"pubmed":["29243287"],"doi":["10.1111/bcp.13488"]}}