The study is a Phase 1, open-label study designed to characterize the absorption, distribution, metabolism and excretion of GSK2118436 following administration of a single oral 14C labeled dose of GSK2118436 as a suspension in subjects with BRAF mutation positive tumors.
GSK2118436 is an orally administered, potent and selective small molecule BRAF inhibitor that is being developed for the treatment of BRAF mutation-positive tumors. The study is a Phase 1, open-label study designed to characterize the absorption, distribution, metabolism and excretion of GSK2118436 following administration of a single oral 14C labeled dose of GSK2118436 as a suspension in subjects with BRAF mutation positive tumors. A sufficient number of subjects will be enrolled to complete approximately four subjects. Following completion of the study, subjects may continue dosing with GSK2118436 in the rollover study, BRF114144.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
4
A single oral dose of 95 mg of GSK2118436 containing approximately 80 µCi of radioactivity
GSK Investigational Site
Tacoma, Washington, United States
• Excretion of radioactivity in urine following oral administration of [14C]GSK2118436
Time frame: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Excretion of radioactivity in feces following oral administration of [14C]GSK2118436
Time frame: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Quantity of GSK2118436 metabolites in plasma
Time frame: Pre-dose, and up to 48 hours post dose.
• Potential covalent binding of drug-related material to plasma proteins
Time frame: Pre-dose, and up to 48 hours post dose.
• Blood total radioactivity
Time frame: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Blood:plasma ratio of total drug-related material (radioactivity)
Time frame: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Area under the plasma-concentration time curve (AUC) of plasma GSK2118436 and metabolites
Time frame: Pre-dose, and up to 48 hours post dose.
• Number of subjects with adverse events as a measure of safety and tolerability
Time frame: From date of dosing until transition to rollover protocol BRF114144 (approximately 4 - 11 days) or study follow up visit if subject does not transition to BRF114144 (approximately 14 - 21 days)
• Quantity of GSK2118436 metabolites in feces
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Time frame: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Quantity of GSK2118436 metabolites in urine
Time frame: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Character of GSK2118436 metabolites in plasma
Time frame: Pre-dose, and up to 48 hours post dose.
• Character of GSK2118436 metabolites in feces
Time frame: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Character of GSK2118436 metabolites in urine
Time frame: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Plasma total radioactivity
Time frame: Pre-dose, and post-dose for a minimum of 96 hours, and a maximum of 240 hours after dosing.
• Maximum plasma concentration (Cmax) of plasma GSK2118436 and metabolites
Time frame: Pre-dose, and up to 48 hours post dose
• Time to Cmax (Tmax) of plasma GSK2118436 and metabolites
Time frame: Pre-dose, and up to 48 hours post dose
• Terminal half-life (t1/2) of plasma GSK2118436 and metabolites
Time frame: Pre-dose, and up to 48 hours post dose.