GSK1120212 is a reversible and highly selective allosteric inhibitor of MEK1 and MEK2 activation and kinase activity currently being developed for the treatment of malignant melanoma. This is a Phase I, open-label, non-randomized, single-dose study designed to characterize the absorption, distribution, metabolism, and elimination (ADME) of a single oral dose of MEK inhibitor \[14C\]GSK1120212 as a solution in male subjects with solid tumor malignancies. A sufficient number of subjects will be enrolled to complete approximately four evaluable subjects. Following completion of the study, subjects may elect to continue dosing with GSK1120212 in the rollover study, MEK114375.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
6
The 2 mg dose is based on clinical data from the ongoing FTIH study in which subjects have been dosed daily for greater than 21 days, as well as preclinical toxicity data.
GSK Investigational Site
Tacoma, Washington, United States
Total excretion of radioactivity
• Total and relative excretion of radioactivity in urine and feces following a single, 2 mg oral solution dose of \[14C\]GSK1120212
Time frame: 11 days
Total radioactivity concentration in blood and plasma
AUC(0- t), AUC(0-∞), Cmax, tmax and t1/2
Time frame: 11 days
Characterize and quantify metabolites in urine plasma and feces
Characterize and quantify metabolites of GSK1120212 in plasma, urine and feces (studied separately under a DMPK protocol).
Time frame: 11 days
Assess covalent binding of drug related material to plasma proteins
Assess percentage of drug-related material that covalently bonds to plasma proteins (studied separately under a DMPK protocol)
Time frame: 11 days
Blood:plasma ratio
Blood:plasma ratio of total drug-related material (radioactivity)
Time frame: 11 days
Pharmacokentic concentrations in plasma
Plasma GSK1120212 concentrations AUC(0-t), AUC(0-∞), Cmax, tmax, and t1/2
Time frame: 11 days
AEs
Number of adverse events (AEs)
Time frame: From dosing on Day 1 to Follow-up
Vital signs
Changes from baseline
Time frame: Screening, Day -1, Day 1, Day 5, and Follow-up
ECGs
Changes from baseline
Time frame: Screening, Day 1 pre-dose, 24 hours, Day 11 and Follow-up
Clinical Laboratory assessments
Changes from baslines
Time frame: Screening, Day -1, and Day 11
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