The purpose of this study is to determine the absolute oral bioavailability and intravenous pharmacokinetics of GSK962040. The oral dose of 50 mg has been selected because it was well tolerated following single oral administration and it is considered to be within therapeutic dose range. The need to characterize the intravenous disposition of GSK962040 is in anticipation of drug use in special populations such as critically.
GSK962040 is a selective non-peptide motilin receptor agonist which is being developed for the treatment of conditions associated with slow rates of gastric emptying. The purpose of this study is to determine the absolute bioavailability and the metabolic profile of GSK962040. Subjects will be administered a single oral dose of 50 mg followed by a single intravenous dose of 10 mL containing 100 microgram (not more than 270 nCi, 10 kBq) 14C GSK962040, administered by infusion over 15 minutes, beginning at 90 min after administration of the oral dose (approximate Cmax). The oral dose of 50 mg was well tolerated following single oral administration and is predicted to be a therapeutic dose. There is need to characterize GSK962040 disposition in anticipation of drug use in special populations such as critically ill patients. The intravenous (infused) microdose (100 microgram) is 500-fold lower than the oral dose, therefore exposure to GSK962040 originating from the infused microdose is considered negligible.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
8
GSK Investigational Site
Nottingham, United Kingdom
PK parameters for GSK962040 following i.v. dose: AUC(0-inf), Cmax, tmax, t½, systemic clearance (CL), renal clearance (CLr), metabolic clearance (CLm), volume of distribution (Vss), and mean residence time (MRT).
Time frame: 14 days
PK parameters following oral dose: AUC(0-inf), AUC(0-t), Cmax, tmax, t½, tlag, CLoral and absolute bioavailability (F).
Time frame: 14 days
Adverse Events
Time frame: 14 days
Urine and fecal recovery of GSK962040 following a single oral and i.v. dose of [14C] GSK962040.
Time frame: 14 days
Urine, fecal recovery and total recovery of radiocarbon (as a percentage of total radioactive dose in each interval and cumulative)
Time frame: 14 days
Characterization and semi-quantitation of GSK962040-related metabolites in plasma, urine, and fecal homogenates following a single oral and i.v. dose of [14C] GSK962040.
Time frame: 14 days
Vital signs
Time frame: 14 days
ECGs
Time frame: 14 days
Clinical lab assessments
Time frame: 14 days
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