This is an open-label, non-randomized, two-period, cross-over, mass balance study that will evaluate the recovery, excretion, and pharmacokinetics of a single intravenous (IV) dose of \[14C\]-GSK2140944 (Period 1) and a single oral dose of \[14C\]-GSK2140944 ( Period 2) in 6 healthy male subjects. The results from this study will aid in the design of future clinical pharmacology studies such as the thorough corrected QT interval study, special population studies (renal, hepatic, critically ill patients), potential drug interaction studies, and will help to establish safe and efficacious intravenous and oral dosing regimens.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
6
GSK2140944 (1 gram) for Injection will be supplied as powder for injection containing \[14C\] GSK2140944. Non sterile powder is to be dissolved aseptically in sterile water for injection to a concentration of 4 mg/mL free base equivalent. IV solution is prepared by sterile filtration. 250 mL of IV solution, equivalent to 1000 mg GSK2140944, is then administered intravenously.
GSK2140944 Capsule (2 gram) will be supplied as powder in capsule containing \[14C\] GSK2140944. Powder is to be filled in empty capsule to achieve 200-400 mg strength per capsules as free base equivalent. Sufficient capsules are administered to provide the required total dose of 2 gram as free base.
GSK Investigational Site
London, United Kingdom
GSK2140944 PK parameters following single IV or oral doses of [14C]-GSK2140944
From the plasma concentration-time and blood/plasma radioactivity concentration-time data, the following pharmacokinetic parameters will be determined, as data permit: maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve \[AUC(0-t) and AUC(0-∞)\], and apparent terminal phase half-life (t1/2). Systemic clearance (CL) and volume of distribution (Vdss) of GSK2140944 may be calculated for IV regimen only.
Time frame: Pre-dose and post dose(0 minute [min], 15 min, 30 min, 60 min, 120 min, 2.5 hour[hr], 3 hr, 4 hr, 6 hr, 6.5 hr, 8 hr, 12 hr, 16 hr, 24 hr, 48 hr, 72hr, 96 hr, 120hr, 144 hr, 168 hr, 48 hr, 72 hr, 96 hr, 120 hr, 144 hr and 168 hr) of each treatment period
Total recovery of radioactivity in urine and feces following separate single IV and oral doses of [14C]-GSK2140944
Total recovery of radioactivity in urine and feces is defined as a percentage of total radioactive dose in each interval and cumulatively.
Time frame: Pre-dose and post dose(0-6 hr, 6 12 hr, 12 24 hr, 48 hr, 72 hr, 96 hr, 120 hr, 144 hr, 168 hr, 48 hr, 72 hr, 96 hr, 120 hr, 144 hr and 168 hr) of each treatment period
Number of subjects with adverse events (AE)
Time frame: Up to 7 weeks
Safety and tolerability of GSK2140944 after single IV and oral doses as assessed by concomitant medications review
Time frame: Up to 7 weeks
Safety and tolerability of GSK2140944 after single IV and oral doses as assessed by clinical laboratory tests
clinical laboratory tests includes hematology, clinical chemistry, urinalysis
Time frame: Day 1 and Day 8 of each treatment period
Safety and tolerability of GSK2140944 after single IV and oral doses as assessed by electrocardiogram (ECG)
Single 12-lead ECGs will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT interval (QTc) intervals.
Time frame: Day 1 (Pre dose and 1 hr, 2 hr, 4 hr and 8 hr post dose)and Day 8 of each treatment period
Safety and tolerability of GSK2140944 after single IV and oral doses as assessed by vital signs
Vital sign measurements to be measurement include systolic and diastolic blood pressure, pulse rate and temperature.
Time frame: Day 1 (Pre dose and 1 hr, 2 hr, 4 hr and 8 hr post dose)and Day 8 of each treatment period
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