Infections, Respiratory Tract
Conditions
Keywords
oral, ADME, IV, antibiotic, healthy volunteer, [14C]-GSK2140944, mass balance, radiolabel
Brief summary
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.
Interventions
DRUGGSK2140944 for Injection
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.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
30 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* A subject will be eligible for inclusion in this study only if all of the following criteria apply: * Male aged between 30 and 55 years of age inclusive, at the time of signing the informed consent. * Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, vital signs, laboratory tests and cardiac monitoring. * A subject with a clinical abnormality or laboratory parameter outside the reference range for the population being studied may be included only if the Investigator feels and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body weight \>=50 kilogram and Body Mass Index within the range 19- 31 kilogram per square meter (inclusive). * Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and bilirubin \<=1.5xupper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * A history of regular bowel movements (averaging one or more bowel movements per day). * Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in Protocol. This criterion must be followed from the time of the first dose of study medication until four months after the last dose. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Exclusion criteria
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of \>21 units for males. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 ml) of beer, 1 glass (125 milliliter \[mL\]) of wine or 1 (25 mL) measure of spirits. * History of sensitivity to heparin or heparin-induced thrombocytopenia. * History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. * Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Subjects with a history of cholecystectomy must be excluded. * History of sensitivity to quinolones including photosensitivity and tendon rupture. * A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening or positive test for Human Immunodeficiency Virus (HIV) antibody. * A screening or Day -1 urinalysis positive for protein or glucose (greater than 1+ findings of protein or glucose). * A serum creatinine value between screening and Day -1 visit that is increased by more than 0.2 milligrams per decilitre (or 15.25 micromole per liter) changes. * Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening. * A positive pre-study drug/alcohol screen. *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| GSK2140944 PK parameters following single IV or oral doses of [14C]-GSK2140944 | 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 | 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. |
| Total recovery of radioactivity in urine and feces following separate single IV and oral doses of [14C]-GSK2140944 | 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 | Total recovery of radioactivity in urine and feces is defined as a percentage of total radioactive dose in each interval and cumulatively. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of GSK2140944 after single IV and oral doses as assessed by clinical laboratory tests | Day 1 and Day 8 of each treatment period | clinical laboratory tests includes hematology, clinical chemistry, urinalysis |
| Number of subjects with adverse events (AE) | Up to 7 weeks | — |
| Safety and tolerability of GSK2140944 after single IV and oral doses as assessed by vital signs | Day 1 (Pre dose and 1 hr, 2 hr, 4 hr and 8 hr post dose)and Day 8 of each treatment period | Vital sign measurements to be measurement include systolic and diastolic blood pressure, pulse rate and temperature. |
| Safety and tolerability of GSK2140944 after single IV and oral doses as assessed by electrocardiogram (ECG) | Day 1 (Pre dose and 1 hr, 2 hr, 4 hr and 8 hr post dose)and Day 8 of each treatment period | 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. |
| Safety and tolerability of GSK2140944 after single IV and oral doses as assessed by concomitant medications review | Up to 7 weeks | — |
Countries
United Kingdom
Outcome results
None listed