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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GSK2140944 for Injection and Capsule | Experimental | Each subject will receive a single 1000 milligram (mg) IV dose of GSK2140944 containing [14C]-GSK2140944 of approximately 22.5 microcurie [μCi] (approximately 0.8 megabecquerel [MBq]) of radioactivity given as a 2 hour infusion on Day 1 of treatment period 1 and 2000 mg oral dose of GSK2140944 containing [14C]-GSK2140944 of approximately 45 μCi (approximately 1.7 MBq) of radioactivity on Day 1 of treatment period 2. Each treatment period will be followed with washout of atleast 8 Days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2140944 for Injection | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 concomitant medications review | Up to 7 weeks | |
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Inclusion Criteria:
Exclusion Criteria:
Subjects who have received a total body radiation dose of greater than 5.0 millisievert (upper limit of World Health Organization category II) or exposure to significant radiation (e.g. serial x-ray or CT scans, barium meal etc) in the 12 months prior to this study.
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | London | NW10 7NS | United Kingdom |
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| Label | URL |
|---|---|
| Results for study 115774 can be found on the GSK Clinical Study Register. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 115774 | Annotated Case Report Form | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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|
| GSK2140944 Capsule | Drug | 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. |
|
| 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 |
| 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. | 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. | Day 1 (Pre dose and 1 hr, 2 hr, 4 hr and 8 hr post dose)and Day 8 of each treatment period |
For additional information about this study please refer to the GSK Clinical Study Register |
| 115774 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115774 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115774 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115774 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115774 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115774 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| ID | Term |
|---|---|
| D007239 | Infections |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C000612856 | gepotidacin |
| D007267 | Injections |
| ID | Term |
|---|---|
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
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