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This study will be conducted in three parts (Part 1, Part 2 and Part 3). Part 1 of this study will evaluate the relative bioavailability of a single dose of GSK2140944 tablet formulation compared to the reference capsule formulation under fasted conditions. The effect of food on the pharmacokinetics (PK) of a single dose of the tablet formulation will also be assessed. Part 2 will evaluate the effect of repeat doses of itraconazole on the pharmacokinetics of GSK2140944 following a single dose. A decision will be made whether to use the current capsule formulation or the new tablet formulation in Part 2 based upon the safety and PK data obtained from Part 1. Part 3 is conditionally based upon progression of the tablet formulation from Part 1 and will evaluate the effect of food on the safety, tolerability, and pharmacokinetics of the tablet formulation following multiple doses in elderly healthy subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1 | Experimental | Subjects will receive either GSK2140944 1500 mg (500 mg x 3) capsules under fasted conditions or GSK2140944 1500 mg (750 mg x 2) tablets under fasted conditions or GSK2140944 1500 mg (750 mg x 2) tablets under fed conditions as per the randomization schedule in each of the three periods with a washout period of at least 3 days between the doses. There will also be a follow-up visit within 5-7 days after the last dose of study drug. |
|
| Part 2 | Experimental | Subjects will receive a single dose of GSK2140944 1500 mg (tablet or capsule) on Day 1 followed by a repeat dose of Itraconazole 200 mg once daily for 6 days from Day 4 to Day 9. On Day 7, subjects will receive a single dose of GSK2140944 1500 mg (tablet or capsule) one hour after the dose of Itraconazole. There will also be a follow-up visit within 5-7 days after the last dose of study drug. |
|
| Part 3 | Experimental | Subjects in Group 1 will receive GSK2140944 1500 mg (750 mg x 2) tablets twice daily from Day 1 to Day 5 under fasting and fed conditions in Period I and Period II, respectively. Subjects in Group 2 will receive GSK2140944 1500 mg (750 mg x 2) tablets twice daily from Day 1 to Day 5 under fed and fasting conditions in Period I and Period II, respectively. There will be a washout of at least 7 days between the periods. Subjects will have a follow up visit 5-7 days after the last dose of study drug in both the groups. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2140944 capsule | Drug | Immediate release capsule containing GSK2140944 and inactive formulation excipients with a unit dose strength of 500 mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Composite of PK parameters following GSK2140944 administration in fasted and fed state | PK parameters will include area under the concentration-time curve (AUC) from time zero (pre-dose) extrapolated to infinite time AUC(0-infinity), AUC from time zero to last quantifiable concentration AUC(0-t), relative bioavailability of drug (Frel), maximum observed concentration (Cmax), time of occurrence of Cmax (tmax), lag time before observation of drug concentration (tlag) and terminal phase half-life (t1/2) in the fasted state; AUC(0-infinity), AUC(0-t), tmax, tlag and Cmax after moderate fat meal. | Day 1 (Pre-dose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, and at 48h) |
| Part 2: Composite of PK parameters of GSK2140944 following repeat oral dosing of itraconazole | PK parameters will include AUC(0-infinity), AUC(0-t), tmax, tlag and Cmax of GSK2140944. | Day 1 and Day 7 (Predose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, and 48h post dose and also at 60h and 72h post dose on Day 7 |
| Part 3: Safety and tolerability of GSK2140944 as assessed by adverse events (AEs) | Approximately 8 weeks | |
| Part 3: Safety and tolerability of GSK2140944 as assessed by review of concomitant medications | Approximately 8 weeks | |
| Part 3: Safety and tolerability of GSK2140944 by laboratory assessments | Laboratory assessments will include hematology, clinical chemistry, urinalysis parameters | Approximately 8 weeks |
| Part 3: Safety and tolerability of GSK2140944 as assessed by 12-lead electrocardiograms (ECGs) | All 12-lead ECGs will be obtained after the subject has rested in a supine position for at least 10 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Safety and tolerability of GSK2140944 as assessed by AEs | Approximately 7 weeks | |
| Part 1: Safety and tolerability of GSK2140944 as assessed by review of concomitant medications | Approximately 7 weeks |
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Inclusion Criteria:
Exclusion Criteria:
Criteria Based Upon Medical Histories
Criteria Based Upon Diagnostic Assessments
Other Criteria
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Overland Park | Kansas | 66211 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35769034 | Derived | Tiffany C, Dumont EF, Hossain M, Srinivasan M, Swift B. Pharmacokinetics, safety, and tolerability of gepotidacin administered as single or repeat ascending doses, in healthy adults and elderly subjects. Clin Transl Sci. 2022 Sep;15(9):2251-2264. doi: 10.1111/cts.13359. Epub 2022 Jul 13. |
| Label | URL |
|---|---|
| Results for study 117349 can be found on the GSK Clinical Study Register. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 117349 | Informed Consent 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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| ID | Term |
|---|---|
| D001424 | Bacterial Infections |
| ID | Term |
|---|---|
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C000612856 | gepotidacin |
| D017964 | Itraconazole |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| GSK2140944 tablet | Drug | Immediate release tablet containing GSK2140944 and inactive formulation excipients with a unit dose strength of 750 mg |
|
| Itraconazole capsule | Drug | Capsule containing Itraconazole with a unit dose strength of 100 mg |
|
| Approximately 8 weeks |
| Part 3: Safety and tolerability of GSK2140944 as assessed by vital signs | Vital signs will be measured for subjects in supine position and will include systolic and diastolic blood pressure, pulse rate and temperature | Approximately 8 weeks |
| Part 1: Safety and tolerability of GSK2140944 by laboratory assessments | Laboratory assessments will include hematology, clinical chemistry, urinalysis parameters | Approximately 7 weeks |
| Part 1: Safety and tolerability of GSK2140944 as assessed by 12-lead ECGs | All 12-lead ECGs will be obtained after the subject has rested in a supine position for at least 10 minutes | Approximately 7 weeks |
| Part 1: Safety and tolerability of GSK2140944 as assessed by vital signs | Vital signs will be measured for subjects in supine position and will include systolic and diastolic blood pressure, pulse rate and temperature | Approximately 7 weeks |
| Part 2: Safety and tolerability of GSK2140944 as assessed by AEs | Approximately 6 weeks |
| Part 2: Safety and tolerability of GSK2140944 by laboratory assessments | Laboratory assessments will include hematology, clinical chemistry, urinalysis parameters | Approximately 6 weeks |
| Part 2: Safety and tolerability of GSK2140944 as assessed by 12-lead ECGs | All 12-lead ECGs will be obtained after the subject has rested in a supine position for at least 10 minutes | Approximately 6 weeks |
| Part 2: Safety and tolerability of GSK2140944 as assessed by vital signs | Vital signs will be measured for subjects in supine position and will include systolic and diastolic blood pressure, pulse rate and temperature | Approximately 6 weeks |
| Part 3: Composite of PK parameters of GSK2140944 following repeat oral dosing of GSK2140944 | PK parameters will include AUC over the dosing interval (0-tau), tmax, tlag, t1/2, pre-dose (trough) concentration at the end of the dosing interval (Ctau) and Cmax of GSK2140944 | Day 3 and Day 4 (Pre-dose), Day 5 (Predose, 0.25h, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, and at 48h) |
For additional information about this study please refer to the GSK Clinical Study Register |
| 117349 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 117349 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 117349 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 117349 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 117349 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 117349 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| D010879 |
| Piperazines |