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This will be the first time GSK1325756 Solution for Infusion formulation that has been administered to humans. Prior studies have been performed with oral GSK1325756. The primary objectives of this study are to obtain information on the safety, tolerability, and pharmacokinetics (PK) of single and twice daily intravenous (IV) administration of GSK1325756 in healthy subjects. In Part A, single, escalating doses will be given in the same cohort of subjects after a seven day washout. In addition, the study will evaluate the absolute bioavailability of a single dose of the current oral tablet formulation as compared to the IV formulation in Part A. In Part B, twice daily (BID) intravenous dose administration will be given for 5 days (9 total doses) in two separate cohorts of subjects. Data from this study will provide understanding of the safety, tolerability, and PK of intravenously administered GSK1325756 twice daily to guide dose selection in future clinical studies in patients with viral respiratory tract infections
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A (Cohort 1) | Experimental | Approximately 8 subjects (6 Active, 2 Placebo) will be randomized to receive single escalating IV doses i.e.10 milligrams (mg), 25 mg and 100 mg, plus one oral 100 mg dose (on the last occasion) of GSK1325756 or matching placebo, with a 7-days washout between doses. Dose escalations will be based on review of PK and safety data from preceding dose level. The projected doses for each group are subject to modification based upon PK and safety data from preceding cohorts. Pharmacokinetic parameters will be reviewed from at least 4 active subjects from preceding dose before dose escalating to the next dose level. The maximum dose administered will be 100 mg. Additional subjects/Cohorts may be enrolled. |
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| Part B (Cohorts 2 and 3) | Experimental | Approximately 8 subjects (6 Active, 2 Placebo) per cohort will be randomized to receive escalating repeated IV doses of GSK1325756 or matching placebo (Cohort 2: 25 mg, Cohort 3: 50 mg) for 5 days. Repeated (BID) doses of GSK1325756 will begin the morning of Day 1 and continue through the morning of Day 5 (9 total doses). Dose escalations will be based on review of PK and safety data from preceding dose level. The projected doses for each group are subject to modification based upon PK and safety data from preceding cohorts. Pharmacokinetic parameters will be reviewed from at least 4 active subjects from preceding dose before dose escalating to the next dose level. The maximum dose administered will be 50 mg BID. Additional subjects/Cohorts may be enrolled. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK1325756 Solution | Drug | Solution containing 2 mg/mL GSK1325756 in sterile water for injection, to be administered intravenously. |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of subjects with adverse events (AEs) | An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product | Part A and Part B: from Day -1 until 7 to 10 days post-last dose |
| Changes over time in clinical laboratory evaluations from pre-dose values | Clinical laboratory assessments will include hematology, clinical chemistry, urinalysis parameters | Part A and Part B: from Day -1 until 7 to 10 days post-last dose |
| Changes over time in vital signs from pre-dose values | Vital sign measurements will include systolic and diastolic blood pressure and pulse rate | Part A and Part B: from Day -1 until 7 to 10 days post-last dose |
| Changes over time in electrocardiogram (ECG) parameters from pre-dose values | 12-lead ECGs will be obtained at each timepoint | Part A and Part B: from Day -1 until 7 to 10 days post-last dose |
| GSK1325756 PK parameters following single dose administration in Part A and on Day 1 of Part B | PK parameters will include area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time [AUC(0-infinity)], area under the concentration-time curve from time zero (pre-dose) to time t [AUC(0-t)], area under the concentration-time curve from time zero (pre-dose) to 24 hours [AUC(0-24)], maximum observed concentration (Cmax), time to maximum observed concentration (tmax), observed concentration at 24 hours post-dose (C24), terminal half-life (t1/2), time of last measurable concentration (tlast), clearance (CL) and volume of distribution (Vz) | Part A: Pre-dose, 0.5 hour (hr), 1hr (end of infusion/post oral dose), 1.5, 2, 3, 4, 8, 12, 24hrs post-dose in each treatment period. |
| Measure | Description | Time Frame |
|---|---|---|
| GSK1325756 PK parameters following single and repeat IV dose administration to assess dose proportionality | PK parameters will include AUC(0-infinity), AUC(0-t), Cmax, and C24 following single IV dose administration (Part A) and AUC(0-tau), Ctau, and Cmax following repeated IV dose administration (Part B) | Part A: Pre-dose, 0.5hr, 1hr (end of infusion/post oral dose), 1.5, 2, 3, 4, 8, 12, 24hrs post-dose. Part B: Day 1 and Day 5: pre-dose, 0.5, 1hr (end of infusion), 1.5, 2, 3, 4, 8, 12 and (Day 5 only) 24 hrs post-dose. Day 2-4: pre-dose (each dose) |
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Inclusion Criteria:
Exclusion 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 |
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| Label | URL |
|---|---|
| Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. | View source |
| Results for study 201022 can be found on the GSK Clinical Study Register. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 201022 | Dataset Specification | 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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| GSK1325756 Solution Matching Placebo | Drug | Solution containing sterile water for injection matching GSK1325756 solution, to be administered intravenously. |
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| GSK1325756 Tablet | Drug | A white film coated tablet containing 50 mg GSK1325756 to be administered orally. |
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| GSK1325756 Tablet Matching Placebo | Drug | A white film coated tablet matching GSK1325756 tablet, to be administered orally. |
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| GSK1325756 PK parameters following repeat dose administration (Part B, Day 5) | PK parameters will include area under the concentration-time curve from time zero (pre-dose) to the end of the dosing interval [AUC(0-tau)], concentration at the end of the dosing interval (Ctau), Cmax, tmax, t1/2, Volume of distribution at steady-state (Vdss), and oral clearance (CL/F) | Part B: Day 5 at pre-dose, 0.5, 1hr (end of infusion), 1.5, 2, 3, 4, 8, 12 and 24 hrs post-dose |
| GSK1325756 PK parameters following single IV and oral dose administration of a given dose of GSK1325756 (Part A) to determine the absolute bioavailability | PK parameters will include AUC(0-infinity), AUC(0-t), Cmax and tmax | Part A: Pre-dose, 0.5hr, 1hr (end of infusion/post oral dose), 1.5, 2, 3, 4, 8, 12, 24hrs post-dose |
| GSK1325756 accumulation ratio | GSK1325756 AUC(0-tau), Cmax, and Ctau on the last day of dosing will be compared to area under the concentration-time curve from time zero (pre-dose) to 12 hours [AUC(0-12)], Cmax, and observed concentration at 12 hours post-dose (C12) on Day 1 to estimate accumulation ratio | Part A: Pre-dose, 0.5hr, 1hr (end of infusion/post oral dose), 1.5, 2, 3, 4, 8, 12, 24hrs post-dose Part B: Day 1 and Day 5: pre-dose, 0.5, 1hr (end of infusion), 1.5, 2, 3, 4, 8, 12 and (Day 5 only) 24 hrs post-dose. Day 2-4: pre-dose (each dose) |
| GSK1325756 time invariance | GSK1325756 AUC(0-tau) on the last day of dosing in Part B, will be compared to AUC(0-infinity) on Day 1 of Part A to evaluate time invariance | Part A: Pre-dose, 0.5hr, 1hr (end of infusion/post oral dose), 1.5, 2, 3, 4, 8, 12, 24hrs post-dose Part B: Day 1 and Day 5: pre-dose, 0.5, 1hr (end of infusion), 1.5, 2, 3, 4, 8, 12 and (Day 5 only) 24 hrs post-dose. Day 2-4: pre-dose (each dose) |
| GSK1325756 Pre-dose concentrations (C12/Ctau) on Day 2 through 4 | GSK1325756 Pre-dose concentrations on Day 2 through 4 will be used to assess the achievement of steady state of GSK1325756 following repeat administration (Part B) | Part B: Day 2 to Day 4 (pre-dose; each dose) |
| Correlation between PK parameters and various safety parameters, if appropriate | Part A and Part B: from Day -1 until 7 to 10 days post-last dose |
For additional information about this study please refer to the GSK Clinical Study Register |
| 201022 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 201022 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 201022 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 201022 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 201022 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 201022 | Clinical Study Report | 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 |
|---|---|
| C581951 | danirixin |
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