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Zanamivir is a potent and highly selective inhibitor of the influenza virus neuraminidase. Intravenous (IV) zanamivir is being developed for treatment of hospitalized patients with influenza, especially for those patients who may be in greatest need of parenteral influenza antiviral agents. This study is a pharmacokinetic (PK) study to evaluate the safety/tolerability and pharmacokinetic profiles of IV zanamivir 300 milligrams (mg) and 600 mg in Chinese healthy subjects. Subjects will be randomized to receive either 300 mg or 600 mg IV zanamivir as a single dose followed by repeated dose every 12 hours (h) for 5 days. Subjects will be contacted or will return to study center for a follow-up visit, 7 days after the last dose or withdrawal from the study. Total number of subjects planned for enrollment will be 24 such that approximately 10 subjects complete dosing and critical assessments in each dose cohort. The total duration of the study will be approximately 6 weeks from screening to follow-up.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Zanamivir 300 mg | Experimental | Subjects will receive a single dose of IV zanamivir 300 mg on Day 1 morning. The repeat dose session will begin on Day 3 evening. Subjects will receive IV zanamivir 300 mg every 12 hours for 5 days. Each dose will be administrated intravenously at a constant rate over 30 minutes (500 milliliter per hour [mL/hr]). |
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| Zanamivir 600 mg | Experimental | Subjects will receive a single dose of IV zanamivir 600 mg on Day 1 morning. The repeat dose session will begin on Day 3 evening. Subjects will be receive IV zanamivir 600 mg every 12 hours for 5 days. Each dose will be administrated intravenously at a constant rate over 30 minutes (500 mL/hr). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Zanamivir | Drug | Zanamivir will be supplied as 10 mg/mL sterile clear, colorless, aqueous solution in 20 mL clear glass vials, each containing 200 mg zanamivir. Intravenous solutions will be prepared with normal saline. |
| Measure | Description | Time Frame |
|---|---|---|
| Composite of PK parameters of zanamivir following single dose administration | PK parameter assessed following single dose administration include the observed maximum serum drug concentration (Cmax), time to reach Cmax (tmax), elimination half-time (t1/2), area under the concentration-time curve from administration extrapolated to the last time of quantifiable concentration (AUC [0-t]), area under the concentration-time curve from administration extrapolated to 12 hours of quantifiable concentration (AUC [0-12]), area under the concentration-time curve from time zero extrapolated to infinite time (AUC [0-infinity]), clearance (CL) and volume of distribution after intravenous administration (Vz). | Day 1: Pre-dose and 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h and 24 h post-dose |
| Composite of PK parameters of zanamivir following repeat dose administration | PK parameter assessed following repeat dose administration include Cmax, pre-dose trough concentration (Ctau), tmax, t1/2, AUC (0-t), area under the concentration-time curve during steady state (AUC [0-tau]), CL, Vz, volume of distribution after intravenous administration at steady state (Vss), observed accumulation ratios (Ro) and time invariance ratio (Rs). | Day 8: Pre-dose and 0.25 h, 0.5 h, 0.75 h, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h and 24 h post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Safety as assessed by the number of subjects with adverse events (AEs) | AEs will be collected from the start of study treatment and until the follow-up contact. | Up to Day 15 |
| Composite of clinical laboratory assessments as a measure of safety |
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Inclusion Criteria:
Exclusion Criteria:
Criteria Based Upon Diagnostic Assessments-
Estimated creatinine clearance rate (eCCr) = (140 - Age) x Mass (in Kg) x Constant/Serum Creatinine micromole per liter (μmol/L), where constant is 1.23 for men and 1.04 for women.
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 | Shanghai | 200030 | China |
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| Label | URL |
|---|---|
| Results for study 117104 can be found on the GSK Clinical Study Register. | View source |
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| ID | Term |
|---|---|
| D007251 | Influenza, Human |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D009976 | Orthomyxoviridae Infections |
| D012327 | RNA Virus Infections |
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| ID | Term |
|---|---|
| D053243 | Zanamivir |
| ID | Term |
|---|---|
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D012794 | Sialic Acids |
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Absolute values and change over time from pre-dose values of hematology and clinical chemistry parameters will be assessed
| Up to Day 9 |
| Absolute values and change over time from pre-dose values of blood pressure as a measure of safety | Up to Day 9 |
| Absolute values and change over time from pre-dose values of pulse rate as a measure of safety | Up to Day 9 |
| Absolute values and change over time from pre-dose values of respiratory rate as a measure of safety | Up to Day 9 |
| Absolute values and change over time from pre-dose values of temperature as a safety measure | Up to Day 9 |
| Absolute values and change over time from pre-dose values of electrocardiogram (ECG) parameters | A 12-lead ECG will be obtained at each time point during the study and will be evaluated for safety by a qualified physician. | Up to Day 9 |
| D014777 | Virus Diseases |
| D012140 | Respiratory Tract Diseases |
| D009438 |
| Neuraminic Acids |
| D013400 | Sugar Acids |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D006880 | Hydroxy Acids |
| D011714 | Pyrans |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D000606 | Amino Sugars |
| D002241 | Carbohydrates |