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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01014988




Registration number
NCT01014988
Ethics application status
Date submitted
16/11/2009
Date registered
17/11/2009
Date last updated
28/03/2017

Titles & IDs
Public title
Safety Study to Assess IV Zanamivir for Treatment of Influenza Infection in Patients Who Are in Hospital
Scientific title
An Open-label, Multi-center, Single Arm Study to Evaluate the Safety and Tolerability of Intravenous Zanamivir in the Treatment of Hospitalized Adult, Adolescent and Pediatric Subjects With Confirmed Influenza Infection
Secondary ID [1] 0 0
113678
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Influenza, Human 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - zanamivir aqueous solution

Other: Single Arm - A single arm open-label design has been selected to achieve the primary objective of providing regulatory authorities with safety data on IV zanamivir in an expedited manner. This study design also facilitates the provision of safety data on a real-time basis, if necessary.


Treatment: Drugs: zanamivir aqueous solution
Zanamivir aqueous solution 10mg/mL is a clear, colorless, single use, sterile non-preserved preparation containing 10mg of zanamivir in each milliliter, and made isotonic with sodium chloride. It is presented in 20mL clear glass vials closed with rubber stoppers. Each vial contains 200mg of zanamivir.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Any Adverse Event (AE) Considered to be Related to Study Treatment - An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. All AEs were assesed by the Investigateor as related or not related to the study treatment.
Timepoint [1] 0 0
Up to post-treatment (PT) + 23 days
Primary outcome [2] 0 0
Number of Participants With Any Severe or Grade 3/4 AEs - An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. AEs that occured during the study were evaluated by the Investigator and graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) table for grading the severity of adult and pediatric AEs. Grade 3=severe; Grade 4=potentially life threatening.
Timepoint [2] 0 0
Up to post-treatment (PT) + 23 days
Primary outcome [3] 0 0
Number of Participants With Any Severe or Grade 3/4 Treatment-related AE - An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. AEs that occured during the study were evaluated by the Investigator and graded according to the DAIDS table for grading the severity of adult and pediatric AEs. Grade 3=severe; Grade 4=potentially life threatening. All AEs were assesed by the Investigateor as related or not related to the study treatment.
Timepoint [3] 0 0
Up to post-treatment (PT) + 23 days
Primary outcome [4] 0 0
Number of Participants Who Permanently Discontinued the Study Treatment Due to an AE - An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
Timepoint [4] 0 0
Up to 10 days
Primary outcome [5] 0 0
Number of Participants Who Were Permanently Discontinued From the Study Due to an AE - An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
Timepoint [5] 0 0
Up to post-treatment (PT) + 23 days
Primary outcome [6] 0 0
Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5 - Blood samples for laboratory assessments were collected at Baseline (Day [D] 1), Days 3 and 5, and on post-treatment +2 days (if hospitalized) and post-treatment +23 days. Clinical chemistry parameters included alanine aminotransferase (ALT), direct bilirubin (DB), total bilirubin (TB), and creatinine. The number of participants with values that were high (H)/normal (N)/low (L) relative to the normal range at Baseline (D 1) and D 5 for the indicated clinical chemistry parameters are summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Timepoint [6] 0 0
Baseline (Day 1) and Day 5
Primary outcome [7] 0 0
Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5 - Blood samples for laboratory assessments were collected at Baseline (Day [D] 1), Days 3 and 5, and on post-treatment +2 days (if hospitalized) and post-treatment +23 days. Hematology parameters included hemoglobin, total neutrophils (TN), and white blood cell (WBC) count. The number of participants with values that were high (H)/normal (N)/low (L) relative to the normal range at Baseline (D 1) and D 5 for the indicated hematology parameters are summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Timepoint [7] 0 0
Baseline (Day 1) and Day 5
Primary outcome [8] 0 0
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Toxicities - A toxicity was considered to be TE if it was greater than the Baseline grade, and if it had developed or increased post-Baseline in intensity (and prior to the last dose of investigational product). Clinical chemistry parameters included ALT, TB, and creatinine. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade 3=severe and Grade 4=potentially life threatening. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Timepoint [8] 0 0
Up to post-treatment (PT) + 23 days
Primary outcome [9] 0 0
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities - A toxicity was considered to be TE if it was greater than the Baseline grade, and if it had developed or increased post-Baseline in intensity (and prior to the last dose of investigational product). The hematology parameters included hemoglobin, TN, and WBC count. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade 3=severe and Grade 4=potentially life threatening. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Timepoint [9] 0 0
Up to post-treatment (PT) + 23 days
Primary outcome [10] 0 0
Median Heart Rate at Baseline (Day 1) and Day 5 - Heart rate was measured at Baseline (Day 1); Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. Heart rate was assessed once daily during inpatient or outpatient follow-up visits. Heart rate values at Baseline (Day 1) and Day 5 are summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles).
Timepoint [10] 0 0
Baseline (Day 1) and Day 5
Primary outcome [11] 0 0
Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5 - SBP and DBP were measured at Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. SBP and DBP were assessed once daily during inpatient or outpatient follow-up visits. SBP and DBP values at Baseline (Day 1) and Day 5 are summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles).
Timepoint [11] 0 0
Baseline (Day 1) and Day 5
Primary outcome [12] 0 0
Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5 - TCPO2 is a noninvasive test that directly measures the oxygen level of tissue beneath the skin. Because oxygen is carried to tissues by blood flow in the arteries, TCPO2 is an indirect measure of blood flow. The percent (%) oxygen saturation was measured at Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; and post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. Oxygen saturation was assessed once daily during inpatient follow-up visits. The median oxygen saturation values at Baseline (Day 1) and Day 5 are summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles).
Timepoint [12] 0 0
Baseline (Day 1) and Day 5
Primary outcome [13] 0 0
Median Respiration Rate at Baseline (Day 1) and Day 5 - Respiration rate was measured at Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; and post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. Respiration rate was assessed once daily during inpatient or outpatient follow-up visits. The median respiration rate at Baseline (Day 1) and Day 5 is summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles).
Timepoint [13] 0 0
Baseline (Day 1) and Day 5
Primary outcome [14] 0 0
Median Body Temperature at Baseline (Day 1) and Day 5 - Body temperature was recorded at Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; and post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. Body temperature was recorded once daily during inpatient or outpatient follow-up visits. Median body temperature at Baseline (Day 1) and Day 5 is summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles).
Timepoint [14] 0 0
Baseline (Day 1) and Day 5
Primary outcome [15] 0 0
Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1) - The number of participants with an ECG status of normal and abnormal CS or NCS, as determined by the Investigator, is reported. Normal=all ECG parameters within the accepted normal ranges. Abnormal=ECG findings outside of normal ranges. CS=ECG with a CS abnormality that meets exclusion criteria. NCS=ECG with an abnormality that is not CS nor meets exclusion criteria, per Investigator, based on reasonable standards of clinical judgment. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X in the category titles).
Timepoint [15] 0 0
Baseline (Day 1)
Primary outcome [16] 0 0
Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5 - Twelve-lead ECGs were recorded for the parameters of QTcF and QTcB. The first set of pre-dose ECG values at Baseline (Day 1) and the pre-dose ECG values at Day 5 are presented. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles). "NA" indicates that data are not available/analysis was not performed. Cohort 1 QTcF and QTcB minimum values of 0.0 were data entry errors that could not be addressed after Data Base Freeze.
Timepoint [16] 0 0
Baseline (Day 1) and Day 5
Secondary outcome [1] 0 0
Median Time to Virologic Improvement - Time to virologic improvement is defined as a 2-log drop in viral load or undetectable viral ribonucleic acid (RNA) as measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) from nasopharyngeal samples (PCR positive at Baseline). Only those participants available at the specified time points were analyzed.
Timepoint [1] 0 0
Up to post-treatment (PT) + 23 days
Secondary outcome [2] 0 0
Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points - Change from Baseline in viral load was measured from nasopharyngeal swab samples, as determined by RT-PCR (PCR positive at Baseline). Nasopharyngeal swab samples were collected at Baseline (Day 1); Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10; and, only if the participants had continued symptoms and were hospitalized, post-treatment (PT) samples were collected at +2 days, +5 days, +9 days, +16 days, and +23 days. 'PT +23 days' also comprises viral load values at early study withdrawal. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X in the category titles). "NA" indicates that data are not available/analysis was not performed.
Timepoint [2] 0 0
Baseline (Day 1); Days 2, 3, 4, 5, 7, and 10; and post-treatment +2, +5, +9, +16, +23 days
Secondary outcome [3] 0 0
Mean Viral Susceptibility to Zanamivir at Baseline (Day 1) and All Post-Baseline Visits Collectively - Viral susceptibility to zanamivir at Baseline and at all post-Baseline visits collectively was assessed by neuraminidase (NA) enzyme inhibition assay. The mean IC50 data are summarized by subtype (A/H1N1, A/H3N2, B) and by visit. IC50 is defined as the concentration of zanamvir required to inhibit NA activity by 50%. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). "NA" indicates that data are not available/analysis was not performed. Please note: pediatric data are pending and will be updated when available.
Timepoint [3] 0 0
Baseline and up to post-treatment (PT) + 23 days
Secondary outcome [4] 0 0
Number of Participants With Treatment-emergent (TE) Mutations - Viral RNA isolated from participants at Baseline (Day 1) and post-Baseline visits were sequenced to determine the presence of TE neuraminidase (NA) and hemagglutinin (HA) mutations resulting from selective pressure. A mutation was considered to be TE if it was not present at Baseline and was present in the last post-Baseline sample analyzed.These mutations were classified as either known to confer zanamvir resistance or novel mutations with unknown clinical significance. Please note: pediatric data are pending and will be updated when available.
Timepoint [4] 0 0
Baseline and up to post-treatment (PT) + 23 days
Secondary outcome [5] 0 0
Median Time to Resolution of Individual Vital Signs - Times to return to afebrile status (normal body temperature), normal respiratory status, normal heart rate, and normal systolic blood pressure were assessed. Afebrile status is defined as a temperature <=36.6 axilla, <=37.2 oral, or <=37.7 rectal, core or typanic, degrees Centigrade. A return to normal respiratory status is defined as either: (a) return to pre-morbid oxygen requirement; or (b) return to no need for supplemental oxygen; or (c) respiratory rate <=60, <=40, <=34, <=30, <=24 or <=24 breaths/minute (without supplemental oxygen) for Cohorts 1-6 respectively . A normal HR is defined as <=160, <=150, <=140, <=120, <=100 or <=100 bpm for Cohorts 1-6 respectively, and a normal SBP is defined as >=70, >=74, >=76, >=80, >=90 or >=90 mmHg for Cohorts 1-6 respectively. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X in the category titles).
Timepoint [5] 0 0
Up to post-treatment (PT) + 23 days
Secondary outcome [6] 0 0
Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation - Ventilation status was measured at Baseline (Day 1); Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; and post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. Ventilation status was assessed once daily during inpatient follow-up visits. The number of participants reported for machine-assisted: extracorporeal membrane oxygenation (ECMO), endotracheal mechanical ventilation, and supplemental oxygen delivery (SOD) at "any time (AT) on study" and at Baseline (Day 1) are summarized.
Timepoint [6] 0 0
Up to post-treatment (PT) + 23 days
Secondary outcome [7] 0 0
Duration of Mechanical Ventilation and Supplemental Oxygen Use - Due to the conditional nature of data collection post treatment, the duration of mechanical ventilation and supplemental oxygen use were not determined.
Timepoint [7] 0 0
Up to discharge from the hospital
Secondary outcome [8] 0 0
Median Time to Return to Pre-morbid Functional Status - Time to return to pre-morbid functional status was assessed on a 3-point scale (bed rest, limited ambulation, or unrestricted). Only those participants available at the specified time points were analyzed.
Timepoint [8] 0 0
Up to post-treatment (PT) + 23 days
Secondary outcome [9] 0 0
Number of Participants With the Indicated Mortality Status at Day 14 and Day 28 - The number of participants who died on or before Study Day 14 and Study Day 28 was summarized. Only those participants available at the specified time points were analyzed.
Timepoint [9] 0 0
Day 14 and Day 28
Secondary outcome [10] 0 0
Median Time to Clinical Response (Sustained Resolution) of All Vital Signs (Composite) - Sustained resolution of the following vital signs (composite) was assessed: afebrile status, normal oxygen saturation, normal respiratory status, normal HR, and normal BP. Clinical response is defined as the resolution of at least four of five vital signs within the following resolution criteria, maintained for 24 hours or hospital discharge, whichever occurred first: Temperature in degrees Centigrade (<=36.6 axilla, <=37.2 oral, <=37.7 rectal, core or tympanic); oxygen saturation (>=95%, without supplemental oxygen); respiratory status (return to pre-morbid oxygen requirement, or no need for supplemental oxygen, or respiratory rate <=60, <=40, <=34, <=30, <=24 or <=24 breaths/minute without supplemental oxygen for Cohorts 1-6 respectively); HR (<=160, <=150, <=140, <=120, <=100 or <=100 bpm for Cohorts 1-6 respectively); SBP (>=70, >=74, >=76, >=80, >=90 or >=90 mmHg for Cohorts 1-6 respectively). Only those participants available at the specified time points were analyzed.
Timepoint [10] 0 0
Up to post-treatment (PT) + 23 days
Secondary outcome [11] 0 0
Number of Participants With Any AE Categorized as an Influenza Complication - An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
Timepoint [11] 0 0
Up to post-treatment (PT) + 23 days
Secondary outcome [12] 0 0
Number of Participants Who Used Any Concomitant Antibiotic Medications for Complications of Influenza - Concomitant medications (prescription and non-prescription) were permitted during the course of the study at the Investigator's discretion (except for prohibited medications: during the treatment period with IV zanamivir, other influenza antiviral drugs were not permitted). The number of participants who were treated with antibiotics for influenza complications was summarized.
Timepoint [12] 0 0
Up to post-treatment (PT) + 23 days
Secondary outcome [13] 0 0
Median Duration of Hospitalization and Intensive Care Unit (ICU) Stays - The duration of hospitalization (H) reflects the number of hospitalization days between the date of the first dose of investigational product and the date of discharge. ICU stay includes total duration in ICU and may include days in ICU before entry into the study. For participants with a missing discharge date who were not discharged at the end of the study, the date of discharge was imputed to the last follow-up visit (post-treatment +23 days). Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Timepoint [13] 0 0
Up to discharge from hospital
Secondary outcome [14] 0 0
Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion - The Cmax of zanamivir was evaluated at the end of infusion. Serial blood samples for pharmacokinetic (PK) analysis were collected if possible in conjunction with the initial dose on Day 1 (5-7 serial samples) and over a dosing interval during repeat dosing on Days 3, 4, or 5 (5 serial samples). PK data for all participants with available blood samples were analyzed. PK data for those participants who were neither on extracorporeal membrane oxygenation (ECMO) nor on continuous renal replacement therapy (CRRT), who were with CLcr >=80 mL/minutes (>=80mL/minute/1.73m^2 for cohorts 1-4) and who received an initial dose (ID) and a maintenance dose (MD) of 14 mg/kg (6 months to <6 years of age), 12 mg/kg, not to exceed 600 mg (6 to <18 years of age) or 600 mg zanamivir (>=18 years of age) (represented by n=X in the category titles) were summarized. "NA" indicates that data are not available/analysis was not performed.
Timepoint [14] 0 0
Day 1 and Days 3, 4, or 5
Secondary outcome [15] 0 0
Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir - The AUC(0-tau) during the repeat dose interval and AUC(0-inf) for the initial dose were evaluated. Serial blood samples for PK analysis were collected if possible in conjunction with the initial dose on Day 1 (5-7 serial samples) and over a dosing interval during repeat dosing on Days 3, 4, or 5 (5 serial samples). PK data for all participants with available blood samples were analyzed. PK data for those participants with a CLcr >=80 mL/minutes (>=80 mL/minute/1.73m^2 for cohorts 1-4) and who received an ID and a MD of 14 mg/kg (6 months to <6 years of age), 12 mg/kg, not to exceed 600 mg (6 to <18 years of age) or 600 mg zanamivir (>=18 years of age) (represented by n=X in the category titles) were summarized. "NA" indicates that data are not available/analysis was not performed.
Timepoint [15] 0 0
Day 1 and Days 3, 4, or 5
Secondary outcome [16] 0 0
Geometric Mean Terminal Half Life (t1/2) of Zanamivir - The t1/2 of zanamivir was evaluated. Terminal half life is defined as the time it takes for a substance to lose half of its pharmacologic, physiologic, or radiologic activity. Serial blood samples for PK analysis were collected if possible in conjunction with the initial dose on Day 1 (5-7 serial samples) and over a dosing interval during repeat dosing on Day 3, 4, or 5 (5 serial samples). PK data for all participants with available blood samples were analyzed. PK data for those participants with a CLcr>=80 mL/minutes (>=80 mL/minute/1.73m^2 for cohorts 1-4) and who received an ID and a MD of 14 mg/kg (6 months to <6 years of age), 12 mg/kg, not to exceed 600 mg (6 to <18 years of age) or 600 mg zanamivir (>=18 years of age) (represented by n=X in the category titles) were summarized. "NA" indicates that data are not available/analysis was not performed.
Timepoint [16] 0 0
Day 1 and Days 3, 4, or 5
Secondary outcome [17] 0 0
Geometric Mean Serum Clearance of Zanamivir - The serum clearance of zanamivir was evaluated. Clearance is defined as the volume of zanamivir per unit time eliminated from serum. Serial blood samples for PK analysis were collected if possible in conjunction with the initial dose on Day 1 (5-7 serial samples) and over a dosing interval during repeat dosing on Days 3, 4, or 5 (5 serial samples). PK data for all participants with available blood samples were analyzed. PK data for those participants with a CLcr >=80 mL/minutes (>=80 mL/minute/1.73m^2 for cohorts 1-4) and who received an ID and a MD 14 mg/kg (6 months to <6 years of age), 12 mg/kg, not to exceed 600 mg (6 to <18 years of age) or 600 mg zanamivir (>=18 years of age) (represented by n=X in the category titles) were summarized. "NA" indicates that data are not available/analysis was not performed.
Timepoint [17] 0 0
Day 1 and Days 3, 4, or 5
Secondary outcome [18] 0 0
Geometric Mean Volume of Distribution (Vd) of Zanamivir - The Vd of zanamivir was evaluated. Volume of distribution is defined as the apparent volume in which zanamivir is distributed. Serial blood samples for PK analysis were collected if possible in conjunction with the initial dose on Day 1 (5-7 serial samples) and over a dosing interval during repeat dosing on Days 3, 4, or 5 (5 serial samples). PK data for all participants with available blood samples were analyzed. PK data for those participants with a CLcr >= 80 mL/minutes (>=80 mL/minute/1.73m^2 for cohorts 1-4) and who received an ID and a MD of 14 mg/kg (6 months to <6 years of age), 12 mg/kg, not to exceed 600 mg (6 to <18 years of age) or 600 mg zanamivir (>=18 years of age) (represented by n=X in the category titles) were summarized. "NA" indicates that data are not available/analysis was not performed.
Timepoint [18] 0 0
Day 1 and Days 3, 4, or 5

Eligibility
Key inclusion criteria
- Male or female aged greater than or equal to 6 months of age; a female is eligible to
enter and participate in the study if she is:

1. of non-childbearing potential (i.e., physiologically incapable of becoming
pregnant, including any female who is post-menopausal); or,

2. of child-bearing potential, has a negative pregnancy test at Baseline, and agrees
to one of the following methods for avoidance of pregnancy during the study and
until the Post-Treatment +23 Days Follow-up Assessment:

- Abstinence; or,

- Oral contraceptive, either combined or progestogen alone; or,

- Injectable progestogen; or,

- Implants of levonorgestrel; or,

- Estrogenic vaginal ring; or,

- Percutaneous contraceptive patches; or

- Intrauterine device (IUD) or intrauterine system (IUS) showing that the expected
failure rate is less than 1% per year as stated in the IUD or IUS Product Label; or,

- Has a male partner who is sterilized; or,

- Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps)
with a vaginal spermicidal agent (foam/gel/film/cream/suppository).

- Subjects who have confirmed influenza as determined by a positive result in a rapid
test for influenza A or influenza B, or a laboratory test for influenza including
influenza virus antigen test, virus culture or RT-PCR test. Subjects with negative
rapid test result suspected of having influenza can be enrolled following confirmatory
testing by RT-PCR, antigen test or culture.

- Hospitalized subjects with symptomatic influenza

- Subjects who are able to receive their first dose of study medication within seven
days of experiencing influenza-like symptoms.

- Subjects willing and able to adhere to the procedures stated in the protocol.

- Subjects/legally acceptable representative (LAR) of minors and unconscious adults
willing and able to give written informed consent to participate in the study (or
included as permitted by local regulatory authorities, IRBs/IECs or local laws).

- French subjects: In France, a subject will be eligible for inclusion in this study
only if either affiliated to or a beneficiary of a social security category.

- UK subjects and subjects in Spain: Subjects should be in a high dependency or
intensive care setting at the time of enrollment and either have severe and
progressive illness on approved influenza antivirals, or are considered unsuitable for
treatment with approved influenza antivirals.

- Subjects who have severe or progressive influenza illness on approved (fully licensed)
influenza antivirals, or who are considered unsuitable or inappropriate for treatment
with approved influenza antivirals, or who in the opinion of the investigator may
benefit from IV zanamivir therapy.
Minimum age
6 Months
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Subjects who, in the opinion of the investigator, are not likely to survive the next
48 hours beyond Baseline.

- Subjects who require concurrent therapy with another influenza antiviral drug.

- Subjects who have participated in a study using an investigational influenza antiviral
drug within 30 days prior to Baseline.

- Subjects who are known or suspected to be hypersensitive to any component of the study
medication.

- Subjects who meet the following criteria at Baseline:

- ALT greater than or equal to 3xULN and bilirubin greater than or equal to 2xULN or ALT
greater than or equal to 5xULN

- History of cardiac disease or clinically significant arrhythmia (either on ECG or by
history) which, in the opinion of the Investigator, will interfere with the safety of
the individual subject.

- Child in care (CiC) as defined below:

A child who has been placed under the control or protection of an agency, organization,
institution or entity by the courts, the government or a government body, acting in
accordance with powers conferred on them by law or regulation.

The definition of a CiC can include a child cared for by foster parents or living in a care
home or institution, provided that the arrangement falls within the definition above. The
definition of a CiC does not include a child who is adopted or has an appointed legal
guardian.

- French subjects: the French subject has participated in any study using an
investigational drug during the previous 30 days.

- Females who are pregnant (positive urine or serum pregnancy test at Baseline) or are
breastfeeding.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Garran
Recruitment hospital [2] 0 0
GSK Investigational Site - Chermside
Recruitment hospital [3] 0 0
GSK Investigational Site - Herston
Recruitment hospital [4] 0 0
GSK Investigational Site - Adelaide
Recruitment hospital [5] 0 0
GSK Investigational Site - Bedford Park
Recruitment hospital [6] 0 0
GSK Investigational Site - Heidelberg
Recruitment hospital [7] 0 0
GSK Investigational Site - Perth
Recruitment hospital [8] 0 0
GSK Investigational Site - Subiaco
Recruitment postcode(s) [1] 0 0
2606 - Garran
Recruitment postcode(s) [2] 0 0
4032 - Chermside
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
5043 - Bedford Park
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment postcode(s) [7] 0 0
6000 - Perth
Recruitment postcode(s) [8] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
District of Columbia
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Georgia
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Kansas
Country [11] 0 0
United States of America
State/province [11] 0 0
Kentucky
Country [12] 0 0
United States of America
State/province [12] 0 0
Louisiana
Country [13] 0 0
United States of America
State/province [13] 0 0
Massachusetts
Country [14] 0 0
United States of America
State/province [14] 0 0
Minnesota
Country [15] 0 0
United States of America
State/province [15] 0 0
Missouri
Country [16] 0 0
United States of America
State/province [16] 0 0
Montana
Country [17] 0 0
United States of America
State/province [17] 0 0
New Jersey
Country [18] 0 0
United States of America
State/province [18] 0 0
New York
Country [19] 0 0
United States of America
State/province [19] 0 0
North Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
Ohio
Country [21] 0 0
United States of America
State/province [21] 0 0
Oregon
Country [22] 0 0
United States of America
State/province [22] 0 0
Pennsylvania
Country [23] 0 0
United States of America
State/province [23] 0 0
Tennessee
Country [24] 0 0
United States of America
State/province [24] 0 0
Texas
Country [25] 0 0
United States of America
State/province [25] 0 0
Utah
Country [26] 0 0
United States of America
State/province [26] 0 0
Virginia
Country [27] 0 0
United States of America
State/province [27] 0 0
Wisconsin
Country [28] 0 0
Brazil
State/province [28] 0 0
São Paulo
Country [29] 0 0
Brazil
State/province [29] 0 0
Rio de Janeiro
Country [30] 0 0
Canada
State/province [30] 0 0
Manitoba
Country [31] 0 0
Canada
State/province [31] 0 0
Nova Scotia
Country [32] 0 0
Canada
State/province [32] 0 0
Ontario
Country [33] 0 0
Canada
State/province [33] 0 0
Quebec
Country [34] 0 0
France
State/province [34] 0 0
Bron cedex
Country [35] 0 0
France
State/province [35] 0 0
Grenoble cedex 9
Country [36] 0 0
France
State/province [36] 0 0
Limoges cedex
Country [37] 0 0
France
State/province [37] 0 0
Nancy cedex
Country [38] 0 0
France
State/province [38] 0 0
Nice
Country [39] 0 0
France
State/province [39] 0 0
Nîmes cedex 9
Country [40] 0 0
France
State/province [40] 0 0
Orléans cedex 2
Country [41] 0 0
France
State/province [41] 0 0
Paris cedex 14
Country [42] 0 0
France
State/province [42] 0 0
Paris
Country [43] 0 0
France
State/province [43] 0 0
Tours cedex 9
Country [44] 0 0
Hong Kong
State/province [44] 0 0
Shatin
Country [45] 0 0
Japan
State/province [45] 0 0
Fukuoka
Country [46] 0 0
Japan
State/province [46] 0 0
Hokkaido
Country [47] 0 0
Japan
State/province [47] 0 0
Kanagawa
Country [48] 0 0
Japan
State/province [48] 0 0
Osaka
Country [49] 0 0
Japan
State/province [49] 0 0
Yamanashi
Country [50] 0 0
Norway
State/province [50] 0 0
Bergen
Country [51] 0 0
Norway
State/province [51] 0 0
Trondheim
Country [52] 0 0
Russian Federation
State/province [52] 0 0
Ekaterinburg
Country [53] 0 0
Russian Federation
State/province [53] 0 0
Smolensk
Country [54] 0 0
South Africa
State/province [54] 0 0
Mpumalanga
Country [55] 0 0
South Africa
State/province [55] 0 0
Bellville
Country [56] 0 0
South Africa
State/province [56] 0 0
Observatory
Country [57] 0 0
South Africa
State/province [57] 0 0
Panorama
Country [58] 0 0
South Africa
State/province [58] 0 0
Rondebosch
Country [59] 0 0
South Africa
State/province [59] 0 0
Tygerberg
Country [60] 0 0
South Africa
State/province [60] 0 0
Worcester
Country [61] 0 0
Spain
State/province [61] 0 0
(Móstoles) Madrid
Country [62] 0 0
Spain
State/province [62] 0 0
Badalona
Country [63] 0 0
Spain
State/province [63] 0 0
Barcelona
Country [64] 0 0
Spain
State/province [64] 0 0
Getafe/Madrid
Country [65] 0 0
Spain
State/province [65] 0 0
L'Hospitalet de Llobregat
Country [66] 0 0
Spain
State/province [66] 0 0
Madrid
Country [67] 0 0
Thailand
State/province [67] 0 0
Bangkok
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Lanarkshire
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Merseyside
Country [70] 0 0
United Kingdom
State/province [70] 0 0
West Lothian
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Bristol
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Cardiff
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Leeds
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Leicester
Country [75] 0 0
United Kingdom
State/province [75] 0 0
London
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Oxford
Country [77] 0 0
United Kingdom
State/province [77] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine whether zanamivir aqueous solution given by
intravenous injection is safe in treating hospitalized patients with confirmed influenza
infection. A single arm open-label design has been selected to achieve the primary objective
of providing regulatory authorities with safety data on IV zanamivir.
Trial website
https://clinicaltrials.gov/show/NCT01014988
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications