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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/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
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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
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Secondary ID [1]
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113678
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Influenza, Human
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Condition category
Condition code
Intervention/exposure
Study type
Interventional
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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.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Participants With Any Adverse Event (AE) Considered to be Related to Study Treatment
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Assessment method [1]
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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.
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Timepoint [1]
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Up to post-treatment (PT) + 23 days
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Primary outcome [2]
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Number of Participants With Any Severe or Grade 3/4 AEs
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Assessment method [2]
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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.
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Timepoint [2]
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Up to post-treatment (PT) + 23 days
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Primary outcome [3]
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Number of Participants With Any Severe or Grade 3/4 Treatment-related AE
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Assessment method [3]
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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.
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Timepoint [3]
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Up to post-treatment (PT) + 23 days
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Primary outcome [4]
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Number of Participants Who Permanently Discontinued the Study Treatment Due to an AE
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Assessment method [4]
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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.
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Timepoint [4]
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Up to 10 days
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Primary outcome [5]
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Number of Participants Who Were Permanently Discontinued From the Study Due to an AE
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Assessment method [5]
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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.
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Timepoint [5]
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Up to post-treatment (PT) + 23 days
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Primary outcome [6]
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Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5
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Assessment method [6]
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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).
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Timepoint [6]
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Baseline (Day 1) and Day 5
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Primary outcome [7]
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Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5
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Assessment method [7]
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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).
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Timepoint [7]
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Baseline (Day 1) and Day 5
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Primary outcome [8]
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Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Toxicities
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Assessment method [8]
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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).
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Timepoint [8]
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Up to post-treatment (PT) + 23 days
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Primary outcome [9]
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Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities
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Assessment method [9]
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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).
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Timepoint [9]
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Up to post-treatment (PT) + 23 days
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Primary outcome [10]
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Median Heart Rate at Baseline (Day 1) and Day 5
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Assessment method [10]
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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).
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Timepoint [10]
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Baseline (Day 1) and Day 5
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Primary outcome [11]
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Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5
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Assessment method [11]
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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).
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Timepoint [11]
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Baseline (Day 1) and Day 5
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Primary outcome [12]
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Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5
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Assessment method [12]
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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).
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Timepoint [12]
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Baseline (Day 1) and Day 5
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Primary outcome [13]
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Median Respiration Rate at Baseline (Day 1) and Day 5
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Assessment method [13]
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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).
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Timepoint [13]
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Baseline (Day 1) and Day 5
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Primary outcome [14]
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Median Body Temperature at Baseline (Day 1) and Day 5
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Assessment method [14]
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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).
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Timepoint [14]
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Baseline (Day 1) and Day 5
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Primary outcome [15]
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Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1)
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Assessment method [15]
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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).
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Timepoint [15]
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Baseline (Day 1)
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Primary outcome [16]
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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
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Assessment method [16]
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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.
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Timepoint [16]
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Baseline (Day 1) and Day 5
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Secondary outcome [1]
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Median Time to Virologic Improvement
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Assessment method [1]
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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.
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Timepoint [1]
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Up to post-treatment (PT) + 23 days
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Secondary outcome [2]
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Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points
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Assessment method [2]
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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.
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Timepoint [2]
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Baseline (Day 1); Days 2, 3, 4, 5, 7, and 10; and post-treatment +2, +5, +9, +16, +23 days
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Secondary outcome [3]
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Mean Viral Susceptibility to Zanamivir at Baseline (Day 1) and All Post-Baseline Visits Collectively
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Assessment method [3]
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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.
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Timepoint [3]
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Baseline and up to post-treatment (PT) + 23 days
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Secondary outcome [4]
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Number of Participants With Treatment-emergent (TE) Mutations
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Assessment method [4]
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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.
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Timepoint [4]
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Baseline and up to post-treatment (PT) + 23 days
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Secondary outcome [5]
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Median Time to Resolution of Individual Vital Signs
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Assessment method [5]
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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).
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Timepoint [5]
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Up to post-treatment (PT) + 23 days
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Secondary outcome [6]
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Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation
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Assessment method [6]
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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.
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Timepoint [6]
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0
Up to post-treatment (PT) + 23 days
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Secondary outcome [7]
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Duration of Mechanical Ventilation and Supplemental Oxygen Use
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Assessment method [7]
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Due to the conditional nature of data collection post treatment, the duration of mechanical ventilation and supplemental oxygen use were not determined.
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Timepoint [7]
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Up to discharge from the hospital
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Secondary outcome [8]
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Median Time to Return to Pre-morbid Functional Status
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Assessment method [8]
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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.
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Timepoint [8]
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Up to post-treatment (PT) + 23 days
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Secondary outcome [9]
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Number of Participants With the Indicated Mortality Status at Day 14 and Day 28
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Assessment method [9]
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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.
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Timepoint [9]
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Day 14 and Day 28
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Secondary outcome [10]
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Median Time to Clinical Response (Sustained Resolution) of All Vital Signs (Composite)
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Assessment method [10]
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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.
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Timepoint [10]
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0
Up to post-treatment (PT) + 23 days
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Secondary outcome [11]
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Number of Participants With Any AE Categorized as an Influenza Complication
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Assessment method [11]
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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.
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Timepoint [11]
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Up to post-treatment (PT) + 23 days
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Secondary outcome [12]
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Number of Participants Who Used Any Concomitant Antibiotic Medications for Complications of Influenza
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Assessment method [12]
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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.
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Timepoint [12]
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0
Up to post-treatment (PT) + 23 days
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Secondary outcome [13]
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Median Duration of Hospitalization and Intensive Care Unit (ICU) Stays
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Assessment method [13]
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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).
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Timepoint [13]
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Up to discharge from hospital
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Secondary outcome [14]
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Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion
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Assessment method [14]
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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.
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Timepoint [14]
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0
Day 1 and Days 3, 4, or 5
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Secondary outcome [15]
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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
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Assessment method [15]
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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.
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Timepoint [15]
0
0
Day 1 and Days 3, 4, or 5
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Secondary outcome [16]
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Geometric Mean Terminal Half Life (t1/2) of Zanamivir
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Assessment method [16]
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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.
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Timepoint [16]
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0
Day 1 and Days 3, 4, or 5
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Secondary outcome [17]
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0
Geometric Mean Serum Clearance of Zanamivir
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Assessment method [17]
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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.
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Timepoint [17]
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0
Day 1 and Days 3, 4, or 5
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Secondary outcome [18]
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Geometric Mean Volume of Distribution (Vd) of Zanamivir
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Assessment method [18]
0
0
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.
Query!
Timepoint [18]
0
0
Day 1 and Days 3, 4, or 5
Query!
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.
Query!
Minimum age
6
Months
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Query!
Maximum age
No limit
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Query!
Sex
Both males and females
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Can healthy volunteers participate?
No
Query!
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.
Query!
Study design
Purpose of the study
Treatment
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Allocation to intervention
N/A
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/11/2009
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
1/02/2015
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Sample size
Target
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Accrual to date
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Final
202
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Recruitment in Australia
Recruitment state(s)
ACT,QLD,SA,VIC,WA
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Recruitment hospital [1]
0
0
GSK Investigational Site - Garran
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Recruitment hospital [2]
0
0
GSK Investigational Site - Chermside
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Recruitment hospital [3]
0
0
GSK Investigational Site - Herston
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Recruitment hospital [4]
0
0
GSK Investigational Site - Adelaide
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Recruitment hospital [5]
0
0
GSK Investigational Site - Bedford Park
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Recruitment hospital [6]
0
0
GSK Investigational Site - Heidelberg
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Recruitment hospital [7]
0
0
GSK Investigational Site - Perth
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Recruitment hospital [8]
0
0
GSK Investigational Site - Subiaco
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Recruitment postcode(s) [1]
0
0
2606 - Garran
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Recruitment postcode(s) [2]
0
0
4032 - Chermside
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Recruitment postcode(s) [3]
0
0
4029 - Herston
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Recruitment postcode(s) [4]
0
0
5000 - Adelaide
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Recruitment postcode(s) [5]
0
0
5043 - Bedford Park
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Recruitment postcode(s) [6]
0
0
3084 - Heidelberg
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Recruitment postcode(s) [7]
0
0
6000 - Perth
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Recruitment postcode(s) [8]
0
0
6008 - Subiaco
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Recruitment outside Australia
Country [1]
0
0
United States of America
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State/province [1]
0
0
Alabama
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Country [2]
0
0
United States of America
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State/province [2]
0
0
Arizona
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Country [3]
0
0
United States of America
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State/province [3]
0
0
Arkansas
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0
0
United States of America
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State/province [4]
0
0
California
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Country [5]
0
0
United States of America
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State/province [5]
0
0
Connecticut
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0
0
United States of America
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State/province [6]
0
0
District of Columbia
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Country [7]
0
0
United States of America
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State/province [7]
0
0
Florida
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Country [8]
0
0
United States of America
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State/province [8]
0
0
Georgia
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Country [9]
0
0
United States of America
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State/province [9]
0
0
Indiana
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Country [10]
0
0
United States of America
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State/province [10]
0
0
Kansas
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Country [11]
0
0
United States of America
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State/province [11]
0
0
Kentucky
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Country [12]
0
0
United States of America
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State/province [12]
0
0
Louisiana
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0
0
United States of America
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State/province [13]
0
0
Massachusetts
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Country [14]
0
0
United States of America
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State/province [14]
0
0
Minnesota
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Country [15]
0
0
United States of America
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State/province [15]
0
0
Missouri
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Country [16]
0
0
United States of America
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0
0
Montana
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Country [17]
0
0
United States of America
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0
0
New Jersey
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Country [18]
0
0
United States of America
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State/province [18]
0
0
New York
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Country [19]
0
0
United States of America
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State/province [19]
0
0
North Carolina
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0
0
United States of America
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0
0
Ohio
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Country [21]
0
0
United States of America
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0
0
Oregon
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0
0
United States of America
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0
0
Pennsylvania
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0
0
United States of America
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0
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Tennessee
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0
0
United States of America
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0
0
Texas
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0
0
United States of America
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0
0
Utah
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0
0
United States of America
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State/province [26]
0
0
Virginia
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Country [27]
0
0
United States of America
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State/province [27]
0
0
Wisconsin
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Country [28]
0
0
Brazil
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State/province [28]
0
0
São Paulo
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0
0
Brazil
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State/province [29]
0
0
Rio de Janeiro
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0
0
Canada
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State/province [30]
0
0
Manitoba
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0
0
Canada
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State/province [31]
0
0
Nova Scotia
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Country [32]
0
0
Canada
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State/province [32]
0
0
Ontario
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Country [33]
0
0
Canada
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State/province [33]
0
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Quebec
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Country [34]
0
0
France
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State/province [34]
0
0
Bron cedex
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0
0
France
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State/province [35]
0
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Grenoble cedex 9
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0
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France
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0
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Limoges cedex
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0
0
France
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0
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Nancy cedex
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0
0
France
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State/province [38]
0
0
Nice
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0
0
France
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0
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Nîmes cedex 9
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0
0
France
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0
0
Orléans cedex 2
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0
0
France
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0
0
Paris cedex 14
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0
0
France
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0
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Paris
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0
0
France
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State/province [43]
0
0
Tours cedex 9
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Country [44]
0
0
Hong Kong
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0
0
Shatin
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0
0
Japan
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0
0
Fukuoka
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0
0
Japan
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0
0
Hokkaido
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0
0
Japan
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0
0
Kanagawa
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0
0
Japan
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0
0
Osaka
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Country [49]
0
0
Japan
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State/province [49]
0
0
Yamanashi
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Country [50]
0
0
Norway
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State/province [50]
0
0
Bergen
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0
0
Norway
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0
0
Trondheim
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Country [52]
0
0
Russian Federation
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State/province [52]
0
0
Ekaterinburg
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Country [53]
0
0
Russian Federation
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0
0
Smolensk
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Country [54]
0
0
South Africa
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State/province [54]
0
0
Mpumalanga
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Country [55]
0
0
South Africa
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State/province [55]
0
0
Bellville
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Country [56]
0
0
South Africa
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State/province [56]
0
0
Observatory
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Country [57]
0
0
South Africa
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State/province [57]
0
0
Panorama
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Country [58]
0
0
South Africa
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State/province [58]
0
0
Rondebosch
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Country [59]
0
0
South Africa
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State/province [59]
0
0
Tygerberg
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Country [60]
0
0
South Africa
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State/province [60]
0
0
Worcester
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Country [61]
0
0
Spain
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State/province [61]
0
0
(Móstoles) Madrid
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Country [62]
0
0
Spain
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State/province [62]
0
0
Badalona
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Country [63]
0
0
Spain
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State/province [63]
0
0
Barcelona
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Country [64]
0
0
Spain
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State/province [64]
0
0
Getafe/Madrid
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Country [65]
0
0
Spain
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State/province [65]
0
0
L'Hospitalet de Llobregat
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Country [66]
0
0
Spain
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State/province [66]
0
0
Madrid
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Country [67]
0
0
Thailand
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State/province [67]
0
0
Bangkok
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Country [68]
0
0
United Kingdom
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State/province [68]
0
0
Lanarkshire
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Country [69]
0
0
United Kingdom
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State/province [69]
0
0
Merseyside
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Country [70]
0
0
United Kingdom
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State/province [70]
0
0
West Lothian
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Country [71]
0
0
United Kingdom
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State/province [71]
0
0
Bristol
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Country [72]
0
0
United Kingdom
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State/province [72]
0
0
Cardiff
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Country [73]
0
0
United Kingdom
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State/province [73]
0
0
Leeds
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Country [74]
0
0
United Kingdom
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State/province [74]
0
0
Leicester
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Country [75]
0
0
United Kingdom
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State/province [75]
0
0
London
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Country [76]
0
0
United Kingdom
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State/province [76]
0
0
Oxford
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Country [77]
0
0
United Kingdom
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State/province [77]
0
0
Southampton
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
GlaxoSmithKline
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Address
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Country
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Ethics approval
Ethics application status
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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.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT01014988
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
0
0
GSK Clinical Trials
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Address
0
0
GlaxoSmithKline
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Country
0
0
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Phone
0
0
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Fax
0
0
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Email
0
0
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Contact person for public queries
Name
0
0
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Address
0
0
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Country
0
0
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Phone
0
0
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Fax
0
0
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Email
0
0
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01014988
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