A Study of Intravenous Zanamivir in the Treatment of Hospitalized Patients With Influenza Infection
Condition: Influenza, Human
MeSH terms: Influenza, Human
Intervention: Intravenous (IV) zanamivir
Intervention description: Zanamivir aqueous solution 10mg/mL, 600mg of IV zanamivir infusion twice daily for 5 days
Intervention MeSH terms: Zanamivir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: zanamivir; Seasonal Influenza; H1N1; intravenous; neuraminidase inhibitor; Pandemic; Relenza; Influenza B virus; Influenza A virus

Summary:

      This study will be an open-label, multi-center, single arm study to evaluate the safety and
      efficacy of IV zanamivir 600mg twice daily for 5 days in hospitalized subjects with
      laboratory confirmed influenza infection.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female aged greater than or equal to 16 years 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 use protocol specified methods of birth control while on study.

          -  Subjects who have laboratory confirmed influenza as determined by a positive result in
             a rapid antigen test (RAT) for influenza A or influenza B, or a laboratory test for
             influenza including but not limited to influenza virus antigen test, virus culture or
             RT-PCR test.

          -  Presence of fever [oral temperature of >=38 deg C, rectal, tympanic of >=38.5 deg C or
             axilla >=37.4 deg C] at Baseline. However, this requirement is waived if the subject
             has a history of fever within the 48 hours prior to Baseline and has been administered
             any antipyretic(s) in the 48 hours prior to Baseline.

          -  Hospitalized subjects with symptomatic influenza as defined by ANY of the following.

               1. Moderate to severe tachypnea (respiratory rate >=24/minute) OR

               2. Moderate to severe dyspnea (unable to speak in full sentences) OR

               3. Arterial oxygen saturation <95% on room air by trans-cutaneous method, or need
                  for any supplemental oxygenation or ventilatory support [mechanical ventilation,
                  bi-level positive airway pressure (bipap), continuous positive airway pressure
                  (cpap)], or increase in oxygen supplementation requirement of >=2 litres for
                  subjects with chronic oxygen dependency. For those subjects with a history of
                  chronic hypoxia (without supplemental oxygen), an arterial oxygen saturation of
                  at least 3% below the patient's historical baseline oxygen saturation will
                  satisfy this criterion OR

               4. Hemodynamic instability, defined as systolic blood pressure <90 mmHg or heart
                  rate >100 beats per minute OR

               5. Subject who became dehydrated and need whole-body management by hospitalization.

          -  Onset of influenza symptoms within 6 days prior to study enrolment. Symptoms may
             include cough, dyspnea, sore throat, feverishness, myalgias, headache, nasal symptoms
             (rhinorrhea, congestion), fatigue, diarrhea, anorexia, nausea and vomiting.

          -  Subjects/legally acceptable representative of unconscious adults willing and able to
             give written informed consent to participate in the study, and subjects willing to
             adhere to the procedures stated in the protocol.

        Exclusion Criteria:

          -  Subjects who, in the opinion of the investigator, are not likely to survive beyond 48
             hours from Baseline.

          -  Subjects who are considered to require concurrent therapy with another influenza
             antiviral medication.

          -  Subjects who are known or suspected to be hypersensitive to any component of the study
             medications.

          -  Subjects who require Extra Corporeal Membrane Oxygenation (ECMO) at Baseline (enrolled
             subject who subsequently require ECMO may continue in the study).

          -  Liver toxicity criteria based on local laboratory results obtained at Baseline:

               1. ALT or AST >=3xULN and bilirubin >=2xULN

               2. ALT >=5xULN

          -  Underlying chronic liver disease with evidence of severe liver impairment (Child-Pugh
             Class C).

          -  History of severe cardiac disease or clinically significant arrhythmia (either on ECG
             or by history) which, in the opinion of the investigator or sub-investigator, will
             interfere with the safety of the individual subject.

          -  Females who are pregnant (positive urine or serum pregnancy test at Baseline) or are
             breastfeeding.

          -  QT criteria at Baseline as defined below:

               1. QTcB or QTcF >480 msec

               2. If a subject has bundle branch block then criteria is QTcB or QTcF >510 msec

          -  Subject has participated in any study using an investigational drug during the
             previous 30 days.