Safety Study to Assess IV Zanamivir for Treatment of Influenza Infection in Patients Who Are in Hospital

This study will be an open-label, Phase II, multi-center, single arm study to evaluate the
safety and tolerability of IV zanamivir 600mg twice daily for 5 days in hospitalized
subjects with laboratory confirmed influenza infection. The initial 5-day treatment course
may be extended for up to 5 additional days if viral shedding is determined to be ongoing or
if clinical symptoms warrant further treatment with IV zanamivir.

Approximately 200 subjects will be enrolled into the study (approximately 150
adult/adolescent subjects and approximately 50 pediatric subjects). Adult (>/= 18 years of
age) with normal renal function will receive 600mg per dose. Pediatric (6 months to <13
years)/adolescent (>13 years to <18 years) subjects will receive an age-adjusted,
weight-based dose (not to exceed the 600 mg adult dose) intended to provide comparable
systemic exposures to 600mg in adults. Subjects with renal impairment will receive an
adjusted dose based on calculated creatinine clearance and renal replacement modality.

Serum pharmacokinetic assessments will be performed in subjects across all age groups
wherever possible. Pharmacokinetic analyses will be conducted, in real-time to the extent
possible, when 4 subjects (from whom samples can be obtained) are enrolled in each of the
following age cohorts: 6 months to less than 1 year; 1 to less than 2 years, and 2 to less
than 6 years to determine the need for pediatric dose adjustments. PK assessments are
required in the first 4 subjects enrolled in the 6 months to less than 1 year age cohort,
and PK data must be analyzed and IV zanamivir dosage must be reviewed before additional
subjects in this age cohort can be enrolled.

The study duration is approximately 28 days for subjects whose treatment duration is 5 days,
and up to approximately 33 days for subjects whose treatment duration is extended to a
maximum of 10 days. The study will consist of Pre-dose Baseline Assessments (Day 1), During
Treatment Assessments (Days 1 to 5, and up to Day 10), and Follow-up Assessments on the
following days: Post-Treatment +2 +5, +9, +16 and +23 Days. If the first dose of IV
zanamivir is administered in the afternoon/evening of Day 1, the twice daily dosing schedule
will result in one treatment day encompassing two calendar days. For subjects who have been
discharged from hospital, the Post-Treatment +2, +5, +9 and +16 Days Assessments can be made
by telephone contact.

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.

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.