A Study of Intravenous Zanamivir Versus Oral Oseltamivir in Adults andAdolescents Hospitalized With Influenza

Phase 1

• Conditions: hospitalised adults and adolescents with influenza; MedDRA version: 17.1Level: PTClassification code 10022000Term: InfluenzaSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2010-021621-12-PL
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-02-08
• Last Update Posted: 16 August 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

Subjects eligible for enrolment in the study must meet all of the following criteria:
1.Male or female aged = 16 years; (= 18 years where required by local
regulatory authorities or IRB/IECs); a female is eligible to enter and
participate in the study if she is:
a.of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or,
b.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 +28 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).
2. Vital signs criteria at Baseline defined as:
- Presence of fever [oral temperature of =38°C (=100.4°F), rectal/core,
tympanic of =38.5°C (=101.3°F), or axilla =37.4°C (=99.3°F)] at
Baseline. However, this requirement is waived if:

i. The subject has a history of fever within the 24 hours prior to Baseline,
with or without administration of antipyretic(s) or,

ii. The subject has no history of documented fever as defined above, but
reports a symptom of feverishness at some time during the 48 hours
prior to Baseline.

AND at least 2 out of the following 4:

- 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 oxygen saturation of at least 3%
below the patient's historical baseline oxygen saturation will satisfy this
criterion.

- Respiration rate >24 breaths per minute. For those subjects who
require ventilatory support or oxygen supplementation, this requirement
is waived.

- Heart rate >100 beats per minute.

- Systolic blood pressure <90 mmHg.
3.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.
4. Clinical symptoms of influenza with positive influenza diagnostic test
result.

- Subjects who have 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.
OR
Strong suspicion of influenza illness based on clinical symptoms and
local
surveillance information.

- Subjects with a negative RAT or pending other influenza laboratory test
may be enrolled.

5. Subjects willing and able to give written informed consent to
participate in the study and to adhere

Exclusion Criteria

Subjects meeting any of the following criteria must not be enrolled in the
study:
1. Subjects who have taken more than a total of 3 days (6 doses) of
approved antiinfluenza therapy (i.e. oral oseltamivir, oral inhaled
zanamivir, oral amantadine, oral rimantadine, oral ribavirin, or IV
peramivir, where approved) in the period from onset of symptoms and
prior to enrolment.
2.Subjects who, in the opinion of the investigator, are not likely to
survive beyond 48 hours from Baseline.
3.Subjects who are considered to require concurrent therapy with
another influenza antiviral medication.
4.Subjects who are known or suspected to be hypersensitive to any
component of the study medications.
5.Subjects with creatinine clearance =10 mL/min who are not being
treated with continuous renal replacement therapy (CRRT).
6.Subjects who require Extra Corporeal Membrane Oxygenation (ECMO)
at Baseline (enrolled subject who subsequently require ECMO may
continue in the study).
7.Subjects who require routine/intermittent hemodialysis or continuous
peritoneal dialysis (due to inability to provide appropriate dosing
schedule for oseltamivir) at Baseline. CRRT modalities are allowed
(CVVH, CVVHD, CVVHDF, SLED, SCUF, CAVH, CAVHD, CAVHDF).
8.Liver toxicity criteria based on local laboratory results obtained within
24 hours of Baseline:
•ALT or AST =3xULN and bilirubin =2xULN
•ALT =5xULN
9. Underlying chronic liver disease with evidence of severe liver
impairment.
10.History of severe 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.
11.Females who are pregnant (positive urine or serum pregnancy test at
Baseline) or are breastfeeding.
12.Treatment with investigational parenteral anti-influenza drugs (IV
peramivir, IV zanamivir or IV oseltamivir) in the 4 weeks prior to
Baseline.
13. Exclusion criterion #13 removed in Protocol Amendment 02.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified