A Study of Intravenous Zanamivir Versus Oral Oseltamivir in Adults and Adolescents Hospitalized With Influenza.

• Register: ClinicalTrials.gov
• Last refreshed on: 13 May 2013
• Main ID: NCT01231620
• Date of registration: 28/10/2010
• Primary sponsor: GlaxoSmithKline
• Public title: A Study of Intravenous Zanamivir Versus Oral Oseltamivir in Adults and Adolescents Hospitalized With Influenza. ZORO
• Scientific title: A Phase III International, Randomized, Double-blind, Double-dummy Study to Evaluate the Efficacy and Safety of 300 mg or 600 mg of Intravenous Zanamivir Twice Daily Compared to 75 mg of Oral Oseltamivir Twice Daily in the Treatment of Hospitalized Adults and Adolescents With Influenza.
• Date of first enrolment: January 2011
• Target sample size: 462
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01231620
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Canada, China, Colombia, Czech Republic, Denmark, France, Germany, Greece, Hong Kong, Hungary, India, Korea, Republic of, Mexico, Netherlands, New Zealand, Norway, Pakistan, Poland, Russian Federation, Slovakia, South Africa, Spain, Taiwan, Thailand, United Kingdom, United States

Contacts

• Name: US GSK Clinical Call Center

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

- Male or female aged 16 years; 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.

- Vital signs criteria defined as 3 or more of the following at Baseline:

1. Presence of fever [oral temperature of 38°C or equivalent] at Baseline.
However, this requirement is waived if the subject has a history of fever within
in the 24 hours prior to Baseline; or, if the subject reported symptoms of
feverishness at some time during the 48 hours prior to Baseline.

AND at least 2 out of the following 4:

2. Oxygen saturation <95% on room air by trans-cutaneous method or need for any
supplemental oxygenation or ventilatory support, 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.

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

4. Heart rate >100 beats per minute.

5. Systolic blood pressure <90 mmHg.

- 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.

- Clinical symptoms of influenza with positive influenza diagnostic test result or
strong suspicion of influenza illness based on clinical symptoms and local
surveillance information.

- Subjects willing and able to give written informed consent to participate in the
study and to adhere to the procedures stated in the protocol, or legally acceptable
representative willing and able to give written informed consent on behalf of the
subject for minors, unconscious adults and those incapable of consenting themselves
due to their medical condition, or included as permitted by local regulatory
authorities, IRB/IECs or local laws.

- Severity of any medical illness that, in the Investigator's judgement, justifies
hospitalization of the subject for treatment and supportive care

- 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

Exclusion Criteria:

- Subjects who have taken more than a total of 3 days (6 doses) of approved
anti-influenza therapy (i.e. oral oseltamivir, oral inhaled zanamivir, oral
amantadine, oral rimantadine, or oral ribavirin) in the period from onset of symptoms
and prior to enrolment.

- 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 with creatinine clearance =10 mL/min who are not being treated with
continuous renal replacement therapy (CRRT).

- Subjects who require Extra Corporeal Membrane Oxygenation (ECMO) at Baseline

- 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.

- Liver toxicity criteria based on local laboratory results obtained within 24 hours of
Baseline:

1. ALT or AST 3xULN and bilirubin 2xULN

2. ALT 5xULN

- Underlying chronic liver disease with evidence of severe liver impairment.

- 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.

- Females who are pregnant or are breastfeeding.

- Treatment with investigational parenteral anti-influenza drugs (IV peramivir, IV
zanamivir or IV oseltamivir) in the 4 weeks prior to Baseline.

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



Age minimum: 16 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Influenza, Human

Intervention(s)

Drug: 300mg intravenous (IV) zanamivir and oral oseltamivir placebo

Drug: 600mg intravenous (IV) zanamivir and oral oseltamivir placebo

Drug: 75mg oral oseltamivir and intravenous zanamivir placebo

Primary Outcome(s)

Time to clinical response in subjects with confirmed influenza treated with 300 mg or 600 mg IV zanamivir compared with 75 mg oral oseltamivir [Time Frame: Up to 42 Days]

Secondary Outcome(s)

Changes in the Katz Index of Independence in Activities of Daily Living (ADL) score and time to return to pre-morbid level of activity [Time Frame: Baseline up to 42 days]

Changes in viral susceptibility [Time Frame: Baseline up to 42 days]

Disease progression and complications of influenza [Time Frame: Up to 42 days]

Duration of hospitalization and ICU (intense care unit) stay [Time Frame: Up to 42 days]

ECG(electrocardiogram) data [Time Frame: Up to day 4]

Mortality rate at Day 14 and Day 28 [Time Frame: Day 14 and day 28]

Pharmacokinetics of IV Zanamivir as measured by minimum or maximum serum concentration [Time Frame: Up to day 4]

Safety and tolerability as measured by the incidence of adverse events and laboratory abnormalities [Time Frame: Up to 42 days]

Summary of ventilation status [Time Frame: Up to 42 days]

Time to improvement of vital signs [Time Frame: Baseline up to 42 days]

Time to reduction in viral load and percentage of patients with undetectable viral RNA obtained from upper and lower respiratory samples [Time Frame: Baseline up to 42 days]

Secondary ID(s)

114373

Source(s) of Monetary Support

Please refer to primary and secondary sponsors