A Study of Intravenous Zanamivir Versus Oral Oseltamivir in Adults and Adolescents Hospitalized With Influenza
Condition: Influenza, Human
MeSH terms: Influenza, Human
Intervention: Zanamivir; Placebo to match zanamivir; Oseltamivir; Placebo to match oseltamivir
Intervention description: Zanamivir aqueous solution, 10 mg/mL, will be provided as a single use, sterile clear, colorless preparation in 20 mL clear glass vials.; Placebo to match IV zanamivir will be provided as a normal saline solution of a matched volume.; Oseltamivir will be provided as over-encapsulated 75 mg capsules.; Placebo to match oral oseltamivir will be provided as capsules with a common excipient of appropriate quality.
Intervention MeSH terms: Oseltamivir; Zanamivir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 626.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: Seasonal Influenza; Pandemic; Orthomyxoviridae Infections; Influenza; Influenza A Virus, H1N1 Subtype; Enzyme Inhibitors; Influenza, seasonal; Respiratory Tract Diseases; Zanamivir; Pharmacologic Actions; Antiviral Agents; Anti-Infective Agents; H1N1; Neuraminidase inhibitor; Influenza B virus

Summary:

      The purpose of this study is to test the safety and efficacy of zanamivir given intravenously
      and how well it works at two different doses in hospitalized adolescents and adults with flu.
      Zanamivir will be compared with oseltamivir, which is used for treating flu.
    

Eligibility 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 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.