AI114373: A Phase III international, randomized, doubleblind, 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. - N/A

• Conditions: hospitalised adults and adolescents with influenza; MedDRA version: 12.1Level: LLTClassification code 10022000Term: Influenza

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-11-16
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 462

Inclusion Criteria

Subjects eligible for enrolment in the study must meet all of the following criteria:
1.Male or female aged greater than or equal16 years; 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 defined as 3 or more of the following at Baseline:
•Presence of fever [oral temperature of =38°C (=100.4°F), rectal, 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 and has been administered any antipyretic(s) in the 24 hours prior to Baseline; 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:
•Arterial oxygen saturation <95% on room air by trans-cutaneous method, 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.
•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 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
Clinical symptoms of influenza with negative RAT or other influenza test result.
•Subjects with a negative RAT or other clinical laboratory test may be enrolled based on strong clinical suspicion of influenza illness (for example, investigator is aware of reports of influenza in the local community).
5.Subjects/legal guardians of minors and unconscious adults willi

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 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.
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 (Child-Pugh Class C).
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.QT criteria at Baseline as defined below:
•QTcB or QTcF >500 msec
•If a subject has bundle branch block then criteria is QTcB or QTcF >530 msec
14.French subjects: the French subject has participated in any study using an investigational drug during the previous 30 days.

Study & Design

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