Safety Study to Assess IV Zanamivir for Treatment of Influenza Infection in Patients Who Are in Hospital (NAI113678)

Tracking Information

Start Date  ICMJENovember 2009
Estimated Primary Completion DateOctober 2010   (final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE 
 (submitted: November 16, 2009)
  • Heart rate, blood pressure, oxygen saturation, respiration rate and temperature will be summarized by visit, change from baseline of the vital signs will be summarized. [ Time Frame: During the course of the study ] [ Designated as safety issue: Yes ]
  • Number and percentage of subjects who had abnormal and/or clinically significant ECG findings, ECG interval data and change from baseline, QTc interval will be calculated [ Time Frame: During the course of the study ] [ Designated as safety issue: Yes ]
  • Incidence of AEs, including AE considered to be related to study treatment, grade 3/4 or severe AEs and those treatment related, AEs leading to discontinuation of study drug or study, SAEs, treatment related SAEs, fatal events [ Time Frame: Duration of the study ] [ Designated as safety issue: Yes ]
  • Clinical chemistry and hematology data values outside the normal range, Clinical laboratory data summarized based on changes from baseline and toxicity shifts from baseline, treatment emergent toxicities [ Time Frame: Duration of the study ] [ Designated as safety issue: Yes ]
Original Primary Outcome Measures  ICMJESame as current
Change HistoryComplete list of historical versions of study NCT01014988 on Archive Site
Current Secondary Outcome Measures  ICMJE 
 (submitted: November 16, 2009)
  • Viral susceptibility to zanamivir at baseline, and if virus present, at subsequent timepoints during the study, as assessed by NA sequence analysis and NA enzyme inhibition assay [ Time Frame: Baseline and all subsequent timepoints during the study ] [ Designated as safety issue: No ]
  • Time to no detectable viral RNA and to absence of cultivable virus in nasopharyngeal samples. [ Time Frame: During the course of the study ] [ Designated as safety issue: No ]
  • Proportion of subjects who are negative by virus culture (and RT-PCR if available) in nasopharyngeal samples [ Time Frame: Day 3 and all subsequent timepoints during the study ] [ Designated as safety issue: No ]
  • Frequency of resistance emergence to zanamivir [ Time Frame: During the course of the study ] [ Designated as safety issue: No ]
  • All cause mortality rate [ Time Frame: Durning the course of the study ] [ Designated as safety issue: Yes ]
  • Incidence of complications of influenza and associated antibiotic use [ Time Frame: During the course of the study ] [ Designated as safety issue: Yes ]
  • Ventilation status: duration of supplemental oxygen and of mechanical ventilation [ Time Frame: During the course of the study ] [ Designated as safety issue: Yes ]
  • Time to afebrile status [ Time Frame: During the course of the study ] [ Designated as safety issue: Yes ]
  • Length of ICU and hospital stays [ Time Frame: During the course of the study ] [ Designated as safety issue: No ]
  • Level of activity (bed rest, limited ambulation or unrestricted) over time and time to return to pre-morbid functional status [ Time Frame: During the course of the study ] [ Designated as safety issue: No ]
  • Change in quantitative viral load over time and change from baseline measured from nasopharyngeal swab samples, as determined by quantitative virus culture (and retrospectively by RT-PCR, if available) [ Time Frame: During the course of the study ] [ Designated as safety issue: No ]

Descriptive Information

Brief Title  ICMJESafety Study to Assess IV Zanamivir for Treatment of Influenza Infection in Patients Who Are in Hospital
Official Title  ICMJEAn Open-Label, Multi-Center, Single Arm Study to Evaluate the Safety and Tolerability of Intravenous Zanamivir in the Treatment of Hospitalized Adult, Adolescent and Pediatric Subjects With Confirmed Influenza Infection
Brief Summary

The purpose of this study is to determine whether zanamivir aqueous solution given by intravenous injection is safe in treating hospitalized patients with confirmed influenza infection. A single arm open-label design has been selected to achieve the primary objective of providing regulatory authorities with safety data on IV zanamivir.

Detailed Description

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 and adolescent subjects with normal renal function will receive 600mg per dose. Pediatric subjects (weight less than or equal to 37kg) will receive a weight-adjusted 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.

Serum pharmacokinetic assessments will be performed in subjects 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.

Study PhasePhase II
Study Type  ICMJEInterventional
Study Design  ICMJETreatment, Open Label, Single Group Assignment, Safety Study
Condition  ICMJE
  • Influenza A Virus, H1N1 Subtype
  • Influenza B Virus
  • Influenza, Human
  • Influenza, Seasonal
Intervention  ICMJEDrug: zanamivir aqueous solution
Zanamivir aqueous solution 10mg/mL is a clear, colorless, single use, sterile nonpreserved preparation containing 10mg of zanamivir in each millilitre, and made isotonic with sodium chloride. It is presented in 20mL clear glass vials closed with rubber stoppers. Each vial contains 200mg of zanamivir.
Study Arms / Comparison GroupsSingle Arm
A single arm open-label design has been selected to achieve the primary objective of providing regulatory authorities with safety data on IV zanamivir in an expedited manner. This study design also facilitates the provision of safety data on a real-time basis, if necessary.
Intervention: Drug: zanamivir aqueous solution

Recruitment Information

Estimated Enrollment  ICMJE150
Estimated Completion DateOctober 2010
Estimated Primary Completion DateOctober 2010   (final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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. known to be pregnant at Baseline; or,
    3. 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 as defined by ANY of the following:
  • Evidence of lower respiratory tract infection by one of the following:
  • New infiltrate on chest radiograph
  • Oxygen saturation <95% by transcutaneous (fingertip) oximetry on room air (or as adjusted for altitude) with no known underlying lung disease, or oxygen saturation >5% less than patient's baseline if known underlying lung disease
  • 15 mmHg or greater decrease in alveoloar-arterial oxygen gradient compared to the patient's known or expected baseline gradient
  • Symptoms associated with respiratory distress (e.g. dyspnea)
  • Signs and symptoms consistent with influenza requiring hospitalization.
  • Presence of fever at time of screening of ≥ 38.0 °C (≥ 100.0 °F) taken orally, or ≥ 38.5 °C (≥ 101.2 °F) taken rectally. However, this requirement is waived (1) if the subject has a history of fever within the 24 hours prior to screening and has been administered any antipyretic(s) in the 24 hours prior to screening, or (2) if 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 screening.
  • Subjects who are able to receive their first dose of study medication within seven days of experiencing influenza-like symptoms.
  • Subjects anticipated to require hospitalization for 5 or more days.
  • 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.
  • 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, 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.
  • QT criteria at baseline as defined below:
  • QTcB or QTcF > 500 msec
  • If subject has bundle branch block then criteria is QTcB or QTcF > 530 msec
  • Child in care (CiC) as defined below:

A child who has been placed under the control or protection of an agency, organisation, 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.

Ages6 Months and older
Accepts Healthy VolunteersNo
Contacts  ICMJE
Contact: US GSK Clinical Trials Call Center877-379-3718
Location Countries  ICMJEUnited States,   Canada,   France,   Russian Federation,   Spain,   United Kingdom

Administrative Information

Responsible PartyStudy Director, GSK
Study ID Numbers  ICMJE113678
Study Sponsor  ICMJEGlaxoSmithKline
Collaborators  ICMJE 
Investigators  ICMJE
Study Director:GSK Clinical TrialsGlaxoSmithKline
Information Provided ByGlaxoSmithKline