A Study of Intravenous Zanamivir in the Treatment of Hospitalized Patients With Influenza Infection - Full Text View

Purpose

This study will be an open-label, multi-center, single arm study to evaluate the safety and efficacy of IV zanamivir 600mg twice daily for 5 days in hospitalized subjects with laboratory confirmed influenza infection.

Condition	Intervention	Phase
Influenza, Human	Drug: Intravenous (IV) zanamivir	Phase 3

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Open-label, Multi-centre, Single Arm Study to Evaluate the Safety and Efficacy of Intravenous Zanamivir in the Treatment of Hospitalized Patients With Confirmed Influenza Infection (NAI115215)

Resource links provided by NLM:

MedlinePlus related topics: Flu

Drug Information available for: Zanamivir

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Incidence of AE [ Time Frame: Up to 33 days ] [ Designated as safety issue: Yes ]
Incidence of AE considered to be related to study treatment [ Time Frame: Up to 33 days ] [ Designated as safety issue: Yes ]
Incidence of grade 3/4 or severe AEs [ Time Frame: Up to 33 days ] [ Designated as safety issue: Yes ]
Incidence of grade 3/4 or severe AEs considered to be related to study treatment [ Time Frame: Up to 33 days ] [ Designated as safety issue: Yes ]
AEs leading to discontinuation of study drug or study [ Time Frame: Up to 33 days ] [ Designated as safety issue: Yes ]
SAEs [ Time Frame: Up to 33 days ] [ Designated as safety issue: Yes ]
Treatment related SAEs, fatal events [ Time Frame: Up to 33 days ] [ Designated as safety issue: Yes ]
Fatal events [ Time Frame: Up to 33 days ] [ Designated as safety issue: Yes ]
Clinical chemistry and hematology data values outside the normal range [ Time Frame: Baseline, day 3 and day 5 ] [ Designated as safety issue: Yes ]
Clinical laboratory data summarized based on changes from baseline [ Time Frame: Baseline, day 3 and day 5 ] [ Designated as safety issue: Yes ]
Toxicity shifts from baseline, treatment emergent toxicities [ Time Frame: Baseline, day 3 and day 5 ] [ Designated as safety issue: Yes ]
Heart rate will be listed and summarized by study visit [ Time Frame: Baseline up to 33 days ] [ Designated as safety issue: Yes ]
Blood pressure will be listed and summarized by study visit [ Time Frame: Baseline up to 33 days ] [ Designated as safety issue: Yes ]
Oxygen saturation will be listed and summarized by study visit [ Time Frame: Baseline up to 33 days ] [ Designated as safety issue: Yes ]
Respiration rate will be listed and summarized by study visit [ Time Frame: Baseline up to 33 days ] [ Designated as safety issue: Yes ]
Temperature will be listed and summarized by study visit [ Time Frame: baseline up to 33 days ] [ Designated as safety issue: Yes ]
Number of subjects who had abnormal and/or clinically significant ECG findings [ Time Frame: Up to day 4 ] [ Designated as safety issue: Yes ]
Percentage of subjects who had abnormal and/or clinically significant ECG findings [ Time Frame: Up to day 4 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

The time to clinical response [ Time Frame: Up to 33 days ] [ Designated as safety issue: No ]
Time to return to pre-morbid level of activity [ Time Frame: Baseline up to 33 days ] [ Designated as safety issue: No ]
Summary of ventilation status [ Time Frame: Up to 33 days ] [ Designated as safety issue: No ]
Length of ICU and hospital stays [ Time Frame: Up to 33 days ] [ Designated as safety issue: No ]
Viral susceptibility to zanamivir at Baseline and throughout treatment [ Time Frame: Baseline up to 33 days ] [ Designated as safety issue: No ]
Frequency of resistance emergence to zanamivir [ Time Frame: Baseline up to 33 days ] [ Designated as safety issue: No ]
Time to absence of fever [ Time Frame: Baseline up to 33 days ] [ Designated as safety issue: No ]
Time to improved respiratory status [ Time Frame: Baseline up to 33 days ] [ Designated as safety issue: No ]
Time to improved oxgen saturation [ Time Frame: Baseline up to 33 days ] [ Designated as safety issue: No ]
Time to improved heart rate [ Time Frame: Baseline up to 33 days ] [ Designated as safety issue: No ]
Time to improved systolic blood pressure [ Time Frame: Baseline up to 33 days ] [ Designated as safety issue: No ]
Incidence of clinical symptoms of influenza [ Time Frame: Up to 33 days ] [ Designated as safety issue: No ]
Duration of clinical symptoms of influenza [ Time Frame: Up to 33 days ] [ Designated as safety issue: No ]
Incidence of complications of influenza [ Time Frame: Up to 33 days ] [ Designated as safety issue: No ]
Influenza associated antibiotic use [ Time Frame: Up to 33 days ] [ Designated as safety issue: No ]
Time to reduction in viral load [ Time Frame: Baseline up to 33 days ] [ Designated as safety issue: No ]
Percentage of patients with undetectable viral RNA obtained from nasopharyngeal samples [ Time Frame: Baseline up to 33 days ] [ Designated as safety issue: No ]
Percentage of patients with undetectable viral RNA obtained from lower respiratory samples [ Time Frame: Baseline up to 33 days ] [ Designated as safety issue: No ]

Enrollment:	21
Study Start Date:	January 2012
Study Completion Date:	April 2013
Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Intravenous (IV) zanamivir 600mg twice daily 600mg of IV zanamivir infusion twice daily	Drug: Intravenous (IV) zanamivir Zanamivir aqueous solution 10mg/mL, 600mg of IV zanamivir infusion twice daily for 5 days

Detailed Description:

Adult subjects and adolescent subjects (≥50 kg) with normal renal function will receive 600mg per dose. Subjects with renal impairment will receive an adjusted dose based on calculated creatinine clearance. 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.

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. For subjects who have been discharged from hospital, the Post-Treatment +2, +5, +9 and +16 Days Assessments can be made by telephone contact.

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female aged greater than or equal to 16 years 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. of child-bearing potential, has a negative pregnancy test at Baseline, and agrees to use protocol specified methods of birth control while on study.
Subjects who have laboratory 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.
Presence of fever [oral temperature of >=38 deg C, rectal, tympanic of >=38.5 deg C or axilla >=37.4 deg C] at Baseline. However, this requirement is waived if the subject has a history of fever within the 48 hours prior to Baseline and has been administered any antipyretic(s) in the 48 hours prior to Baseline.
Hospitalized subjects with symptomatic influenza as defined by ANY of the following.
1. Moderate to severe tachypnea (respiratory rate >=24/minute) OR
2. Moderate to severe dyspnea (unable to speak in full sentences) OR
3. Arterial 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 arterial oxygen saturation of at least 3% below the patient's historical baseline oxygen saturation will satisfy this criterion OR
4. Hemodynamic instability, defined as systolic blood pressure <90 mmHg or heart rate >100 beats per minute OR
5. Subject who became dehydrated and need whole-body management by hospitalization.
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.
Subjects/legally acceptable representative of unconscious adults willing and able to give written informed consent to participate in the study, and subjects willing to adhere to the procedures stated in the protocol.

Exclusion Criteria:

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 who require Extra Corporeal Membrane Oxygenation (ECMO) at Baseline (enrolled subject who subsequently require ECMO may continue in the study).
Liver toxicity criteria based on local laboratory results obtained at Baseline:
1. ALT or AST >=3xULN and bilirubin >=2xULN
2. ALT >=5xULN
Underlying chronic liver disease with evidence of severe liver impairment (Child-Pugh Class C).
History of severe cardiac disease or clinically significant arrhythmia (either on ECG or by history) which, in the opinion of the investigator or sub-investigator, will interfere with the safety of the individual subject.
Females who are pregnant (positive urine or serum pregnancy test at Baseline) or are breastfeeding.
QT criteria at Baseline as defined below:
1. QTcB or QTcF >480 msec
2. If a subject has bundle branch block then criteria is QTcB or QTcF >510 msec
Subject has participated in any study using an investigational drug during the previous 30 days.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01527110

Locations

Japan
GSK Investigational Site
Fukuoka, Japan, 816-0864
GSK Investigational Site
Kanagawa, Japan, 247-8533
GSK Investigational Site
Osaka, Japan, 581-0011

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01527110 History of Changes
Other Study ID Numbers:	115215
Study First Received:	December 8, 2011
Last Updated:	May 16, 2013
Health Authority:	Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by GlaxoSmithKline:

zanamivir
Seasonal Influenza
H1N1
intravenous
neuraminidase inhibitor

Pandemic
Relenza
Influenza B virus
Influenza A virus

Additional relevant MeSH terms:

Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Zanamivir

Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 19, 2013