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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01014988




Registration number
NCT01014988
Ethics application status
Date submitted
16/11/2009
Date registered
17/11/2009
Date last updated
28/03/2017

Titles & IDs
Public title
Safety Study to Assess IV Zanamivir for Treatment of Influenza Infection in Patients Who Are in Hospital
Scientific title
An 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
Secondary ID [1] 0 0
113678
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Influenza, Human 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - zanamivir aqueous solution

Other: Single 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.


Treatment: Drugs: zanamivir aqueous solution
Zanamivir aqueous solution 10mg/mL is a clear, colorless, single use, sterile non-preserved preparation containing 10mg of zanamivir in each milliliter, and made isotonic with sodium chloride. It is presented in 20mL clear glass vials closed with rubber stoppers. Each vial contains 200mg of zanamivir.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Any Adverse Event (AE) Considered to be Related to Study Treatment
Timepoint [1] 0 0
Up to post-treatment (PT) + 23 days
Primary outcome [2] 0 0
Number of Participants With Any Severe or Grade 3/4 AEs
Timepoint [2] 0 0
Up to post-treatment (PT) + 23 days
Primary outcome [3] 0 0
Number of Participants With Any Severe or Grade 3/4 Treatment-related AE
Timepoint [3] 0 0
Up to post-treatment (PT) + 23 days
Primary outcome [4] 0 0
Number of Participants Who Permanently Discontinued the Study Treatment Due to an AE
Timepoint [4] 0 0
Up to 10 days
Primary outcome [5] 0 0
Number of Participants Who Were Permanently Discontinued From the Study Due to an AE
Timepoint [5] 0 0
Up to post-treatment (PT) + 23 days
Primary outcome [6] 0 0
Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5
Timepoint [6] 0 0
Baseline (Day 1) and Day 5
Primary outcome [7] 0 0
Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5
Timepoint [7] 0 0
Baseline (Day 1) and Day 5
Primary outcome [8] 0 0
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Toxicities
Timepoint [8] 0 0
Up to post-treatment (PT) + 23 days
Primary outcome [9] 0 0
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities
Timepoint [9] 0 0
Up to post-treatment (PT) + 23 days
Primary outcome [10] 0 0
Median Heart Rate at Baseline (Day 1) and Day 5
Timepoint [10] 0 0
Baseline (Day 1) and Day 5
Primary outcome [11] 0 0
Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5
Timepoint [11] 0 0
Baseline (Day 1) and Day 5
Primary outcome [12] 0 0
Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5
Timepoint [12] 0 0
Baseline (Day 1) and Day 5
Primary outcome [13] 0 0
Median Respiration Rate at Baseline (Day 1) and Day 5
Timepoint [13] 0 0
Baseline (Day 1) and Day 5
Primary outcome [14] 0 0
Median Body Temperature at Baseline (Day 1) and Day 5
Timepoint [14] 0 0
Baseline (Day 1) and Day 5
Primary outcome [15] 0 0
Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1)
Timepoint [15] 0 0
Baseline (Day 1)
Primary outcome [16] 0 0
Median Corrected QT Interval (QTc) for Heart Rate by Fridericia's Formula (QTcF) and Bazett's Formula (QTcB) at Baseline (Day 1) and Day 5
Timepoint [16] 0 0
Baseline (Day 1) and Day 5
Secondary outcome [1] 0 0
Median Time to Virologic Improvement
Timepoint [1] 0 0
Up to post-treatment (PT) + 23 days
Secondary outcome [2] 0 0
Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points
Timepoint [2] 0 0
Baseline (Day 1); Days 2, 3, 4, 5, 7, and 10; and post-treatment +2, +5, +9, +16, +23 days
Secondary outcome [3] 0 0
Mean Viral Susceptibility to Zanamivir at Baseline (Day 1) and All Post-Baseline Visits Collectively
Timepoint [3] 0 0
Baseline and up to post-treatment (PT) + 23 days
Secondary outcome [4] 0 0
Number of Participants With Treatment-emergent (TE) Mutations
Timepoint [4] 0 0
Baseline and up to post-treatment (PT) + 23 days
Secondary outcome [5] 0 0
Median Time to Resolution of Individual Vital Signs
Timepoint [5] 0 0
Up to post-treatment (PT) + 23 days
Secondary outcome [6] 0 0
Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation
Timepoint [6] 0 0
Up to post-treatment (PT) + 23 days
Secondary outcome [7] 0 0
Duration of Mechanical Ventilation and Supplemental Oxygen Use
Timepoint [7] 0 0
Up to discharge from the hospital
Secondary outcome [8] 0 0
Median Time to Return to Pre-morbid Functional Status
Timepoint [8] 0 0
Up to post-treatment (PT) + 23 days
Secondary outcome [9] 0 0
Number of Participants With the Indicated Mortality Status at Day 14 and Day 28
Timepoint [9] 0 0
Day 14 and Day 28
Secondary outcome [10] 0 0
Median Time to Clinical Response (Sustained Resolution) of All Vital Signs (Composite)
Timepoint [10] 0 0
Up to post-treatment (PT) + 23 days
Secondary outcome [11] 0 0
Number of Participants With Any AE Categorized as an Influenza Complication
Timepoint [11] 0 0
Up to post-treatment (PT) + 23 days
Secondary outcome [12] 0 0
Number of Participants Who Used Any Concomitant Antibiotic Medications for Complications of Influenza
Timepoint [12] 0 0
Up to post-treatment (PT) + 23 days
Secondary outcome [13] 0 0
Median Duration of Hospitalization and Intensive Care Unit (ICU) Stays
Timepoint [13] 0 0
Up to discharge from hospital
Secondary outcome [14] 0 0
Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion
Timepoint [14] 0 0
Day 1 and Days 3, 4, or 5
Secondary outcome [15] 0 0
Geometric Mean Area Under the Serum Drug Concentration-time Curve (AUC) Over a 12-hour Dosing Interval (AUC[0-tau]) and AUC Extrapolated to Infinity (AUC[0-inf]) of Zanamivir
Timepoint [15] 0 0
Day 1 and Days 3, 4, or 5
Secondary outcome [16] 0 0
Geometric Mean Terminal Half Life (t1/2) of Zanamivir
Timepoint [16] 0 0
Day 1 and Days 3, 4, or 5
Secondary outcome [17] 0 0
Geometric Mean Serum Clearance of Zanamivir
Timepoint [17] 0 0
Day 1 and Days 3, 4, or 5
Secondary outcome [18] 0 0
Geometric Mean Volume of Distribution (Vd) of Zanamivir
Timepoint [18] 0 0
Day 1 and Days 3, 4, or 5

Eligibility
Key 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. 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
* Subjects who are able to receive their first dose of study medication within seven days of experiencing influenza-like symptoms.
* 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 (or included as permitted by local regulatory authorities, IRBs/IECs or local laws).
* 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.
* UK subjects and subjects in Spain: Subjects should be in a high dependency or intensive care setting at the time of enrollment and either have severe and progressive illness on approved influenza antivirals, or are considered unsuitable for treatment with approved influenza antivirals.
* Subjects who have severe or progressive influenza illness on approved (fully licensed) influenza antivirals, or who are considered unsuitable or inappropriate for treatment with approved influenza antivirals, or who in the opinion of the investigator may benefit from IV zanamivir therapy.
Minimum age
6 Months
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.
* Child in care (CiC) as defined below:

A child who has been placed under the control or protection of an agency, organization, 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.
* Females who are pregnant (positive urine or serum pregnancy test at Baseline) or are breastfeeding.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2015
Sample size
Target
Accrual to date
Final
202
Recruitment in Australia
Recruitment state(s)
ACT,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Garran
Recruitment hospital [2] 0 0
GSK Investigational Site - Chermside
Recruitment hospital [3] 0 0
GSK Investigational Site - Herston
Recruitment hospital [4] 0 0
GSK Investigational Site - Adelaide
Recruitment hospital [5] 0 0
GSK Investigational Site - Bedford Park
Recruitment hospital [6] 0 0
GSK Investigational Site - Heidelberg
Recruitment hospital [7] 0 0
GSK Investigational Site - Perth
Recruitment hospital [8] 0 0
GSK Investigational Site - Subiaco
Recruitment postcode(s) [1] 0 0
2606 - Garran
Recruitment postcode(s) [2] 0 0
4032 - Chermside
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
5043 - Bedford Park
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment postcode(s) [7] 0 0
6000 - Perth
Recruitment postcode(s) [8] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
District of Columbia
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Georgia
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Kansas
Country [11] 0 0
United States of America
State/province [11] 0 0
Kentucky
Country [12] 0 0
United States of America
State/province [12] 0 0
Louisiana
Country [13] 0 0
United States of America
State/province [13] 0 0
Massachusetts
Country [14] 0 0
United States of America
State/province [14] 0 0
Minnesota
Country [15] 0 0
United States of America
State/province [15] 0 0
Missouri
Country [16] 0 0
United States of America
State/province [16] 0 0
Montana
Country [17] 0 0
United States of America
State/province [17] 0 0
New Jersey
Country [18] 0 0
United States of America
State/province [18] 0 0
New York
Country [19] 0 0
United States of America
State/province [19] 0 0
North Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
Ohio
Country [21] 0 0
United States of America
State/province [21] 0 0
Oregon
Country [22] 0 0
United States of America
State/province [22] 0 0
Pennsylvania
Country [23] 0 0
United States of America
State/province [23] 0 0
Tennessee
Country [24] 0 0
United States of America
State/province [24] 0 0
Texas
Country [25] 0 0
United States of America
State/province [25] 0 0
Utah
Country [26] 0 0
United States of America
State/province [26] 0 0
Virginia
Country [27] 0 0
United States of America
State/province [27] 0 0
Wisconsin
Country [28] 0 0
Brazil
State/province [28] 0 0
São Paulo
Country [29] 0 0
Brazil
State/province [29] 0 0
Rio de Janeiro
Country [30] 0 0
Canada
State/province [30] 0 0
Manitoba
Country [31] 0 0
Canada
State/province [31] 0 0
Nova Scotia
Country [32] 0 0
Canada
State/province [32] 0 0
Ontario
Country [33] 0 0
Canada
State/province [33] 0 0
Quebec
Country [34] 0 0
France
State/province [34] 0 0
Bron cedex
Country [35] 0 0
France
State/province [35] 0 0
Grenoble cedex 9
Country [36] 0 0
France
State/province [36] 0 0
Limoges cedex
Country [37] 0 0
France
State/province [37] 0 0
Nancy cedex
Country [38] 0 0
France
State/province [38] 0 0
Nice
Country [39] 0 0
France
State/province [39] 0 0
Nîmes cedex 9
Country [40] 0 0
France
State/province [40] 0 0
Orléans cedex 2
Country [41] 0 0
France
State/province [41] 0 0
Paris cedex 14
Country [42] 0 0
France
State/province [42] 0 0
Paris
Country [43] 0 0
France
State/province [43] 0 0
Tours cedex 9
Country [44] 0 0
Hong Kong
State/province [44] 0 0
Shatin
Country [45] 0 0
Japan
State/province [45] 0 0
Fukuoka
Country [46] 0 0
Japan
State/province [46] 0 0
Hokkaido
Country [47] 0 0
Japan
State/province [47] 0 0
Kanagawa
Country [48] 0 0
Japan
State/province [48] 0 0
Osaka
Country [49] 0 0
Japan
State/province [49] 0 0
Yamanashi
Country [50] 0 0
Norway
State/province [50] 0 0
Bergen
Country [51] 0 0
Norway
State/province [51] 0 0
Trondheim
Country [52] 0 0
Russian Federation
State/province [52] 0 0
Ekaterinburg
Country [53] 0 0
Russian Federation
State/province [53] 0 0
Smolensk
Country [54] 0 0
South Africa
State/province [54] 0 0
Mpumalanga
Country [55] 0 0
South Africa
State/province [55] 0 0
Bellville
Country [56] 0 0
South Africa
State/province [56] 0 0
Observatory
Country [57] 0 0
South Africa
State/province [57] 0 0
Panorama
Country [58] 0 0
South Africa
State/province [58] 0 0
Rondebosch
Country [59] 0 0
South Africa
State/province [59] 0 0
Tygerberg
Country [60] 0 0
South Africa
State/province [60] 0 0
Worcester
Country [61] 0 0
Spain
State/province [61] 0 0
(Móstoles) Madrid
Country [62] 0 0
Spain
State/province [62] 0 0
Badalona
Country [63] 0 0
Spain
State/province [63] 0 0
Barcelona
Country [64] 0 0
Spain
State/province [64] 0 0
Getafe/Madrid
Country [65] 0 0
Spain
State/province [65] 0 0
L'Hospitalet de Llobregat
Country [66] 0 0
Spain
State/province [66] 0 0
Madrid
Country [67] 0 0
Thailand
State/province [67] 0 0
Bangkok
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Lanarkshire
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Merseyside
Country [70] 0 0
United Kingdom
State/province [70] 0 0
West Lothian
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Bristol
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Cardiff
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Leeds
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Leicester
Country [75] 0 0
United Kingdom
State/province [75] 0 0
London
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Oxford
Country [77] 0 0
United Kingdom
State/province [77] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01014988
Trial related presentations / publications
Marty FM, Man CY, van der Horst C, Francois B, Garot D, Manez R, Thamlikitkul V, Lorente JA, Alvarez-Lerma F, Brealey D, Zhao HH, Weller S, Yates PJ, Peppercorn AF. Safety and pharmacokinetics of intravenous zanamivir treatment in hospitalized adults with influenza: an open-label, multicenter, single-arm, phase II study. J Infect Dis. 2014 Feb 15;209(4):542-50. doi: 10.1093/infdis/jit467. Epub 2013 Aug 27.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01014988