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Safety study to assess IV zanamivir for treatment of influenza infection in patients who are in hospital

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GSK study ID

113678

See study documents

Clinicaltrials.gov ID

NCT01014988

See results summary

EudraCT ID

2009-016035-35

EU CT Number

Not applicable

Trial status

Study complete

Overview

Eligibility

Locations

Study documents

Results summary

Plain language summaries

Additional information

Trial overview

Official 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

Trial description: 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.

Primary purpose:

Treatment

Trial design:

Single Group Assignment

Masking:

None (Open Label)

Allocation:

Not applicable

Primary outcomes:

Number of participants with any adverse event (AE) considered to be related to study treatment

Timeframe: Up to post-treatment (PT) + 23 days

Number of participants with any severe or Grade 3/4 AEs

Timeframe: Up to post-treatment (PT) + 23 days

Number of participants with any severe or Grade 3/4 treatment-related AE

Timeframe: Up to post-treatment (PT) + 23 days

Number of participants who permanently discontinued the study treatment due to an AE

Timeframe: Up to 10 days

Number of participants who were permanently discontinued from the study due to an AE

Timeframe: Up to post-treatment (PT) + 23 days

Number of participants with the indicated clinical chemistry values relative to the normal range at Baseline (Day 1) and Day 5

Timeframe: Baseline (Day 1) and Day 5

Number of participants with the indicated hematology values relative to the normal range at Baseline (Day 1) and Day 5

Timeframe: Baseline (Day 1) and Day 5

Number of participants with the indicated treatment-emergent (TE) Grade 3/4 clinical chemistry toxicities

Timeframe: Up to post-treatment (PT) + 23 days

Number of participants with the indicated treatment-emergent (TE) Grade 3/4 hematology toxicities

Timeframe: Up to post-treatment (PT) + 23 days

Median heart rate at Baseline (Day 1) and Day 5

Timeframe: Baseline (Day 1) and Day 5

Median systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Baseline (Day 1) and Day 5

Timeframe: Baseline (Day 1) and Day 5

Median oxygen saturation measured via transcutaneous oximetry (TCPO2) at Baseline (Day 1) and Day 5

Timeframe: Baseline (Day 1) and Day 5

Median respiration rate at Baseline (Day 1) and Day 5

Timeframe: Baseline (Day 1) and Day 5

Median body temperature at Baseline (Day 1) and Day 5

Timeframe: Baseline (Day 1) and Day 5

Number of participants assessed as normal/abnormal (clinically significant [CS] and not clinically significant [NCS]) for 12-lead electrocardiogram (ECG) at Baseline (Day 1)

Timeframe: Baseline (Day 1)

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

Timeframe: Baseline (Day 1) and Day 5

Secondary outcomes:

Median time to virologic improvement

Timeframe: Up to post-treatment (PT) + 23 days

Median change from Baseline (Influenza A or B quantitative PCR, as appropriate) in viral load at the indicated time points

Timeframe: Baseline (Day 1); Days 2, 3, 4, 5, 7, and 10; and post-treatment +2, +5, +9, +16, +23 days

Mean viral susceptibility to zanamivir at Baseline (Day 1) and all Post-Baseline visits collectively

Timeframe: Baseline and up to post-treatment (PT) + 23 days

Number of participants with treatment-emergent (TE) mutations

Timeframe: Baseline and up to post-treatment (PT) + 23 days

Median time to resolution of individual vital signs

Timeframe: Up to post-treatment (PT) + 23 days

Number of participants with the indicated ventilation status: modality of supplemental oxygen delivery and mechanical ventilation

Timeframe: Up to post-treatment (PT) + 23 days

Duration of mechanical ventilation and supplemental oxygen use

Timeframe: Up to discharge from the hospital

Median time to return to pre-morbid functional status

Timeframe: Up to post-treatment (PT) + 23 days

Number of participants with the indicated mortality status at Day 14 and Day 28

Timeframe: Day 14 and Day 28

Median time to clinical response (sustained resolution) of all vital signs (composite)

Timeframe: Up to post-treatment (PT) + 23 days

Number of participants with any AE categorized as an influenza complication

Timeframe: Up to post-treatment (PT) + 23 days

Number of participants who used any concomitant antibiotic medications for complications of influenza

Timeframe: Up to post-treatment (PT) + 23 days

Median duration of hospitalization and intensive care unit (ICU) stays

Timeframe: Up to discharge from hospital

Geometric mean maximum serum concentration (Cmax) of zanamivir at the end of infusion

Timeframe: Day 1 and Days 3, 4, or 5

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

Timeframe: Day 1 and Days 3, 4, or 5

Geometric mean terminal half life (t1/2) of zanamivir

Timeframe: Day 1 and Days 3, 4, or 5

Geometric mean serum clearance of zanamivir

Timeframe: Day 1 and Days 3, 4, or 5

Geometric mean volume of distribution (Vd) of zanamivir

Timeframe: Day 1 and Days 3, 4, or 5

Interventions:

Drug: zanamivir aqueous solution

Enrollment:

202

Primary completion date:

2015-13-02

Observational study model:

Not applicable

Time perspective:

Not applicable

Clinical publications:

F Marty, CY Man, C van der Horst, B Francois, D Garot, RM Mendiluce, V Thamlikitkul, JA Lorente, FA Lerma, D Brearley, HH Zhao, S Weller, PJ Yates, A Peppercorn.Safety, tolerability and pharmacokinetics of intravenous zanamivir treatment in hospitalized adults with influenza: An open-label, multicenter, single-arm, phase II study.J Infect Dis.2014;209:542-50

Peiying Zuo, Jon Collins, Malek Okour, Aline Barth, Denise Shortino, Phillip Yates, Grace Roberts, Helen A Watson, Amanda Peppercorn, Mohammad Hossain .Population Pharmacokinetic/Pharmacodynamic Analysis of Intravenous Zanamivir in Healthy Adults and Hospitalized Adult and Pediatric Subjects with Influenza.Clin Transl Sci.2019; DOI: 10.1111/cts.12697 PMID: 31664778

Medical condition

Influenza, Human

Product

zanamivir

Collaborators

Not applicable

Study date(s)

November 2009 to February 2015

Type

Interventional

Phase

Participation criteria

Sex

Female & Male

Age

6+ years

Accepts healthy volunteers

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:
a. of non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or,

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.

Inclusion and exclusion criteria

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: 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 +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.

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.

Trial location(s)

Location

Status

Location

GSK Investigational Site

(Móstoles) Madrid, Spain, 28935

Status

Study Complete

Location

GSK Investigational Site

Adelaide, South Australia, Australia, 5000

Status

Study Complete

Location

GSK Investigational Site

Atlanta, Georgia, United States, 30322

Status

Study Complete

Location

GSK Investigational Site

Badalona, Spain, 08916

Status

Study Complete

Location

GSK Investigational Site

Bangkok, Thailand, 10700

Status

Study Complete

Location

GSK Investigational Site

Barcelona, Spain, 08003

Status

Study Complete

Showing 1 - 6 of 51 Results

Study documents

Clinical study report

Available language(s): English

Download document(s)

Scientific result summary

Available language(s): English

Download document(s)

If you wish to request for full study report, please contact - [email protected]

Results overview

Results posted on ClinicalTrials.gov

Recruitment status

Study complete

Actual primary completion date

2015-13-02

Actual study completion date

2015-13-02

Plain language summaries

Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.