AzTrials
AzTrials

Influenza, HumanPhase 2NCT01014988

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

A Phase 2 study testing zanamivir aqueous solution in people with Influenza, Human, run by GlaxoSmithKline at 110 sites in 13 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 6 months and older
Conditions the study is for
Influenza, Human
What is being tested?
zanamivir aqueous solution
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
202 participants
Where
110 sitesin 13 countries
Study dates
Nov 2009to Feb 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 months and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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
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  • 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 locations and contacts

110 sites in 13 countries.

110 sites in 13 countries

United States40 sites

  • GSK Investigational Site

    Atlanta, Georgia, 30322

  • GSK Investigational Site

    Birmingham, Alabama, 35233

  • GSK Investigational Site

    Boston, Massachusetts, 02115-5724

  • GSK Investigational Site

    Boston, Massachusetts, 02115

  • GSK Investigational Site

    Butte, Montana, 59701

  • GSK Investigational Site

    Camden, New Jersey, 08103

  • GSK Investigational Site

    Chapel Hill, North Carolina, 27514

  • GSK Investigational Site

    Charlotte, North Carolina, 28203

  • GSK Investigational Site

    Cleveland, Ohio, 44106

  • GSK Investigational Site

    Columbus, Ohio, 43205

  • GSK Investigational Site

    Dallas, Texas, 75231

  • GSK Investigational Site

    Dallas, Texas, 75235

  • GSK Investigational Site

    Decatur, Georgia, 30033

  • GSK Investigational Site

    Fort Worth, Texas, 76104

  • GSK Investigational Site

    Gainesville, Florida, 32608

  • GSK Investigational Site

    Houston, Texas, 77030

  • GSK Investigational Site

    Indianapolis, Indiana, 46202

  • GSK Investigational Site

    Kansas City, Missouri, 64108

  • GSK Investigational Site

    Little Rock, Arkansas, 72202

  • GSK Investigational Site

    Louisville, Kentucky, 40202

  • GSK Investigational Site

    Memphis, Tennessee, 38103

  • GSK Investigational Site

    Memphis, Tennessee, 38105

  • GSK Investigational Site

    Milwaukee, Wisconsin, 53201

  • GSK Investigational Site

    New Hyde Park, New York, 11040

  • GSK Investigational Site

    New Orleans, Louisiana, 70112

  • GSK Investigational Site

    Philadelphia, Pennsylvania, 19102

  • GSK Investigational Site

    Phoenix, Arizona, 85023

  • GSK Investigational Site

    Pittsburgh, Pennsylvania, 15224

  • GSK Investigational Site

    Portland, Oregon, 97239

  • GSK Investigational Site

    Richmond, Virginia, 23249

  • GSK Investigational Site

    Saint Paul, Minnesota, 55102

  • GSK Investigational Site

    Salt Lake City, Utah, 84113

  • GSK Investigational Site

    San Diego, California, 92123

  • GSK Investigational Site

    St Louis, Missouri, 63110

  • GSK Investigational Site

    Stamford, Connecticut, 06902

  • GSK Investigational Site

    Tampa, Florida, 33606

  • GSK Investigational Site

    Toledo, Ohio, 43606

  • GSK Investigational Site

    Topeka, Kansas, 66604

  • GSK Investigational Site

    Washington D.C., District of Columbia, 20007

  • GSK Investigational Site

    Washington D.C., District of Columbia, 20010

Other trials in United States

United Kingdom12 sites

  • GSK Investigational Site

    Bristol, BS2 8AE

  • GSK Investigational Site

    Bristol, BS2 8HW

  • GSK Investigational Site

    Cardiff, CF14 4XW

  • GSK Investigational Site

    Glasgow, Lanarkshire, G11 6NT

  • GSK Investigational Site

    Leeds, LS1 3EX

  • GSK Investigational Site

    Leicester, LE1 5WW

  • GSK Investigational Site

    Leicester, LE3 9QP

  • GSK Investigational Site

    Liverpool, Merseyside, L7 8XP

  • GSK Investigational Site

    Livingston, West Lothian, EH54 6PP

  • GSK Investigational Site

    London, NW1 2BU

  • GSK Investigational Site

    Oxford, OX3 9DU

  • GSK Investigational Site

    Southampton, SO16 6YD

Other trials in United Kingdom

Spain11 sites

  • GSK Investigational Site

    (Móstoles) Madrid, 28935

  • GSK Investigational Site

    Badalona, 08916

  • GSK Investigational Site

    Barcelona, 08003

  • GSK Investigational Site

    Barcelona, 08035

  • GSK Investigational Site

    Barcelona, 08036

  • GSK Investigational Site

    Getafe/Madrid, 28905

  • GSK Investigational Site

    L'Hospitalet de Llobregat, 08907

  • GSK Investigational Site

    Madrid, 28007

  • GSK Investigational Site

    Madrid, 28034

  • GSK Investigational Site

    Madrid, 28041

  • GSK Investigational Site

    Madrid, 28046

Other trials in Spain

France10 sites

  • GSK Investigational Site

    Bron, 69677

  • GSK Investigational Site

    Grenoble, 38043

  • GSK Investigational Site

    Limoges, 87042

  • GSK Investigational Site

    Nancy, 54035

  • GSK Investigational Site

    Nice, 06200

  • GSK Investigational Site

    Nîmes, 30029

  • GSK Investigational Site

    Orléans, 45067

  • GSK Investigational Site

    Paris, 75018

  • GSK Investigational Site

    Paris, 75679

  • GSK Investigational Site

    Tours, 37044

Other trials in France

Australia8 sites

  • GSK Investigational Site

    Adelaide, South Australia, 5000

  • GSK Investigational Site

    Bedford Park, South Australia, 5043

  • GSK Investigational Site

    Chermside, Queensland, 4032

  • GSK Investigational Site

    Garran, Australian Capital Territory, 2606

  • GSK Investigational Site

    Heidelberg, Victoria, 3084

  • GSK Investigational Site

    Herston, Queensland, 4029

  • GSK Investigational Site

    Perth, Western Australia, 6000

  • GSK Investigational Site

    Subiaco, Western Australia, 6008

Other trials in Australia

Canada7 sites

  • GSK Investigational Site

    Chicoutimi, Quebec, G7H 5H6

  • GSK Investigational Site

    Halifax, Nova Scotia, B3K 6R8

  • GSK Investigational Site

    Montreal, Quebec, H1T 2M4

  • GSK Investigational Site

    Montreal, Quebec, H3T 1C5

  • GSK Investigational Site

    Québec, Quebec, G1V 4G2

  • GSK Investigational Site

    Toronto, Ontario, M5G 1X5

  • GSK Investigational Site

    Winnipeg, Manitoba, R3E 0J9

Other trials in Canada

South Africa7 sites

  • GSK Investigational Site

    Bellville, 7530

  • GSK Investigational Site

    Middelburg, Mpumalanga, 1055

  • GSK Investigational Site

    Observatory, 7925

  • GSK Investigational Site

    Panorama, 7500

  • GSK Investigational Site

    Rondebosch, 7700

  • GSK Investigational Site

    Tygerberg, 7505

  • GSK Investigational Site

    Worcester, 6850

Other trials in South Africa

Japan6 sites

  • GSK Investigational Site

    Fukuoka, 830-8543

  • GSK Investigational Site

    Hokkaido, 062-0931

  • GSK Investigational Site

    Kanagawa, 247-8533

  • GSK Investigational Site

    Osaka, 534-0021

  • GSK Investigational Site

    Osaka, 596-8522

  • GSK Investigational Site

    Yamanashi, 400-8506

Other trials in Japan

Brazil2 sites

  • GSK Investigational Site

    Rio de Janeiro, Rio de Janeiro, 21941-590

  • GSK Investigational Site

    São Paulo, São Paulo, 01308060

Other trials in Brazil

Norway2 sites

  • GSK Investigational Site

    Bergen, 5021

  • GSK Investigational Site

    Trondheim, 7030

Other trials in Norway

Russia2 sites

  • GSK Investigational Site

    Smolensk, 214006

  • GSK Investigational Site

    Yekaterinburg, 620102

Other trials in Russia

Thailand2 sites

  • GSK Investigational Site

    Bangkok, 10330

  • GSK Investigational Site

    Bangkok, 10700

Other trials in Thailand

Hong Kong1 site

  • GSK Investigational Site

    Shatin

Other trials in Hong Kong

About this study

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

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.

Read the 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 (>/= 18 years of age) with normal renal function will receive 600mg per dose. Pediatric (6 months to <13 years)/adolescent (>13 years to <18 years) subjects will receive an age-adjusted, weight-based dose (not to exceed the 600 mg adult 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 and renal replacement modality.

Serum pharmacokinetic assessments will be performed in subjects across all age groups 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.

Being tested
zanamivir aqueous solution
Keywords
pandemic, seasonal influenza, Influenza B virus, H1N1, zanamivir, Influenza A virus, H1N1 Subtype, Relenza, influenza, neuraminidase inhibitor
Medical subject headings
Influenza, Human

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • zanamivir aqueous solutionDrug

    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.

Study groups in NCT01014988
Study groupRoleWhat they receive
Single ArmOtherA 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.
Receives: Drug: zanamivir aqueous solution

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Any Adverse Event (AE) Considered to be Related to Study Treatment

    An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. All AEs were assesed by the Investigateor as related or not related to the study treatment.

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

  2. Number of Participants With Any Severe or Grade 3/4 AEs

    An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. AEs that occured during the study were evaluated by the Investigator and graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) table for grading the severity of adult and pediatric AEs. Grade 3=severe; Grade 4=potentially life threatening.

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

  3. Number of Participants With Any Severe or Grade 3/4 Treatment-related AE

    An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. AEs that occured during the study were evaluated by the Investigator and graded according to the DAIDS table for grading the severity of adult and pediatric AEs. Grade 3=severe; Grade 4=potentially life threatening. All AEs were assesed by the Investigateor as related or not related to the study treatment.

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

  4. Number of Participants Who Permanently Discontinued the Study Treatment Due to an AE

    An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.

    Measured: Up to 10 days

  5. Number of Participants Who Were Permanently Discontinued From the Study Due to an AE

    An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.

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

  6. Number of Participants With the Indicated Clinical Chemistry Values Relative to the Normal Range at Baseline (Day 1) and Day 5

    Blood samples for laboratory assessments were collected at Baseline (Day [D] 1), Days 3 and 5, and on post-treatment +2 days (if hospitalized) and post-treatment +23 days. Clinical chemistry parameters included alanine aminotransferase (ALT), direct bilirubin (DB), total bilirubin (TB), and creatinine. The number of participants with values that were high (H)/normal (N)/low (L) relative to the normal range at Baseline (D 1) and D 5 for the indicated clinical chemistry parameters are summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

    Measured: Baseline (Day 1) and Day 5

  7. Number of Participants With the Indicated Hematology Values Relative to the Normal Range at Baseline (Day 1) and Day 5

    Blood samples for laboratory assessments were collected at Baseline (Day [D] 1), Days 3 and 5, and on post-treatment +2 days (if hospitalized) and post-treatment +23 days. Hematology parameters included hemoglobin, total neutrophils (TN), and white blood cell (WBC) count. The number of participants with values that were high (H)/normal (N)/low (L) relative to the normal range at Baseline (D 1) and D 5 for the indicated hematology parameters are summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

    Measured: Baseline (Day 1) and Day 5

  8. Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Toxicities

    A toxicity was considered to be TE if it was greater than the Baseline grade, and if it had developed or increased post-Baseline in intensity (and prior to the last dose of investigational product). Clinical chemistry parameters included ALT, TB, and creatinine. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade 3=severe and Grade 4=potentially life threatening. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

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

  9. Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities

    A toxicity was considered to be TE if it was greater than the Baseline grade, and if it had developed or increased post-Baseline in intensity (and prior to the last dose of investigational product). The hematology parameters included hemoglobin, TN, and WBC count. Per the DAIDS table for grading the severity of adult and pediatric AEs, Grade 3=severe and Grade 4=potentially life threatening. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

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

  10. Median Heart Rate at Baseline (Day 1) and Day 5

    Heart rate was measured at Baseline (Day 1); Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. Heart rate was assessed once daily during inpatient or outpatient follow-up visits. Heart rate values at Baseline (Day 1) and Day 5 are summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles).

    Measured: Baseline (Day 1) and Day 5

  11. Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5

    SBP and DBP were measured at Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. SBP and DBP were assessed once daily during inpatient or outpatient follow-up visits. SBP and DBP values at Baseline (Day 1) and Day 5 are summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles).

    Measured: Baseline (Day 1) and Day 5

  12. Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5

    TCPO2 is a noninvasive test that directly measures the oxygen level of tissue beneath the skin. Because oxygen is carried to tissues by blood flow in the arteries, TCPO2 is an indirect measure of blood flow. The percent (%) oxygen saturation was measured at Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; and post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. Oxygen saturation was assessed once daily during inpatient follow-up visits. The median oxygen saturation values at Baseline (Day 1) and Day 5 are summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles).

    Measured: Baseline (Day 1) and Day 5

  13. Median Respiration Rate at Baseline (Day 1) and Day 5

    Respiration rate was measured at Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; and post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. Respiration rate was assessed once daily during inpatient or outpatient follow-up visits. The median respiration rate at Baseline (Day 1) and Day 5 is summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles).

    Measured: Baseline (Day 1) and Day 5

  14. Median Body Temperature at Baseline (Day 1) and Day 5

    Body temperature was recorded at Baseline (Day 1), Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; and post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. Body temperature was recorded once daily during inpatient or outpatient follow-up visits. Median body temperature at Baseline (Day 1) and Day 5 is summarized. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles).

    Measured: Baseline (Day 1) and Day 5

  15. Number of Participants Assessed as Normal/Abnormal (Clinically Significant [CS] and Not Clinically Significant [NCS]) for 12-lead Electrocardiogram (ECG) at Baseline (Day 1)

    The number of participants with an ECG status of normal and abnormal CS or NCS, as determined by the Investigator, is reported. Normal=all ECG parameters within the accepted normal ranges. Abnormal=ECG findings outside of normal ranges. CS=ECG with a CS abnormality that meets exclusion criteria. NCS=ECG with an abnormality that is not CS nor meets exclusion criteria, per Investigator, based on reasonable standards of clinical judgment. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X in the category titles).

    Measured: Baseline (Day 1)

  16. 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

    Twelve-lead ECGs were recorded for the parameters of QTcF and QTcB. The first set of pre-dose ECG values at Baseline (Day 1) and the pre-dose ECG values at Day 5 are presented. Baseline is defined as the last pre-treatment value collected. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X, X in the category titles). "NA" indicates that data are not available/analysis was not performed. Cohort 1 QTcF and QTcB minimum values of 0.0 were data entry errors that could not be addressed after Data Base Freeze.

    Measured: Baseline (Day 1) and Day 5

Secondary outcomes (18)

  1. Median Time to Virologic Improvement

    Time to virologic improvement is defined as a 2-log drop in viral load or undetectable viral ribonucleic acid (RNA) as measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) from nasopharyngeal samples (PCR positive at Baseline). Only those participants available at the specified time points were analyzed.

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

  2. Median Change From Baseline (Influenza A or B Quantitative PCR, as Appropriate) in Viral Load at the Indicated Time Points

    Change from Baseline in viral load was measured from nasopharyngeal swab samples, as determined by RT-PCR (PCR positive at Baseline). Nasopharyngeal swab samples were collected at Baseline (Day 1); Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10; and, only if the participants had continued symptoms and were hospitalized, post-treatment (PT) samples were collected at +2 days, +5 days, +9 days, +16 days, and +23 days. 'PT +23 days' also comprises viral load values at early study withdrawal. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X in the category titles). "NA" indicates that data are not available/analysis was not performed.

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

  3. Mean Viral Susceptibility to Zanamivir at Baseline (Day 1) and All Post-Baseline Visits Collectively

    Viral susceptibility to zanamivir at Baseline and at all post-Baseline visits collectively was assessed by neuraminidase (NA) enzyme inhibition assay. The mean IC50 data are summarized by subtype (A/H1N1, A/H3N2, B) and by visit. IC50 is defined as the concentration of zanamvir required to inhibit NA activity by 50%. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). "NA" indicates that data are not available/analysis was not performed. Please note: pediatric data are pending and will be updated when available.

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

  4. Number of Participants With Treatment-emergent (TE) Mutations

    Viral RNA isolated from participants at Baseline (Day 1) and post-Baseline visits were sequenced to determine the presence of TE neuraminidase (NA) and hemagglutinin (HA) mutations resulting from selective pressure. A mutation was considered to be TE if it was not present at Baseline and was present in the last post-Baseline sample analyzed.These mutations were classified as either known to confer zanamvir resistance or novel mutations with unknown clinical significance. Please note: pediatric data are pending and will be updated when available.

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

  5. Median Time to Resolution of Individual Vital Signs

    Times to return to afebrile status (normal body temperature), normal respiratory status, normal heart rate, and normal systolic blood pressure were assessed. Afebrile status is defined as a temperature <=36.6 axilla, <=37.2 oral, or <=37.7 rectal, core or typanic, degrees Centigrade. A return to normal respiratory status is defined as either: (a) return to pre-morbid oxygen requirement; or (b) return to no need for supplemental oxygen; or (c) respiratory rate <=60, <=40, <=34, <=30, <=24 or <=24 breaths/minute (without supplemental oxygen) for Cohorts 1-6 respectively . A normal HR is defined as <=160, <=150, <=140, <=120, <=100 or <=100 bpm for Cohorts 1-6 respectively, and a normal SBP is defined as >=70, >=74, >=76, >=80, >=90 or >=90 mmHg for Cohorts 1-6 respectively. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X, X, X in the category titles).

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

  6. Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation

    Ventilation status was measured at Baseline (Day 1); Days 2, 3, 4, 5, 6, 7, 8, 9, and 10; and post-treatment +2 days, +5 days, +9 days, +16 days (assessments to be done if participant remained hospitalized), and +23 days. Ventilation status was assessed once daily during inpatient follow-up visits. The number of participants reported for machine-assisted: extracorporeal membrane oxygenation (ECMO), endotracheal mechanical ventilation, and supplemental oxygen delivery (SOD) at "any time (AT) on study" and at Baseline (Day 1) are summarized.

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

  7. Duration of Mechanical Ventilation and Supplemental Oxygen Use

    Due to the conditional nature of data collection post treatment, the duration of mechanical ventilation and supplemental oxygen use were not determined.

    Measured: Up to discharge from the hospital

  8. Median Time to Return to Pre-morbid Functional Status

    Time to return to pre-morbid functional status was assessed on a 3-point scale (bed rest, limited ambulation, or unrestricted). Only those participants available at the specified time points were analyzed.

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

  9. Number of Participants With the Indicated Mortality Status at Day 14 and Day 28

    The number of participants who died on or before Study Day 14 and Study Day 28 was summarized. Only those participants available at the specified time points were analyzed.

    Measured: Day 14 and Day 28

  10. Median Time to Clinical Response (Sustained Resolution) of All Vital Signs (Composite)

    Sustained resolution of the following vital signs (composite) was assessed: afebrile status, normal oxygen saturation, normal respiratory status, normal HR, and normal BP. Clinical response is defined as the resolution of at least four of five vital signs within the following resolution criteria, maintained for 24 hours or hospital discharge, whichever occurred first: Temperature in degrees Centigrade (<=36.6 axilla, <=37.2 oral, <=37.7 rectal, core or tympanic); oxygen saturation (>=95%, without supplemental oxygen); respiratory status (return to pre-morbid oxygen requirement, or no need for supplemental oxygen, or respiratory rate <=60, <=40, <=34, <=30, <=24 or <=24 breaths/minute without supplemental oxygen for Cohorts 1-6 respectively); HR (<=160, <=150, <=140, <=120, <=100 or <=100 bpm for Cohorts 1-6 respectively); SBP (>=70, >=74, >=76, >=80, >=90 or >=90 mmHg for Cohorts 1-6 respectively). Only those participants available at the specified time points were analyzed.

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

  11. Number of Participants With Any AE Categorized as an Influenza Complication

    An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.

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

  12. Number of Participants Who Used Any Concomitant Antibiotic Medications for Complications of Influenza

    Concomitant medications (prescription and non-prescription) were permitted during the course of the study at the Investigator's discretion (except for prohibited medications: during the treatment period with IV zanamivir, other influenza antiviral drugs were not permitted). The number of participants who were treated with antibiotics for influenza complications was summarized.

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

  13. Median Duration of Hospitalization and Intensive Care Unit (ICU) Stays

    The duration of hospitalization (H) reflects the number of hospitalization days between the date of the first dose of investigational product and the date of discharge. ICU stay includes total duration in ICU and may include days in ICU before entry into the study. For participants with a missing discharge date who were not discharged at the end of the study, the date of discharge was imputed to the last follow-up visit (post-treatment +23 days). Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

    Measured: Up to discharge from hospital

  14. Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion

    The Cmax of zanamivir was evaluated at the end of infusion. Serial blood samples for pharmacokinetic (PK) analysis were collected if possible in conjunction with the initial dose on Day 1 (5-7 serial samples) and over a dosing interval during repeat dosing on Days 3, 4, or 5 (5 serial samples). PK data for all participants with available blood samples were analyzed. PK data for those participants who were neither on extracorporeal membrane oxygenation (ECMO) nor on continuous renal replacement therapy (CRRT), who were with CLcr >=80 mL/minutes (>=80mL/minute/1.73m^2 for cohorts 1-4) and who received an initial dose (ID) and a maintenance dose (MD) of 14 mg/kg (6 months to <6 years of age), 12 mg/kg, not to exceed 600 mg (6 to <18 years of age) or 600 mg zanamivir (>=18 years of age) (represented by n=X in the category titles) were summarized. "NA" indicates that data are not available/analysis was not performed.

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

  15. 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

    The AUC(0-tau) during the repeat dose interval and AUC(0-inf) for the initial dose were evaluated. Serial blood samples for PK analysis were collected if possible in conjunction with the initial dose on Day 1 (5-7 serial samples) and over a dosing interval during repeat dosing on Days 3, 4, or 5 (5 serial samples). PK data for all participants with available blood samples were analyzed. PK data for those participants with a CLcr >=80 mL/minutes (>=80 mL/minute/1.73m^2 for cohorts 1-4) and who received an ID and a MD of 14 mg/kg (6 months to <6 years of age), 12 mg/kg, not to exceed 600 mg (6 to <18 years of age) or 600 mg zanamivir (>=18 years of age) (represented by n=X in the category titles) were summarized. "NA" indicates that data are not available/analysis was not performed.

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

  16. Geometric Mean Terminal Half Life (t1/2) of Zanamivir

    The t1/2 of zanamivir was evaluated. Terminal half life is defined as the time it takes for a substance to lose half of its pharmacologic, physiologic, or radiologic activity. Serial blood samples for PK analysis were collected if possible in conjunction with the initial dose on Day 1 (5-7 serial samples) and over a dosing interval during repeat dosing on Day 3, 4, or 5 (5 serial samples). PK data for all participants with available blood samples were analyzed. PK data for those participants with a CLcr>=80 mL/minutes (>=80 mL/minute/1.73m^2 for cohorts 1-4) and who received an ID and a MD of 14 mg/kg (6 months to <6 years of age), 12 mg/kg, not to exceed 600 mg (6 to <18 years of age) or 600 mg zanamivir (>=18 years of age) (represented by n=X in the category titles) were summarized. "NA" indicates that data are not available/analysis was not performed.

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

  17. Geometric Mean Serum Clearance of Zanamivir

    The serum clearance of zanamivir was evaluated. Clearance is defined as the volume of zanamivir per unit time eliminated from serum. Serial blood samples for PK analysis were collected if possible in conjunction with the initial dose on Day 1 (5-7 serial samples) and over a dosing interval during repeat dosing on Days 3, 4, or 5 (5 serial samples). PK data for all participants with available blood samples were analyzed. PK data for those participants with a CLcr >=80 mL/minutes (>=80 mL/minute/1.73m^2 for cohorts 1-4) and who received an ID and a MD 14 mg/kg (6 months to <6 years of age), 12 mg/kg, not to exceed 600 mg (6 to <18 years of age) or 600 mg zanamivir (>=18 years of age) (represented by n=X in the category titles) were summarized. "NA" indicates that data are not available/analysis was not performed.

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

  18. Geometric Mean Volume of Distribution (Vd) of Zanamivir

    The Vd of zanamivir was evaluated. Volume of distribution is defined as the apparent volume in which zanamivir is distributed. Serial blood samples for PK analysis were collected if possible in conjunction with the initial dose on Day 1 (5-7 serial samples) and over a dosing interval during repeat dosing on Days 3, 4, or 5 (5 serial samples). PK data for all participants with available blood samples were analyzed. PK data for those participants with a CLcr >= 80 mL/minutes (>=80 mL/minute/1.73m^2 for cohorts 1-4) and who received an ID and a MD of 14 mg/kg (6 months to <6 years of age), 12 mg/kg, not to exceed 600 mg (6 to <18 years of age) or 600 mg zanamivir (>=18 years of age) (represented by n=X in the category titles) were summarized. "NA" indicates that data are not available/analysis was not performed.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Nov 2009 (estimated)
  2. Study startNov 2009
  3. Primary completionFeb 2015
  4. Study completionFeb 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
202 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01014988
Sponsor's protocol ID
113678
Status last verified
Jan 2017
First submitted
16 Nov 2009
Last updated
28 Mar 2017
Data monitoring committee
Yes
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

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.

    PubMed 23983212

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing zanamivir aqueous solution in people with Influenza, Human, run by GlaxoSmithKline at 110 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 110 sites in United States, United Kingdom, Spain, France, Australia and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Any Adverse Event (AE) Considered to be Related to Study Treatment (time frame: Up to post-treatment (PT) + 23 days). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01014988, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2017.

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