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

8. února 2017 aktualizováno: GlaxoSmithKline

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.

Přehled studie

Postavení

Dokončeno

Podmínky

Intervence / Léčba

Detailní popis

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.

Typ studie

Intervenční

Zápis (Aktuální)

202

Fáze

  • Fáze 2

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

  • Austrálie
    • Australian Capital Territory
      • Garran, Australian Capital Territory, Austrálie, 2606
        • GSK Investigational Site
    • Queensland
      • Chermside, Queensland, Austrálie, 4032
        • GSK Investigational Site
      • Herston, Queensland, Austrálie, 4029
        • GSK Investigational Site
    • South Australia
      • Adelaide, South Australia, Austrálie, 5000
        • GSK Investigational Site
      • Bedford Park, South Australia, Austrálie, 5043
        • GSK Investigational Site
    • Victoria
      • Heidelberg, Victoria, Austrálie, 3084
        • GSK Investigational Site
    • Western Australia
      • Perth, Western Australia, Austrálie, 6000
        • GSK Investigational Site
      • Subiaco, Western Australia, Austrálie, 6008
        • GSK Investigational Site
  • Brazílie
      • Rio de Janeiro, Brazílie, 21941-590
        • GSK Investigational Site
    • São Paulo
      • Sao Paulo, São Paulo, Brazílie, 01308060
        • GSK Investigational Site
  • Francie
      • Bron cedex, Francie, 69677
        • GSK Investigational Site
      • Grenoble cedex 9, Francie, 38043
        • GSK Investigational Site
      • Limoges cedex, Francie, 87042
        • GSK Investigational Site
      • Nancy cedex, Francie, 54035
        • GSK Investigational Site
      • Nice, Francie, 06200
        • GSK Investigational Site
      • Nîmes cedex 9, Francie, 30029
        • GSK Investigational Site
      • Orléans cedex 2, Francie, 45067
        • GSK Investigational Site
      • Paris, Francie, 75018
        • GSK Investigational Site
      • Paris cedex 14, Francie, 75679
        • GSK Investigational Site
      • Tours cedex 9, Francie, 37044
        • GSK Investigational Site
  • Hongkong
      • Shatin, Hongkong
        • GSK Investigational Site
  • Japonsko
      • Fukuoka, Japonsko, 830-8543
        • GSK Investigational Site
      • Hokkaido, Japonsko, 062-0931
        • GSK Investigational Site
      • Kanagawa, Japonsko, 247-8533
        • GSK Investigational Site
      • Osaka, Japonsko, 534-0021
        • GSK Investigational Site
      • Osaka, Japonsko, 596-8522
        • GSK Investigational Site
      • Yamanashi, Japonsko, 400-8506
        • GSK Investigational Site
  • Jižní Afrika
      • Bellville, Jižní Afrika, 7530
        • GSK Investigational Site
      • Observatory, Jižní Afrika, 7925
        • GSK Investigational Site
      • Panorama, Jižní Afrika, 7500
        • GSK Investigational Site
      • Rondebosch, Jižní Afrika, 7700
        • GSK Investigational Site
      • Tygerberg, Jižní Afrika, 7505
        • GSK Investigational Site
      • Worcester, Jižní Afrika, 6850
        • GSK Investigational Site
    • Mpumalanga
      • Middelburg, Mpumalanga, Jižní Afrika, 1055
        • GSK Investigational Site
  • Kanada
      • Quebec, Kanada, G1V 4G2
        • GSK Investigational Site
    • Manitoba
      • Winnipeg, Manitoba, Kanada, R3E 0J9
        • GSK Investigational Site
    • Nova Scotia
      • Halifax, Nova Scotia, Kanada, B3K 6R8
        • GSK Investigational Site
    • Ontario
      • Toronto, Ontario, Kanada, M5G 1X5
        • GSK Investigational Site
    • Quebec
      • Chicoutimi, Quebec, Kanada, G7H 5H6
        • GSK Investigational Site
      • Montreal, Quebec, Kanada, H1T 2M4
        • GSK Investigational Site
      • Montreal, Quebec, Kanada, H3T 1C5
        • GSK Investigational Site
  • Norsko
      • Bergen, Norsko, 5021
        • GSK Investigational Site
      • Trondheim, Norsko, 7030
        • GSK Investigational Site
  • Ruská Federace
      • Ekaterinburg, Ruská Federace, 620102
        • GSK Investigational Site
      • Smolensk, Ruská Federace, 214006
        • GSK Investigational Site
  • Spojené království
      • Bristol, Spojené království, BS2 8HW
        • GSK Investigational Site
      • Bristol, Spojené království, BS2 8AE
        • GSK Investigational Site
      • Cardiff, Spojené království, CF14 4XW
        • GSK Investigational Site
      • Leeds, Spojené království, LS1 3EX
        • GSK Investigational Site
      • Leicester, Spojené království, LE1 5WW
        • GSK Investigational Site
      • Leicester, Spojené království, LE3 9QP
        • GSK Investigational Site
      • London, Spojené království, NW1 2BU
        • GSK Investigational Site
      • Oxford, Spojené království, OX3 9DU
        • GSK Investigational Site
      • Southampton, Spojené království, SO16 6YD
        • GSK Investigational Site
    • Lanarkshire
      • Glasgow, Lanarkshire, Spojené království, G11 6NT
        • GSK Investigational Site
    • Merseyside
      • Liverpool, Merseyside, Spojené království, L7 8XP
        • GSK Investigational Site
    • West Lothian
      • Livingston, West Lothian, Spojené království, EH54 6PP
        • GSK Investigational Site
  • Spojené státy
    • Alabama
      • Birmingham, Alabama, Spojené státy, 35233
        • GSK Investigational Site
    • Arizona
      • Phoenix, Arizona, Spojené státy, 85023
        • GSK Investigational Site
    • Arkansas
      • Little Rock, Arkansas, Spojené státy, 72202
        • GSK Investigational Site
    • California
      • San Diego, California, Spojené státy, 92123
        • GSK Investigational Site
    • Connecticut
      • Stamford, Connecticut, Spojené státy, 06902
        • GSK Investigational Site
    • District of Columbia
      • Washington, District of Columbia, Spojené státy, 20007
        • GSK Investigational Site
      • Washington, District of Columbia, Spojené státy, 20010
        • GSK Investigational Site
    • Florida
      • Gainesville, Florida, Spojené státy, 32608
        • GSK Investigational Site
      • Tampa, Florida, Spojené státy, 33606
        • GSK Investigational Site
    • Georgia
      • Atlanta, Georgia, Spojené státy, 30322
        • GSK Investigational Site
      • Decatur, Georgia, Spojené státy, 30033
        • GSK Investigational Site
    • Indiana
      • Indianapolis, Indiana, Spojené státy, 46202
        • GSK Investigational Site
    • Kansas
      • Topeka, Kansas, Spojené státy, 66604
        • GSK Investigational Site
    • Kentucky
      • Louisville, Kentucky, Spojené státy, 40202
        • GSK Investigational Site
    • Louisiana
      • New Orleans, Louisiana, Spojené státy, 70112
        • GSK Investigational Site
    • Massachusetts
      • Boston, Massachusetts, Spojené státy, 02115
        • GSK Investigational Site
      • Boston, Massachusetts, Spojené státy, 02115-5724
        • GSK Investigational Site
    • Minnesota
      • St. Paul, Minnesota, Spojené státy, 55102
        • GSK Investigational Site
    • Missouri
      • Kansas City, Missouri, Spojené státy, 64108
        • GSK Investigational Site
      • St. Louis, Missouri, Spojené státy, 63110
        • GSK Investigational Site
    • Montana
      • Butte, Montana, Spojené státy, 59701
        • GSK Investigational Site
    • New Jersey
      • Camden, New Jersey, Spojené státy, 08103
        • GSK Investigational Site
    • New York
      • New Hyde Park, New York, Spojené státy, 11040
        • GSK Investigational Site
    • North Carolina
      • Chapel Hill, North Carolina, Spojené státy, 27514
        • GSK Investigational Site
      • Charlotte, North Carolina, Spojené státy, 28203
        • GSK Investigational Site
    • Ohio
      • Cleveland, Ohio, Spojené státy, 44106
        • GSK Investigational Site
      • Columbus, Ohio, Spojené státy, 43205
        • GSK Investigational Site
      • Toledo, Ohio, Spojené státy, 43606
        • GSK Investigational Site
    • Oregon
      • Portland, Oregon, Spojené státy, 97239
        • GSK Investigational Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, Spojené státy, 19102
        • GSK Investigational Site
      • Pittsburgh, Pennsylvania, Spojené státy, 15224
        • GSK Investigational Site
    • Tennessee
      • Memphis, Tennessee, Spojené státy, 38105
        • GSK Investigational Site
      • Memphis, Tennessee, Spojené státy, 38103
        • GSK Investigational Site
    • Texas
      • Dallas, Texas, Spojené státy, 75231
        • GSK Investigational Site
      • Dallas, Texas, Spojené státy, 75235
        • GSK Investigational Site
      • Fort Worth, Texas, Spojené státy, 76104
        • GSK Investigational Site
      • Houston, Texas, Spojené státy, 77030
        • GSK Investigational Site
    • Utah
      • Salt Lake City, Utah, Spojené státy, 84113
        • GSK Investigational Site
    • Virginia
      • Richmond, Virginia, Spojené státy, 23249
        • GSK Investigational Site
    • Wisconsin
      • Milwaukee, Wisconsin, Spojené státy, 53201
        • GSK Investigational Site
  • Thajsko
      • Bangkok, Thajsko, 10330
        • GSK Investigational Site
      • Bangkok, Thajsko, 10700
        • GSK Investigational Site
  • Španělsko
      • (Móstoles) Madrid, Španělsko, 28935
        • GSK Investigational Site
      • Badalona, Španělsko, 08916
        • GSK Investigational Site
      • Barcelona, Španělsko, 08036
        • GSK Investigational Site
      • Barcelona, Španělsko, 08035
        • GSK Investigational Site
      • Barcelona, Španělsko, 08003
        • GSK Investigational Site
      • Getafe/Madrid, Španělsko, 28905
        • GSK Investigational Site
      • L'Hospitalet de Llobregat, Španělsko, 08907
        • GSK Investigational Site
      • Madrid, Španělsko, 28041
        • GSK Investigational Site
      • Madrid, Španělsko, 28007
        • GSK Investigational Site
      • Madrid, Španělsko, 28046
        • GSK Investigational Site
      • Madrid, Španělsko, 28034
        • GSK Investigational Site

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

6 měsíců a starší (Dítě, Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

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.

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.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: N/A
  • Intervenční model: Přiřazení jedné skupiny
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Jiný: 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.
Lék: 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.

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Number of Participants With Any Adverse Event (AE) Considered to be Related to Study Treatment
Časové okno: Up to post-treatment (PT) + 23 days
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.
Up to post-treatment (PT) + 23 days
Number of Participants With Any Severe or Grade 3/4 AEs
Časové okno: Up to post-treatment (PT) + 23 days
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.
Up to post-treatment (PT) + 23 days
Number of Participants With Any Severe or Grade 3/4 Treatment-related AE
Časové okno: Up to post-treatment (PT) + 23 days
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.
Up to post-treatment (PT) + 23 days
Number of Participants Who Permanently Discontinued the Study Treatment Due to an AE
Časové okno: Up to 10 days
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.
Up to 10 days
Number of Participants Who Were Permanently Discontinued From the Study Due to an AE
Časové okno: Up to post-treatment (PT) + 23 days
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.
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
Časové okno: 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).
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
Časové okno: 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).
Baseline (Day 1) and Day 5
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Clinical Chemistry Toxicities
Časové okno: Up to post-treatment (PT) + 23 days
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).
Up to post-treatment (PT) + 23 days
Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Hematology Toxicities
Časové okno: Up to post-treatment (PT) + 23 days
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).
Up to post-treatment (PT) + 23 days
Median Heart Rate at Baseline (Day 1) and Day 5
Časové okno: 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).
Baseline (Day 1) and Day 5
Median Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Baseline (Day 1) and Day 5
Časové okno: 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).
Baseline (Day 1) and Day 5
Median Oxygen Saturation Measured Via Transcutaneous Oximetry (TCPO2) at Baseline (Day 1) and Day 5
Časové okno: 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).
Baseline (Day 1) and Day 5
Median Respiration Rate at Baseline (Day 1) and Day 5
Časové okno: 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).
Baseline (Day 1) and Day 5
Median Body Temperature at Baseline (Day 1) and Day 5
Časové okno: 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).
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)
Časové okno: 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).
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
Časové okno: 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.
Baseline (Day 1) and Day 5

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Median Time to Virologic Improvement
Časové okno: Up to post-treatment (PT) + 23 days
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.
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
Časové okno: Baseline (Day 1); Days 2, 3, 4, 5, 7, and 10; and post-treatment +2, +5, +9, +16, +23 days
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.
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
Časové okno: Baseline and up to post-treatment (PT) + 23 days
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.
Baseline and up to post-treatment (PT) + 23 days
Number of Participants With Treatment-emergent (TE) Mutations
Časové okno: Baseline and up to post-treatment (PT) + 23 days
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.
Baseline and up to post-treatment (PT) + 23 days
Median Time to Resolution of Individual Vital Signs
Časové okno: Up to post-treatment (PT) + 23 days
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).
Up to post-treatment (PT) + 23 days
Number of Participants With the Indicated Ventilation Status: Modality of Supplemental Oxygen Delivery and Mechanical Ventilation
Časové okno: Up to post-treatment (PT) + 23 days
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.
Up to post-treatment (PT) + 23 days
Duration of Mechanical Ventilation and Supplemental Oxygen Use
Časové okno: Up to discharge from the hospital
Due to the conditional nature of data collection post treatment, the duration of mechanical ventilation and supplemental oxygen use were not determined.
Up to discharge from the hospital
Median Time to Return to Pre-morbid Functional Status
Časové okno: Up to post-treatment (PT) + 23 days
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.
Up to post-treatment (PT) + 23 days
Number of Participants With the Indicated Mortality Status at Day 14 and Day 28
Časové okno: 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.
Day 14 and Day 28
Median Time to Clinical Response (Sustained Resolution) of All Vital Signs (Composite)
Časové okno: Up to post-treatment (PT) + 23 days
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.
Up to post-treatment (PT) + 23 days
Number of Participants With Any AE Categorized as an Influenza Complication
Časové okno: Up to post-treatment (PT) + 23 days
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.
Up to post-treatment (PT) + 23 days
Number of Participants Who Used Any Concomitant Antibiotic Medications for Complications of Influenza
Časové okno: Up to post-treatment (PT) + 23 days
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.
Up to post-treatment (PT) + 23 days
Median Duration of Hospitalization and Intensive Care Unit (ICU) Stays
Časové okno: Up to discharge from hospital
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).
Up to discharge from hospital
Geometric Mean Maximum Serum Concentration (Cmax) of Zanamivir at the End of Infusion
Časové okno: Day 1 and Days 3, 4, or 5
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.
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
Časové okno: Day 1 and Days 3, 4, or 5
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.
Day 1 and Days 3, 4, or 5
Geometric Mean Terminal Half Life (t1/2) of Zanamivir
Časové okno: Day 1 and Days 3, 4, or 5
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.
Day 1 and Days 3, 4, or 5
Geometric Mean Serum Clearance of Zanamivir
Časové okno: Day 1 and Days 3, 4, or 5
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.
Day 1 and Days 3, 4, or 5
Geometric Mean Volume of Distribution (Vd) of Zanamivir
Časové okno: Day 1 and Days 3, 4, or 5
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.
Day 1 and Days 3, 4, or 5

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

GlaxoSmithKline

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Užitečné odkazy

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia

1. listopadu 2009

Primární dokončení (Aktuální)

1. února 2015

Dokončení studie (Aktuální)

1. února 2015

Termíny zápisu do studia

První předloženo

16. listopadu 2009

První předloženo, které splnilo kritéria kontroly kvality

16. listopadu 2009

První zveřejněno (Odhad)

17. listopadu 2009

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

28. března 2017

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

8. února 2017

Naposledy ověřeno

1. ledna 2017

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • 113678

Plán pro data jednotlivých účastníků (IPD)

Plánujete sdílet data jednotlivých účastníků (IPD)?

ANO

Popis plánu IPD

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Studijní data/dokumenty

  1. Plán statistické analýzy
    Identifikátor informace: 113678
    Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
  2. Protokol studie
    Identifikátor informace: 113678
    Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
  3. Zpráva o klinické studii
    Identifikátor informace: 113678
    Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
  4. Specifikace datové sady
    Identifikátor informace: 113678
    Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
  5. Soubor dat jednotlivých účastníků
    Identifikátor informace: 113678
    Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
  6. Formulář komentované zprávy o případu
    Identifikátor informace: 113678
    Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
  7. Formulář informovaného souhlasu
    Identifikátor informace: 113678
    Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

Klinické studie na Chřipka, člověk

Klinické studie na zanamivir aqueous solution

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Vzácné nemoci

Drogové intervence

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