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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01014988
First received: November 16, 2009
Last updated: August 7, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Influenza, Human
Drug: zanamivir aqueous solution
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Incidence of AEs, including AE considered to be related to study treatment, grade 3/4 or severe AEs and those treatment related, AEs leading to discontinuation of study drug or study, SAEs, treatment related SAEs, fatal events [ Time Frame: 33 days ] [ Designated as safety issue: Yes ]
  • Clinical chemistry and hematology data values outside the normal range, Clinical laboratory data summarized based on changes from baseline and toxicity shifts from baseline, treatment emergent toxicities [ Time Frame: 33 days ] [ Designated as safety issue: Yes ]
  • Heart rate, blood pressure, oxygen saturation, respiration rate and temperature will be summarized by visit, change from baseline of the vital signs will be summarized. [ Time Frame: 33 days ] [ Designated as safety issue: Yes ]
  • Number and percentage of subjects who had abnormal and/or clinically significant ECG findings. If available, ECG interval data and change from baseline, QTc interval will be calculated [ Time Frame: 33 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change in quantitative viral load over time and change from baseline measured from nasopharyngeal swab samples, as determined by quantitative virus culture (and retrospectively by RT-PCR, if available) [ Time Frame: 33 days ] [ Designated as safety issue: No ]
  • Time to no detectable viral RNA and to absence of cultivable virus in nasopharyngeal samples. [ Time Frame: 33 days ] [ Designated as safety issue: No ]
  • Proportion of subjects who are negative by virus culture (and RT-PCR if available) in nasopharyngeal samples [ Time Frame: Day 3 to 33 days ] [ Designated as safety issue: No ]
  • Viral susceptibility to zanamivir at baseline, and if virus present, at subsequent timepoints during the study, as assessed by NA sequence analysis and NA enzyme inhibition assay [ Time Frame: 33 days ] [ Designated as safety issue: No ]
  • Frequency of resistance emergence to zanamivir [ Time Frame: 33 days ] [ Designated as safety issue: No ]
  • Mortality rate at Day 14 and Day 28 [ Time Frame: 33 days ] [ Designated as safety issue: Yes ]
  • Incidence of complications of influenza and associated antibiotic use [ Time Frame: 33 days ] [ Designated as safety issue: Yes ]
  • Ventilation status: modality, duration of supplemental oxygen and of mechanical ventilation [ Time Frame: 33 days ] [ Designated as safety issue: Yes ]
  • Time to resolution of individual vital signs: afebrile status, return to normal respiratory status, return to normal heart rate, and time to return to normal systolic blood pressure [ Time Frame: 33 days ] [ Designated as safety issue: Yes ]
  • Length of total ICU stay and hospital stay as assessed from 1st day of dosing [ Time Frame: 33 days ] [ Designated as safety issue: No ]
  • Level of activity: Time to return to pre-morbid functional status as assessed on a 3 point scale (bed rest, limited ambulation or unrestricted) [ Time Frame: 33 days ] [ Designated as safety issue: No ]
  • Time to virologic improvement, defined as a 2-log drop in viral load or undetectable viral RNA as measured by quantitative RT-PCR from nasopharyngeal samples [ Time Frame: 33 days ] [ Designated as safety issue: No ]
  • Time to sustained resolution of all vital signs (composite): afebrile status, normal respiratory status, normal heart rate, and normal blood pressure [ Time Frame: 33 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: November 2009
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: 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.

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.

  Eligibility

Ages Eligible for Study:   6 Months and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female aged greater than or equal to 6 months of age; a female is eligible to enter and participate in the study if she is:

    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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01014988

Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

  Show 112 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01014988     History of Changes
Other Study ID Numbers: 113678
Study First Received: November 16, 2009
Last Updated: August 7, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Spain: Bernat Soria
Russia: Russian Ministry of Health
Thailand: Ministry of Public Health
Canada: Health Canada
France: Agence Française de Sécurité Sanitaire des Produits de Santé
United States: Institutional Review Board
Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
pandemic
seasonal influenza
Influenza B virus
H1N1
zanamivir
Influenza A virus, H1N1 Subtype
Relenza
influenza
neuraminidase inhibitor

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Pharmaceutical Solutions
Zanamivir
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 18, 2014