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

NCT ID: NCT01014988

Last Updated: 2017-03-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 202 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2015-02-28

Brief Summary

The purpose of this study is to determine whether zanamivir aqueous solution given by intravenous injection is safe in treating hospitalized patients with confirmed influenza infection. A single arm open-label design has been selected to achieve the primary objective of providing regulatory authorities with safety data on IV zanamivir.

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.

Conditions

Influenza, Human

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: OTHER

zanamivir aqueous solution

Intervention Type: DRUG

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.

Interventions

zanamivir aqueous solution

Zanamivir aqueous solution 10mg/mL is a clear, colorless, single use, sterile non-preserved preparation containing 10mg of zanamivir in each milliliter, and made isotonic with sodium chloride. It is presented in 20mL clear glass vials closed with rubber stoppers. Each vial contains 200mg of zanamivir.

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 6 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Birmingham, Alabama, United States

GSK Investigational Site

Phoenix, Arizona, United States

GSK Investigational Site

Little Rock, Arkansas, United States

GSK Investigational Site

San Diego, California, United States

GSK Investigational Site

Stamford, Connecticut, United States

GSK Investigational Site

Washington D.C., District of Columbia, United States

GSK Investigational Site

Washington D.C., District of Columbia, United States

GSK Investigational Site

Gainesville, Florida, United States

GSK Investigational Site

Tampa, Florida, United States

GSK Investigational Site

Atlanta, Georgia, United States

GSK Investigational Site

Decatur, Georgia, United States

GSK Investigational Site

Indianapolis, Indiana, United States

GSK Investigational Site

Topeka, Kansas, United States

GSK Investigational Site

Louisville, Kentucky, United States

GSK Investigational Site

New Orleans, Louisiana, United States

GSK Investigational Site

Boston, Massachusetts, United States

GSK Investigational Site

Boston, Massachusetts, United States

GSK Investigational Site

Saint Paul, Minnesota, United States

GSK Investigational Site

Kansas City, Missouri, United States

GSK Investigational Site

St Louis, Missouri, United States

GSK Investigational Site

Butte, Montana, United States

GSK Investigational Site

Camden, New Jersey, United States

GSK Investigational Site

New Hyde Park, New York, United States

GSK Investigational Site

Chapel Hill, North Carolina, United States

GSK Investigational Site

Charlotte, North Carolina, United States

GSK Investigational Site

Cleveland, Ohio, United States

GSK Investigational Site

Columbus, Ohio, United States

GSK Investigational Site

Toledo, Ohio, United States

GSK Investigational Site

Portland, Oregon, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

Pittsburgh, Pennsylvania, United States

GSK Investigational Site

Memphis, Tennessee, United States

GSK Investigational Site

Memphis, Tennessee, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Fort Worth, Texas, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

Salt Lake City, Utah, United States

GSK Investigational Site

Richmond, Virginia, United States

GSK Investigational Site

Milwaukee, Wisconsin, United States

GSK Investigational Site

Garran, Australian Capital Territory, Australia

GSK Investigational Site

Chermside, Queensland, Australia

GSK Investigational Site

Herston, Queensland, Australia

GSK Investigational Site

Adelaide, South Australia, Australia

GSK Investigational Site

Bedford Park, South Australia, Australia

GSK Investigational Site

Heidelberg, Victoria, Australia

GSK Investigational Site

Perth, Western Australia, Australia

GSK Investigational Site

Subiaco, Western Australia, Australia

GSK Investigational Site

Rio de Janeiro, Rio de Janeiro, Brazil

GSK Investigational Site

São Paulo, São Paulo, Brazil

GSK Investigational Site

Winnipeg, Manitoba, Canada

GSK Investigational Site

Halifax, Nova Scotia, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Chicoutimi, Quebec, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Québec, Quebec, Canada

GSK Investigational Site

Bron, , France

GSK Investigational Site

Grenoble, , France

GSK Investigational Site

Limoges, , France

GSK Investigational Site

Nancy, , France

GSK Investigational Site

Nice, , France

GSK Investigational Site

Nîmes, , France

GSK Investigational Site

Orléans, , France

GSK Investigational Site

Paris, , France

GSK Investigational Site

Paris, , France

GSK Investigational Site

Tours, , France

GSK Investigational Site

Shatin, , Hong Kong

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Hokkaido, , Japan

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Yamanashi, , Japan

GSK Investigational Site

Bergen, , Norway

GSK Investigational Site

Trondheim, , Norway

GSK Investigational Site

Smolensk, , Russia

GSK Investigational Site

Yekaterinburg, , Russia

GSK Investigational Site

Middelburg, Mpumalanga, South Africa

GSK Investigational Site

Bellville, , South Africa

GSK Investigational Site

Observatory, , South Africa

GSK Investigational Site

Panorama, , South Africa

GSK Investigational Site

Rondebosch, , South Africa

GSK Investigational Site

Tygerberg, , South Africa

GSK Investigational Site

Worcester, , South Africa

GSK Investigational Site

(Móstoles) Madrid, , Spain

GSK Investigational Site

Badalona, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Getafe/Madrid, , Spain

GSK Investigational Site

L'Hospitalet de Llobregat, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Bangkok, , Thailand

GSK Investigational Site

Bangkok, , Thailand

GSK Investigational Site

Glasgow, Lanarkshire, United Kingdom

GSK Investigational Site

Liverpool, Merseyside, United Kingdom

GSK Investigational Site

Livingston, West Lothian, United Kingdom

GSK Investigational Site

Bristol, , United Kingdom

GSK Investigational Site

Bristol, , United Kingdom

GSK Investigational Site

Cardiff, , United Kingdom

GSK Investigational Site

Leeds, , United Kingdom

GSK Investigational Site

Leicester, , United Kingdom

GSK Investigational Site

Leicester, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

Oxford, , United Kingdom

GSK Investigational Site

Southampton, , United Kingdom

Countries

United States; Australia; Brazil; Canada; France; Hong Kong; Japan; Norway; Russia; South Africa; Spain; Thailand; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 23983212 (View on PubMed)

Study Documents

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm100228.htm

FDA information on Influenza (Flu) antiviral drugs and related information

http://www.cdc.gov/flu/

Centers For Disease Control and Prevention seasonal flu information

Other Identifiers

113678

Identifier Type: -

Identifier Source: org_study_id