A Study of Intravenous Zanamivir Versus Oral Oseltamivir in Adults and Adolescents Hospitalized With Influenza (ZORO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01231620
First received: October 28, 2010
Last updated: March 27, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to test the safety and efficacy of zanamivir given intravenously and how well it works at two different doses in hospitalized adolescents and adults with flu. Zanamivir will be compared with oseltamivir, which is used for treating flu.


Condition Intervention Phase
Influenza, Human
Drug: 300mg intravenous (IV) zanamivir and oral oseltamivir placebo
Drug: 600mg intravenous (IV) zanamivir and oral oseltamivir placebo
Drug: 75mg oral oseltamivir and intravenous zanamivir placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III International, Randomized, Double-blind, Double-dummy Study to Evaluate the Efficacy and Safety of 300 mg or 600 mg of Intravenous Zanamivir Twice Daily Compared to 75 mg of Oral Oseltamivir Twice Daily in the Treatment of Hospitalized Adults and Adolescents With Influenza

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Time to clinical response in subjects with confirmed influenza treated with 300 mg or 600 mg IV zanamivir compared with 75 mg oral oseltamivir [ Time Frame: Up to 42 Days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in the Katz Index of Independence in Activities of Daily Living (ADL) score and time to return to pre-morbid level of activity [ Time Frame: Baseline up to 42 days ] [ Designated as safety issue: No ]
  • Mortality rate at Day 14 and Day 28 [ Time Frame: Day 14 and day 28 ] [ Designated as safety issue: No ]
  • Disease progression and complications of influenza [ Time Frame: Up to 42 days ] [ Designated as safety issue: No ]
  • Summary of ventilation status [ Time Frame: Up to 42 days ] [ Designated as safety issue: No ]
  • Duration of hospitalization and ICU (intense care unit) stay [ Time Frame: Up to 42 days ] [ Designated as safety issue: No ]
  • Time to improvement of vital signs [ Time Frame: Baseline up to 42 days ] [ Designated as safety issue: No ]
  • Time to reduction in viral load and percentage of patients with undetectable viral RNA obtained from upper and lower respiratory samples [ Time Frame: Baseline up to 42 days ] [ Designated as safety issue: No ]
  • Changes in viral susceptibility [ Time Frame: Baseline up to 42 days ] [ Designated as safety issue: No ]
  • Pharmacokinetics of IV Zanamivir as measured by minimum or maximum serum concentration [ Time Frame: Up to day 4 ] [ Designated as safety issue: No ]
  • Safety and tolerability as measured by the incidence of adverse events and laboratory abnormalities [ Time Frame: Up to 42 days ] [ Designated as safety issue: No ]
  • ECG(electrocardiogram) data [ Time Frame: Up to day 4 ] [ Designated as safety issue: No ]

Estimated Enrollment: 600
Study Start Date: January 2011
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intravenous (IV) Zanamivir 300mg Twice Daily
300mg of IV zanamivir infusion twice daily plus oral oseltamivir placebo twice daily
Drug: 300mg intravenous (IV) zanamivir and oral oseltamivir placebo
300mg IV zanamivir and oral oseltamivir placebo
Other Name: Relenza
Experimental: Intravenous (IV) Zanamivir 600mg Twice Daily
600mg of IV zanamivir infusion twice daily plus oral oseltamivir placebo twice daily
Drug: 600mg intravenous (IV) zanamivir and oral oseltamivir placebo
600mg IV zanamivir and oral oseltamivir placebo
Other Name: Relenza
Active Comparator: Oral Oseltamivir 75mg Twice Daily
75mg oral oseltamivir twice daily plus intravenous placebo zanamivir twice daily
Drug: 75mg oral oseltamivir and intravenous zanamivir placebo
75mg oral oseltamivir and IV zanamivir placebo
Other Name: Tamiflu

Detailed Description:

The recent influenza pandemic has highlighted the need for alternative formulations for anti-influenza therapies. This will be an international Phase III, double-blind, double-dummy, 3-arm study to evaluate the efficacy, antiviral activity and safety of IV zanamivir 300 mg or 600 mg twice daily compared to oral oseltamivir 75 mg twice daily for 5 days in hospitalized subjects with laboratory confirmed or suspected influenza infection. For a given subject, the initial 5-day treatment course may be extended for up to 5 additional days if clinical symptoms or patient characteristics as assessed by the investigator warrant further treatment. Alternatively, if the investigator considers that a subject is failing to improve clinically on their randomized treatment, the investigator can choose to initiate the switch/rescue option (600 mg IV zanamivir twice daily) on any day from Day 6 through Day 10 for up to an additional 5 days of treatment. On switching treatments, subjects complete a maximum of 14 days of treatment and are followed-up to Post-Treatment +28 Days.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female aged 16 years; 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 use protocol specified methods of birth control while on study.
  • Vital signs criteria defined as 3 or more of the following at Baseline:

    1. Presence of fever [oral temperature of 38°C or equivalent] at Baseline. However, this requirement is waived if the subject has a history of fever within in the 24 hours prior to Baseline; or, if the subject reported symptoms of feverishness at some time during the 48 hours prior to Baseline.

      AND at least 2 out of the following 4:

    2. Oxygen saturation <95% on room air by trans-cutaneous method or need for any supplemental oxygenation or ventilatory support, or increase in oxygen supplementation requirement of ≥2 litres for subjects with chronic oxygen dependency. For those subjects with a history of chronic hypoxia (without supplemental oxygen), an oxygen saturation of at least 3% below the patient's historical baseline oxygen saturation will satisfy this criterion.
    3. Respiration rate >24 breaths per minute. For those subjects who require ventilatory support or oxygen supplementation, this requirement is waived.
    4. Heart rate >100 beats per minute.
    5. Systolic blood pressure <90 mmHg.
  • Onset of influenza symptoms within 6 days prior to study enrolment. Symptoms may include cough, dyspnea, sore throat, feverishness, myalgias, headache, nasal symptoms (rhinorrhea, congestion), fatigue, diarrhea, anorexia, nausea and vomiting.
  • Clinical symptoms of influenza with positive influenza diagnostic test result or strong suspicion of influenza illness based on clinical symptoms and local surveillance information.
  • Subjects willing and able to give written informed consent to participate in the study and to adhere to the procedures stated in the protocol, or legally acceptable representative willing and able to give written informed consent on behalf of the subject for minors, unconscious adults and those incapable of consenting themselves due to their medical condition, or included as permitted by local regulatory authorities, IRB/IECs or local laws.
  • Severity of any medical illness that, in the Investigator's judgement, justifies hospitalization of the subject for treatment and supportive care
  • 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

Exclusion Criteria:

  • Subjects who have taken more than a total of 3 days (6 doses) of approved anti-influenza therapy (i.e. oral oseltamivir, oral inhaled zanamivir, oral amantadine, oral rimantadine, or oral ribavirin) in the period from onset of symptoms and prior to enrolment.
  • Subjects who, in the opinion of the investigator, are not likely to survive beyond 48 hours from Baseline.
  • Subjects who are considered to require concurrent therapy with another influenza antiviral medication.
  • Subjects who are known or suspected to be hypersensitive to any component of the study medications.
  • Subjects with creatinine clearance ≤10 mL/min who are not being treated with continuous renal replacement therapy (CRRT).
  • Subjects who require Extra Corporeal Membrane Oxygenation (ECMO) at Baseline
  • Subjects who require routine/intermittent hemodialysis or continuous peritoneal dialysis (due to inability to provide appropriate dosing schedule for oseltamivir) at Baseline. CRRT modalities are allowed.
  • Liver toxicity criteria based on local laboratory results obtained within 24 hours of Baseline:

    1. ALT or AST 3xULN and bilirubin 2xULN
    2. ALT 5xULN
  • Underlying chronic liver disease with evidence of severe liver impairment.
  • History of severe 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.
  • Females who are pregnant or are breastfeeding.
  • Treatment with investigational parenteral anti-influenza drugs (IV peramivir, IV zanamivir or IV oseltamivir) in the 4 weeks prior to Baseline.
  • French and Korean subjects: the French or Korean subject has participated in any study using an investigational drug during the previous 30 days.
  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: NCT01231620

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

  Show 167 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01231620     History of Changes
Other Study ID Numbers: 114373
Study First Received: October 28, 2010
Last Updated: March 27, 2014
Health Authority: Brazil: CONEP - National Committee for Research Ethics
New Zealand: Medsafe
Slovakia: State Institute for Drug Control
Colombia: INVIMA
Czech Republic: Státní ústav pro kontrolu léčiv, Oddělení klinického hodnocení
Spain: Agencia Española del Medicamento y Productos Sanitarios
Mexico: Secretaría de Salud
Taiwan: Food and Drug Administration, Department of Health, Executive Yuan
Hungary: National Institute of Pharmacy
Poland: Centralna Ewidencja Badań Klinicznych Urząd Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów Biobójczych
Belgium: Federal Agency for Medicines and Health Products, FAMHP
China: Food and Drug Administration
United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Netherlands: Centrale Commissie Mensgesbonden Onderzoek (Central Committee on Research Involving Human Subjects) Den Haag (The Hague), The Netherlands
Norway: Norwegian Medicines Agency
Russia: Russian Ministry of Health
South Korea: Korea Food and Drug Administration (KFDA)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Hong Kong: Department of Health
South Africa: Medicines Control Council
India: Ministry of Health
Canada: Health Canada
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
Denmark: Danish Medicines Agency
France: Agence Française de Sécurité Sanitaire des Produits de Santé
Thailand: Ministry of Public Health
India: Drugs Controller General of India (DCGI)
Australia: Therapeutic Goods Administration
Greece: National Drug Organisation

Keywords provided by GlaxoSmithKline:
Seasonal Influenza
Relenza
Pandemic
Orthomyxoviridae Infections
Influenza
Influenza A Virus, H1N1 Subtype
Enzyme Inhibitors
Influenza, seasonal
Respiratory Tract Diseases
Zanamivir
Respiratory Tract Infections
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
H1N1
Neuraminidase inhibitor
RNA Virus Infections
Influenza B virus

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

ClinicalTrials.gov processed this record on July 23, 2014