Long Term Influenza Prophylaxis With Inhaled Zanamivir or Oral Oseltamivir (SEA 004)

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
University of Oxford
ClinicalTrials.gov Identifier:
NCT00980109
First received: September 17, 2009
Last updated: September 21, 2010
Last verified: September 2010
  Purpose

This is a multicenter, randomised, four arms placebo controlled study to evaluate the safety and tolerability of 10 mg inhaled zanamivir once a day and 75 mg oseltamivir capsule orally once a day relative to placebo over 16 weeks (112 days). Enrolled subjects will be randomly assigned to 2:1:2:1 ratio (active oseltamivir: placebo: active zanamivir: placebo) on one of the four study treatment groups.

It is hypothesized that oseltamivir and zanamivir will protect participants from becoming infected with influenza.


Condition Intervention Phase
Influenza
Drug: active oseltamivir
Drug: placebo capsule
Drug: zanamivir for inhalation
Drug: placebo for inhalation
Phase 4

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: Prevention
Official Title: A Phase IV, Multi-center, Randomized, Partially Double Blinded, Placebo Controlled Study, to Evaluate the Safety of Daily Inhaled Zanamivir 10 mg Versus Placebo and Daily Oral Oseltamivir 75 mg Versus Placebo for Influenza Prophylaxis in Healthy Volunteers for 16 Weeks

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • Proportion of subjects who withdraw from the study because of serious adverse events (SAEs) that are possibly or probably or definitely related to the study drug [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Proportion of subjects who withdraw from the study because of SAEs unlikely or not related to study drug/placebo [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Enrollment: 390
Study Start Date: September 2009
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo oseltamivir
Placebo capsules, one capsule daily for 112 days. The capsule should be administered at approximately the same time each day.
Drug: placebo capsule
Placebo capsules, one capsule daily for 112 days. The capsule should be administered at approximately the same time each day.
Active Comparator: zanamivir for inhalation
Zanamivir for inhalation, (5 mg per inhalation), two inhalations, once daily using a ROTADISK/DISKHALER for 112 days. The dose should be administered at approximately the same time each day.
Drug: zanamivir for inhalation
Zanamivir for inhalation, (5 mg per inhalation), two inhalations, once daily using a ROTADISK/DISKHALER for 112 days. The dose should be administered at approximately the same time each day.
Other Name: Rotadisk/Diskhaler
Placebo Comparator: placebo inhalation
Placebo (lactose powder), two inhalations, once daily using a ROTADISK/ DISKHALER for 112 days. The dose should be administered at approximately the same time each day.
Drug: placebo for inhalation
Placebo (lactose powder), two inhalations, once daily using a ROTADISK/ DISKHALER for 112 days. The dose should be administered at approximately the same time each day.
Active Comparator: active oseltamivir
Oseltamivir capsules (75 mg per capsule), one capsule daily by mouth (PO) for 112 days. The dose should be administered at approximately the same time each day.
Drug: active oseltamivir
Oseltamivir capsules (75 mg per capsule), one capsule daily by mouth (PO) for 112 days. The dose should be administered at approximately the same time each day.
Other Name: Tamiflu

Detailed Description:

We plan to recruit 130 non-pregnant subjects including Health Care Workers, which refer to anyone who works in the hospital, into each active arm and 65 healthy, non-pregnant subjects including Health Care Workers into each placebo arm for a total of 390 study subjects from 4 study sites in Bangkok and Nonthaburi province, Thailand: (i) Faculty of Medicine Siriraj Hospital, (ii) Bamrasnaradura Infectious Diseases Institute, (iii) Chest Disease Institute, and (iv) Hospital for Tropical Diseases.

Randomisation Groups:

Zanamivir for inhalation, (5 mg per inhalation), two inhalations, once daily using a ROTADISK/DISKHALER for 112 days. The dose should be administered at approximately the same time each day.

Placebo (lactose powder), two inhalations, once daily using a ROTADISK/ DISKHALER for 112 days. The dose should be administered at approximately the same time each day.

Oseltamivir capsules (75 mg per capsule), one capsule daily by mouth (PO) for 112 days. The dose should be administered at approximately the same time each day.

Placebo capsules, one capsule daily for 112 days. The capsule should be administered at approximately the same time each day.

Study duration

The study is expected to last up to about 12 months. The study will consist of:

  • a screening visit
  • 10 study visits: Days 0 , 7 (+2), 14 (+2), 28 (+2), 42 (+2), 56 (+2), 70 (+2), 84 (+2), 98 (+2) and 112 (+2) and
  • One follow-up visit on Day 120 (+2)
  Eligibility

Ages Eligible for Study:   20 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • A subject will be eligible for inclusion in this study only if all of the following criteria apply:

    1. Healthy male or female aged 20 - 65 years. Healthy determined by the Investigator based on medical history and screening examinations.
    2. Read and understand study related materials intended for subject.
    3. Signed informed consent prior to study participation.
    4. Willingness and ability to comply with the study protocol for the duration of the trial.
    5. Female subject who is of reproductive potential agrees to use an acceptable method of birth control (e.g., intrauterine device, abstinence or hormonal contraceptive drug) throughout the study (D120+2).
    6. For male subject, he must agree to use an acceptable method of birth control (e.g. abstinence or condom) throughout the study (D120+2).

      Exclusion Criteria:

  • A subject will not be eligible for inclusion in this study if any of the following apply:

    1. Females who are pregnant, trying to get pregnant or are lactating.
    2. Current or a history of asthma or chronic obstructive pulmonary disease within the last 5 years.
    3. Abnormal pulmonary function test according to The Thoracic Society of Thailand Guidelines for Pulmonary Function Tests: (i) FVC < 80% of the predicted value for age and sex or (ii) FEV1/FVC <70%. (see Appendix 2)
    4. Any other chronic or acute diseases requiring treatment.
    5. An abnormal ECG indicating disease that requires immediate investigation or treatment
    6. An abnormal chest x-ray indicating an active disease process.
    7. A creatinine clearance < 30 mL/min as determined by Cockcroft-Gault equation (see below)
    8. AST or ALT ≥ 1.5 x ULN
    9. Use of a live attenuated influenza vaccine or any anti-influenza drug within 14 days prior to the first dose of study drugs/placebos.
    10. History of alcohol or substance abuse or dependence which in the opinion of the investigator would interfere with subject compliance or safety
    11. Subjects who have a history of allergy to the study drug or drugs of the same class, or a history of severe drug (e.g. toxic epidermal necrolysis) or other allergy (e.g. previous history of anaphylaxis) that, in the opinion of the investigator, contraindicates participation in the trial.
    12. The subject has participated in a clinical trial and has received investigational drugs within 60 days prior to the first dose of study drug.
    13. Subjects who, in the opinion of the investigator, are unlikely to comply fully with study procedures.
    14. History of any mental illness requiring hospitalisation or outpatient psychiatric treatment within the last 12 months
    15. Any suicidal attempt within the previous 5 years.
    16. Screening HADS anxiety or depression score > 8.
    17. Hemoglobin <11g/dL or neutropenia of < 1000 per microlitre or a platelet count of less than 100,000 cells/mm3 Cockroft formula: CrCl (mL/min) = (140 - age) x Wt / 72 x serum creatinine (females x 0.85), age in years, Wt in kg, serum creatinine in mg/dL.
  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: NCT00980109

Locations
Thailand
Faculty of Medicine Siriraj Hospital
Bangkok, Bangkoknoi, Thailand, 10700
Hospital for Tropical Diseases
Bangkok, Thailand, 10400
Sponsors and Collaborators
University of Oxford
  More Information

No publications provided

Responsible Party: The Chancellor, Masters and Scholars of the University of Oxford
ClinicalTrials.gov Identifier: NCT00980109     History of Changes
Other Study ID Numbers: SEA 004, N01-AO-50042
Study First Received: September 17, 2009
Last Updated: September 21, 2010
Health Authority: Thailand: Ministry of Public Health
Thailand: Ethics Committees
Thailand: Food and Drug Administration

Keywords provided by University of Oxford:
Influenza Prophylaxis
Long Term
Oral Oseltamivir
Inhaled Zanamivir

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

ClinicalTrials.gov processed this record on October 01, 2014