Long Term Influenza Prophylaxis With Inhaled Zanamivir or Oral Oseltamivir

NCT00980109 | Completed Phase 4 DMC

• 2 other identifiers: SEA 004N01AO50042
• Study Type: interventional
• Target: 390
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Influenza

Keywords

Influenza Prophylaxis; Long Term; Oral Oseltamivir; Inhaled Zanamivir

Outcome Measures

Primary Outcomes (1)

• 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

  1 year

Secondary Outcomes (1)

• Proportion of subjects who withdraw from the study because of SAEs unlikely or not related to study drug/placebo

  1 year

Study Arms (4)

placebo oseltamivir

PLACEBO COMPARATOR

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

Drug: placebo capsule

zanamivir for inhalation

ACTIVE COMPARATOR

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

placebo inhalation

PLACEBO COMPARATOR

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

active oseltamivir

ACTIVE COMPARATOR

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

Interventions

active oseltamivir DRUG

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.

Also known as: Tamiflu

active oseltamivir

placebo capsule DRUG

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

placebo oseltamivir

zanamivir for inhalation DRUG

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.

Also known as: Rotadisk/Diskhaler

zanamivir for inhalation

placebo for inhalation DRUG

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.

placebo inhalation

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male or female aged 20 - 65 years. Healthy determined by the Investigator based on medical history and screening examinations.
• Read and understand study related materials intended for subject.
• Signed informed consent prior to study participation.
• Willingness and ability to comply with the study protocol for the duration of the trial.
• 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).
• For male subject, he must agree to use an acceptable method of birth control (e.g. abstinence or condom) throughout the study (D120+2).

You may not qualify if:

• Females who are pregnant, trying to get pregnant or are lactating.
• Current or a history of asthma or chronic obstructive pulmonary disease within the last 5 years.
• 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)
• Any other chronic or acute diseases requiring treatment.
• An abnormal ECG indicating disease that requires immediate investigation or treatment
• An abnormal chest x-ray indicating an active disease process.
• A creatinine clearance \< 30 mL/min as determined by Cockcroft-Gault equation (see below)
• AST or ALT ≥ 1.5 x ULN
• Use of a live attenuated influenza vaccine or any anti-influenza drug within 14 days prior to the first dose of study drugs/placebos.
• History of alcohol or substance abuse or dependence which in the opinion of the investigator would interfere with subject compliance or safety
• 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.
• The subject has participated in a clinical trial and has received investigational drugs within 60 days prior to the first dose of study drug.
• Subjects who, in the opinion of the investigator, are unlikely to comply fully with study procedures.
• History of any mental illness requiring hospitalisation or outpatient psychiatric treatment within the last 12 months
• Any suicidal attempt within the previous 5 years.

Sponsors & Collaborators

• University of Oxford: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (2)

Faculty of Medicine Siriraj Hospital

Bangkok, Bangkoknoi, 10700, Thailand

Location

Hospital for Tropical Diseases

Bangkok, 10400, Thailand

Location

MeSH Terms

Conditions

Influenza, Human

Interventions

Oseltamivir; Zanamivir; Inhalation

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Guanidines; Amidines; Sialic Acids; Neuraminic Acids; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Amino Sugars; Carbohydrates; Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 17, 2009
• First Posted: September 18, 2009
• Study Start: September 1, 2009
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: September 22, 2010

Record last verified: 2010-09

Locations

TH (2)