A Study of Tamiflu (Oseltamivir) for Treatment of Influenza With a Focus on (H1N1) 2009 Flu Strain - Full Text View

Purpose

This randomized, double-blind, multi-center study of Tamiflu (Oseltamivir) will evaluate the efficacy against viral activity, the effectiveness in resolving the disease symptoms, and the safety and tolerability in patients with influenza. Patients with (H1N1) 2009 influenza strain or influenza A are eligible for this study. Patients will be randomized to one of four treatment regimens. Patients will receive oral doses of either 75 mg (adults) or 150 mg (adults) of study drug twice daily for 5 or 10 consecutive days. The dose will be body weight-adjusted for pediatric patients.

Condition	Intervention	Phase
Influenza	Drug: Oseltamivir Drug: Placebo	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Randomized, Multicenter Trial of Oseltamivir [Tamiflu] Doses of 75 mg for 5 or 10 Days Versus 150 mg for 5 or 10 Days to Evaluate the Effect on the Duration of Viral Shedding in Influenza Patients With Pandemic (H1N1) 2009

Resource links provided by NLM:

MedlinePlus related topics: Flu

Drug Information available for: Oseltamivir Oseltamivir phosphate

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

Time to Cessation of Viral Shedding [ Time Frame: Day 1 to Day 40 ] [ Designated as safety issue: No ]
The time to cessation of viral shedding was measured by viral culture and defined as the time from treatment initiation to the time of the first negative culture with no subsequent positive cultures. Any patient with a positive culture at the last sample time was censored at that time point. Median time to cessation was estimated from the Kaplan-Meier curve.

Secondary Outcome Measures:

Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture [ Time Frame: Baseline and Days 3, 6, 8, 11, 15 and 40 ] [ Designated as safety issue: No ]
Viral shedding was measured by viral culture from samples obtained from nasal and throat swabs and performed by the central laboratory.
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction [ Time Frame: Baseline and Days 3, 6, 8, 11, 15 and 40 ] [ Designated as safety issue: No ]
Viral shedding was measured by reverse transcriptase polymerase chain reaction (RT-PCR) from samples obtained from nasal and throat swabs and performed by the central laboratory.
Change From Baseline in Influenza Titer Measured by Viral Culture [ Time Frame: Baseline, Days 2 through 15 ] [ Designated as safety issue: No ]
Influenza virus titer measured by viral culture and expressed on a Log10 scale of the 50% Tissue Culture Infective Dose (TCID50; amount of virus required to kill 50% of inoculated tissue culture cells).
Number of Participants With Development of Oseltamivir-Resistant Influenza Virus [ Time Frame: 40 days ] [ Designated as safety issue: No ]
The last positive viral isolate from each patient was tested for reduced sensitivity to oseltamivir. Phenotypic assay was performed to determine the susceptibility of the last positive viral isolate from each patient. If required, a genotypic assay to determine the contribution of both the neuraminidase (NA) and hemagglutinin (HA) genes to decreased susceptibility was also performed.
Time to Resolution of Fever [ Time Frame: Day 1 through Day 40 ] [ Designated as safety issue: No ]
Temperature was recorded by the patient in a diary twice daily for 10 days and once daily thereafter. Fever was defined as a body temperature greater than or including 37.8 degrees Celsius (or ≥ 100.04 Fahrenheit). Time to resolution of fever was defined as the total number of hours from the first dose of study medication to the first time at which temperature is ≤ 37.2 degrees Celsius and lasts at least 21.5 hours. Patients who were still febrile at the end of the study period were censored at that time.
Time to Alleviation of All Clinical Symptoms - Children [ Time Frame: Day 1 to Day 40 ] [ Designated as safety issue: No ]
Daily influenza-like symptoms (such as poor appetite, irritability, low energy, nasal congestion, runny nose etc) were recorded in a diary on a scale from 0 (no problem) to 3 (major problem). A patient is considered free of all clinical influenza symptoms if all symptoms were checked as 'no problem' or 'minor problem' (i.e., symptom score ≤1). Time to alleviation of all clinical symptoms was defined as the number of hours from the first dose to the first time the patient had alleviation of all symptoms. Patients without alleviation of symptoms were censored at the last available assessment.
Time to Alleviation of All Clinical Symptoms - Adults [ Time Frame: Day 1 to Day 40 ] [ Designated as safety issue: No ]
Daily influenza-like symptoms (such as nasal congestion, sore throat, cough, aches and pains, fatigue, headache, chills) were recorded in a diary on a scale from 0 (absent) to 3 (severe). A patient is considered free of all clinical influenza symptoms if all symptoms were checked as 'absent' or 'mild' (i.e., symptom score ≤1). Time to alleviation of all clinical symptoms was defined as the number of hours from the first dose to the first time the patient had alleviation of all symptoms. Patients without alleviation of symptoms were censored at the last available assessment.
Number of Participants Who Developed Secondary Illnesses During the Study [ Time Frame: Day 1 through Day 40 ] [ Designated as safety issue: No ]
The number of participants who developed secondary illnesses due to influenza, including four pre-defined adverse events: otitis media, bronchitis, pneumonia, or sinusitis at any time during the study.
Number of Participants Who Developed Secondary Illnesses That Were Treated With Antibiotics [ Time Frame: Day 1 through Day 40 ] [ Designated as safety issue: No ]
The number of participants who developed secondary illnesses due to influenza, including otitis media, bronchitis, pneumonia, or sinusitis at any time during the study which were treated with antibiotics.

Enrollment:	102
Study Start Date:	November 2009
Study Completion Date:	October 2010
Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Oseltamivir standard dose 5 days Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Drug: Oseltamivir Oseltamivir capsules for participants ≥ 13 years. Other Name: Tamiflu Drug: Oseltamivir Pediatric suspension for participants aged ≤ 12 years. Other Name: Tamiflu Drug: Placebo Matching placebo provided as capsules and as a suspension.
Experimental: Oseltamivir standard dose 10 days Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 10 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 10 days.	Drug: Oseltamivir Oseltamivir capsules for participants ≥ 13 years. Other Name: Tamiflu Drug: Oseltamivir Pediatric suspension for participants aged ≤ 12 years. Other Name: Tamiflu Drug: Placebo Matching placebo provided as capsules and as a suspension.
Experimental: Oseltamivir high dose 5 days Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Drug: Oseltamivir Oseltamivir capsules for participants ≥ 13 years. Other Name: Tamiflu Drug: Oseltamivir Pediatric suspension for participants aged ≤ 12 years. Other Name: Tamiflu Drug: Placebo Matching placebo provided as capsules and as a suspension.
Experimental: Oseltamivir high dose 10 days Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 10 days. Children aged 1- 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 10 days.	Drug: Oseltamivir Oseltamivir capsules for participants ≥ 13 years. Other Name: Tamiflu Drug: Oseltamivir Pediatric suspension for participants aged ≤ 12 years. Other Name: Tamiflu Drug: Placebo Matching placebo provided as capsules and as a suspension.

Eligibility

Ages Eligible for Study:	1 Year and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Pediatric, adolescent and adult patients >/=1 year of age
Fever >/=37.8 degrees C or at least one respiratory symptom (cough, coryza, sore throat, or rhinitis)
Positive rapid diagnostic test for pandemic (H1N1) 2009 virus or influenza A in the 24 hours prior to the first dose of study drug
</=96 hours between onset of influenza-like illness and first dose of oseltamivir

Exclusion Criteria:

Currently receiving any form of renal replacement therapy including hemodialysis, peritoneal dialysis, or hemofiltration
History of chronic renal failure or clinical suspicion of renal failure at baseline
Clinical evidence of hepatic compensation at the time of randomization
Known HIV infection
Vaccination with live attenuated influenza vaccine (LAIV) in the two weeks prior to first dose of study medication

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01032837

Show 100 Study Locations

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director:

Clinical Trials

Hoffmann-La Roche

More Information

No publications provided

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT01032837 History of Changes
Other Study ID Numbers:	NV22155
Study First Received:	December 10, 2009
Results First Received:	July 12, 2012
Last Updated:	September 18, 2012
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Oseltamivir

Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 19, 2013