A Study of Intravenously Administered Tamiflu (Oseltamivir) in Patients Over 13 Years of Age With Influenza

Phase 3

Completed

• Conditions: Influenza
• Interventions: Drug: Oseltamivir IV; Drug: Oseltamivir Oral

• Registration Number: NCT01050257
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This partially randomized, multi-center parallel-group study will evaluate the safety, pharmacokinetics and the effect on viral load and viral shedding of Tamiflu (Oseltamivir) in patients with influenza. Adult and adolescent patients will be randomized to receive either 100 mg or 200 mg of study drug intravenously every 12 hours. Investigators and patients are blinded to knowledge of the assigned dose of Tamiflu. There is an option to convert to oral Tamiflu after 6 intravenous infusions. The anticipated time on study treatment is 5 days, with an optional treatment extension of a further 5 days, if necessary. There will be a non-randomized, open-label treatment group for patients with moderate/severe renal impairment or renal failure. Intravenous dose levels and frequency will be adjusted appropriately to their renal situation.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-01
• Study First Submitted: 2010-01-14
• Study First Submitted QC: 2010-01-14
• Study First Posted: 2010-01-15
• Primary Completion: 2012-09
• Study Completion: 2012-09
• Status Verified: 2013-08
• Results First Submitted: 2013-08-28
• Results First Submitted QC: 2013-08-28
• Last Update Submitted: 2013-08-28
• Results First Posted: 2013-11-01
• Last Update Posted: 2013-11-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 118

Inclusion Criteria

• Adult and adolescent patients, 13 years of age and older
• Diagnosis of influenza
• ≤ 144 hours between the onset of influenza-like illness and first dose of study drug

Non-randomized, open-label treatment group:

• Patients with moderate/severe renal impairment or renal failure with creatinine clearance 10-60 mL/min

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Exclusion Criteria

• Clinical evidence of severe hepatic decompensation at the time of randomization
• Acute ischemia or significant arrhythmia

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oseltamivir Open Label	Oseltamivir Oral	Moderate/Severe renal impaired participants received open label oseltamivir IV or oseltamivir capsules at reduced doses for 5 days as per protocol. If necessary, after completing the 5 days of treatment, participants could receive additional treatment with study drug as per protocol.
Oseltamivir Open Label	Oseltamivir IV	Moderate/Severe renal impaired participants received open label oseltamivir IV or oseltamivir capsules at reduced doses for 5 days as per protocol. If necessary, after completing the 5 days of treatment, participants could receive additional treatment with study drug as per protocol.
Oseltamivir (TAMIFLU®) 100 mg	Oseltamivir IV	Oseltamivir (TAMIFLU®) 100 mg intravenous (IV) infused over 2 hours, two times a day (every 12 hours) for 5 days. At the discretion of the investigator after 3 days of treatment (6 doses), participants could either continue IV treatment or switch to 75 mg oral oseltamivir twice daily to complete the 5 days of treatment. If necessary, after completing the 5 days of treatment, participants could receive additional treatment with study drug (IV or oral) for up to 5 days.
Oseltamivir (TAMIFLU®) 100 mg	Oseltamivir Oral	Oseltamivir (TAMIFLU®) 100 mg intravenous (IV) infused over 2 hours, two times a day (every 12 hours) for 5 days. At the discretion of the investigator after 3 days of treatment (6 doses), participants could either continue IV treatment or switch to 75 mg oral oseltamivir twice daily to complete the 5 days of treatment. If necessary, after completing the 5 days of treatment, participants could receive additional treatment with study drug (IV or oral) for up to 5 days.
Oseltamivir (TAMIFLU®) 200 mg	Oseltamivir IV	Oseltamivir (TAMIFLU®) 200 mg intravenous (IV) infused over 2 hours, two times a day (every 12 hours) for 5 days. At the discretion of the investigator after 3 days of treatment (6 doses), participants could either continue IV treatment or switch to 150 mg oral oseltamivir twice daily for 5 days. If necessary, after completing the 5 days of treatment, participants could receive additional treatment with study drug (IV or oral) for up to 5 days.
Oseltamivir (TAMIFLU®) 200 mg	Oseltamivir Oral	Oseltamivir (TAMIFLU®) 200 mg intravenous (IV) infused over 2 hours, two times a day (every 12 hours) for 5 days. At the discretion of the investigator after 3 days of treatment (6 doses), participants could either continue IV treatment or switch to 150 mg oral oseltamivir twice daily for 5 days. If necessary, after completing the 5 days of treatment, participants could receive additional treatment with study drug (IV or oral) for up to 5 days.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death	Up to 30 days	Safety was assessed by adverse events (AEs) as measured by the collection of AEs, vital signs, electrocardiograms and laboratory parameters. An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.; On treatment = AEs that started between the day of first dose and within 2 days after the last dose. Off treatment = AEs that started more than 2 days after the last dose of study drug.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics	Days 1, 3
Percentage of Participants With Viral Shedding by Culture or RT-PCR	Days 1, 4, 6, 11, 15 and 30	Nasal and throat swabs were collected on Days 1, 4, 6, 11, 15, and 30 and were sent to a central laboratory for analysis. The presence of viral shedding was determined by a positive culture \[log10 median tissue culture infective dose (TCID50) \> 0.5) or detection by RT-PCR (log 10 copies/mL).
Percentage of Participants With Viral Shedding by Culture	Days 1, 4, 6, 11, 15, 30	Nasal and throat swabs were collected on Days 1, 4, 6, 11, 15, and 30 and were sent to a central laboratory for analysis. The presence of viral shedding was determined by a positive culture=log10 median tissue culture infective dose (TCID50) \> 0.5.
Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)	Days 1, 4, 6, 11, 15 and 30	Nasal and throat swabs were collected on Days 1, 4, 6, 11, 15, and 30 and were sent to a central laboratory for analysis. The presence of viral shedding was determined by detection by RT-PCR (log 10 copies/mL).
Change From Baseline in Influenza Titer by Culture at Day 4	Baseline, Day 4	Nasal and throat swabs collected at Baseline and Day 4 were sent to a laboratory for analysis. Viral influenza titer (amount of virus present) was determined by culture. A log 10 median tissue culture infective dose (TCID50) \> 0.5= Positive culture. A negative change from Baseline indicated improvement (less virus present).
Change From Baseline in Influenza Titer by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at Day 4	Baseline, Day 4	Nasal and throat swabs were collected at Baseline and Day 4 and were sent to a central laboratory for analysis. Influenza Viral titers (amount of virus present) were determined by RT-PCR for Flu A and Flu B and were reported in log 10 copies/milliliter (mL). A negative change from Baseline indicated improvement (less virus present).
Percentage of Participants Who Had a Fever During the Study	Baseline and Hours 12, 24, 36, 48, 60, 72, 84, 96 and 108	Fever was defined as a temperature of ≥ 37.8 C (degrees Celcius).
Time to Resolution of Fever for Participants Who Had a Fever at Baseline	Baseline, Up to 30 Days	Fever was defined as a temperature of ≥ 37.8 C (degrees Celsius). Resolution of fever was a temperature ≤ 37.2 for at least 21.5 hours.
Number of Participants With Viral Resistance	30 days	Nasal and Throat swabs were collected on Days 1, 4, 6, 11, 15 and 30 and were sent to a central laboratory for testing. Viral resistance was determined by phenotypic and genotypic testing.
Percentage of Participants With Influenza Symptoms	Days 1, 11, 15, 30	Influenza (flu) symptoms were nasal congestion, sore throat, cough, aches and pains, fatigue, headache or chills.