Trial Outcomes & Findings for A Study of Intravenously Administered Tamiflu (Oseltamivir) in Patients Over 13 Years of Age With Influenza (NCT NCT01050257)

Last Updated: 2013-11-01

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

118 participants

Primary outcome timeframe

Up to 30 days

Results posted on

2013-11-01

Participant Flow

This study included a 5 day treatment period and an optional extension. Participants were considered to have completed treatment if they completed the 5-day course of treatment (IV and/or oral).

Participant milestones

Participant milestones
Measure	Oseltamivir (TAMIFLU®) 100 mg 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 (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 Open Label 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.
Overall Study STARTED	50	53	15
Overall Study Received Treatment	49	50	14
Overall Study Safety Population: Actual Dose Received	48	51	14
Overall Study Intent-to-treat Infected Confirmed	30	32	10
Overall Study Switched to Oral Treatment	28	31	3
Overall Study COMPLETED	39	40	8
Overall Study NOT COMPLETED	11	13	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Oseltamivir (TAMIFLU®) 100 mg 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 (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 Open Label 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.
Overall Study Adverse Event	4	4	2
Overall Study Admin/Other (did not switch to oral)	6	2	2
Overall Study Withdrawal by Subject	0	3	0
Overall Study No reason specified	0	0	2
Overall Study Refused treatment/ Did not Cooperate	1	1	0
Overall Study Violation criteria	0	1	0
Overall Study Failure to return	0	2	0
Overall Study Death	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Oseltamivir (TAMIFLU®) 100 mg n=50 Participants 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 n=53 Participants 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 Open Label n=15 Participants 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.	Total n=118 Participants Total of all reporting groups
Age Continuous	44.8 years STANDARD_DEVIATION 16.68 • n=5 Participants	44.3 years STANDARD_DEVIATION 18.09 • n=7 Participants	66.9 years STANDARD_DEVIATION 18.28 • n=5 Participants	47.4 years STANDARD_DEVIATION 18.93 • n=4 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	27 Participants n=7 Participants	8 Participants n=5 Participants	60 Participants n=4 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	26 Participants n=7 Participants	7 Participants n=5 Participants	58 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 30 days

Population: Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.

Outcome measures

Outcome measures
Measure	Oseltamivir (TAMIFLU®) 100 mg n=48 Participants 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 n=51 Participants 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 Open Label n=14 Participants 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.
Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death AEs on treatment: IV dose	24 Partipants	27 Partipants	11 Partipants
Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death AEs on treatment: Oral dose	10 Partipants	9 Partipants	4 Partipants
Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death AEs off treatment	13 Partipants	13 Partipants	5 Partipants
Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death SAEs on treatment: IV dose	3 Partipants	4 Partipants	2 Partipants
Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death SAEs on treatment: Oral dose	2 Partipants	0 Partipants	2 Partipants
Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death SAEs off treatment	5 Partipants	1 Partipants	3 Partipants
Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death AEs leading to withdrawal on treatment: IV dosing	3 Partipants	3 Partipants	2 Partipants
Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death AEs leading to withdrawal on treatment: Oral dose	1 Partipants	1 Partipants	1 Partipants
Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death AEs leading to withdrawal off treatment	0 Partipants	0 Partipants	0 Partipants
Number of Participants With Adverse Events (AEs), Serious Adverse Events(SAEs, AEs Leading to Withdrawal, and Death Death	1 Partipants	1 Partipants	3 Partipants

SECONDARY outcome

Timeframe: Days 1, 3

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 1, 4, 6, 11, 15 and 30

Population: Intent-to-Treat Infected population included all treated participants who had confirmed influenza infection by culture or RT-PCR.

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).

Outcome measures

Outcome measures
Measure	Oseltamivir (TAMIFLU®) 100 mg n=30 Participants 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 n=32 Participants 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 Open Label n=10 Participants 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.
Percentage of Participants With Viral Shedding by Culture or RT-PCR Day 1 (n=29, 30, 10)	90 Percentage of participants	97 Percentage of participants	90 Percentage of participants
Percentage of Participants With Viral Shedding by Culture or RT-PCR Day 4 (n=28, 28, 10)	64 Percentage of participants	75 Percentage of participants	60 Percentage of participants
Percentage of Participants With Viral Shedding by Culture or RT-PCR Day 6 (n=22, 28, 8)	41 Percentage of participants	36 Percentage of participants	63 Percentage of participants
Percentage of Participants With Viral Shedding by Culture or RT-PCR Day 11 (n=22, 26, 8)	9 Percentage of participants	15 Percentage of participants	13 Percentage of participants
Percentage of Participants With Viral Shedding by Culture or RT-PCR Day 15 (n=17, 24, 7)	0 Percentage of participants	8 Percentage of participants	14 Percentage of participants
Percentage of Participants With Viral Shedding by Culture or RT-PCR Day 30 (n=22, 28, 6)	5 Percentage of participants	4 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Days 1, 4, 6, 11, 15, 30

Population: Intent-to-Treat Infected population included all treated participants who had confirmed influenza infection by culture or RT-PCR.

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.

Outcome measures

Outcome measures
Measure	Oseltamivir (TAMIFLU®) 100 mg n=30 Participants 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 n=32 Participants 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 Open Label n=10 Participants 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.
Percentage of Participants With Viral Shedding by Culture Day 1 (n=29, 30, 10)	76 Percentage of participants	80 Percentage of participants	90 Percentage of participants
Percentage of Participants With Viral Shedding by Culture Day 4 (n=28, 28, 10)	14 Percentage of participants	29 Percentage of participants	30 Percentage of participants
Percentage of Participants With Viral Shedding by Culture Day 6 (n=22, 28, 8)	5 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With Viral Shedding by Culture Day 11 (n=22, 26, 8)	0 Percentage of participants	4 Percentage of participants	0 Percentage of participants
Percentage of Participants With Viral Shedding by Culture Day 15 (n=17, 24, 7)	0 Percentage of participants	4 Percentage of participants	14 Percentage of participants
Percentage of Participants With Viral Shedding by Culture Day 30 (n=22, 28, 6)	5 Percentage of participants	4 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Days 1, 4, 6, 11, 15 and 30

Population: Intent-to-Treat Infected population included all treated participants who had confirmed influenza infection by culture or RT-PCR.

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).

Outcome measures

Outcome measures
Measure	Oseltamivir (TAMIFLU®) 100 mg n=30 Participants 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 n=32 Participants 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 Open Label n=10 Participants 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.
Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) Day 15 (n=17, 24, 7)	0 Percentage of participants	4 Percentage of participants	0 Percentage of participants
Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) Day 1 (n=29, 30, 10)	86 Percentage of participants	93 Percentage of participants	90 Percentage of participants
Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) Day 4 (n=28, 28, 10)	64 Percentage of participants	71 Percentage of participants	60 Percentage of participants
Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) Day 6 (n=22, 28, 8)	41 Percentage of participants	36 Percentage of participants	63 Percentage of participants
Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) Day 11 (n=22, 26, 8)	9 Percentage of participants	12 Percentage of participants	13 Percentage of participants
Percentage of Participants With Viral Shedding by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) Day 30 (n=22, 28, 6)	5 Percentage of participants	4 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 4

Population: Participants from the Intent-to-treat Influenza Infected population with data available for analysis. Only participants with positive influenza results are included.

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).

Outcome measures

Outcome measures
Measure	Oseltamivir (TAMIFLU®) 100 mg n=4 Participants 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 n=8 Participants 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 Open Label n=3 Participants 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.
Change From Baseline in Influenza Titer by Culture at Day 4	-1.38 log10 TCID50 Standard Deviation 1.920	-2.19 log10 TCID50 Standard Deviation 1.186	-3.00 log10 TCID50 Standard Deviation 0.750

SECONDARY outcome

Timeframe: Baseline, Day 4

Population: Participants from the Intent-to-Treat Infected population with data available for analysis. Only participants with positive influenza results are included.

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).

Outcome measures

Outcome measures
Measure	Oseltamivir (TAMIFLU®) 100 mg n=30 Participants 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 n=32 Participants 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 Open Label n=10 Participants 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.
Change From Baseline in Influenza Titer by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at Day 4 Flu A (n=14, 14, 5)	-1.04 log 10 copies/mL Standard Deviation 1.412	-1.30 log 10 copies/mL Standard Deviation 0.883	-1.53 log 10 copies/mL Standard Deviation 0.930
Change From Baseline in Influenza Titer by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) at Day 4 Flu B (n=3, 5, 1)	-0.70 log 10 copies/mL Standard Deviation 1.459	-1.51 log 10 copies/mL Standard Deviation 0.262	-2.27 log 10 copies/mL Standard Deviation NA Unable to calculate standard deviation, data available for only 1 patient.

SECONDARY outcome

Timeframe: Baseline and Hours 12, 24, 36, 48, 60, 72, 84, 96 and 108

Population: Intent-to-Treat Infected population included all treated participants who had confirmed influenza infection by culture or RT-PCR.

Fever was defined as a temperature of ≥ 37.8 C (degrees Celcius).

Outcome measures

Outcome measures
Measure	Oseltamivir (TAMIFLU®) 100 mg n=30 Participants 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 n=32 Participants 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 Open Label n=10 Participants 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.
Percentage of Participants Who Had a Fever During the Study Baseline	23 Percentage of participants	19 Percentage of participants	20 Percentage of participants
Percentage of Participants Who Had a Fever During the Study Hour 12	7 Percentage of participants	9 Percentage of participants	10 Percentage of participants
Percentage of Participants Who Had a Fever During the Study Hour 24	7 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Percentage of Participants Who Had a Fever During the Study Hour 36	3 Percentage of participants	3 Percentage of participants	20 Percentage of participants
Percentage of Participants Who Had a Fever During the Study Hour 48	3 Percentage of participants	6 Percentage of participants	0 Percentage of participants
Percentage of Participants Who Had a Fever During the Study Hour 60	0 Percentage of participants	6 Percentage of participants	0 Percentage of participants
Percentage of Participants Who Had a Fever During the Study Hour 72	0 Percentage of participants	3 Percentage of participants	0 Percentage of participants
Percentage of Participants Who Had a Fever During the Study Hour 96	0 Percentage of participants	3 Percentage of participants	0 Percentage of participants
Percentage of Participants Who Had a Fever During the Study Hour 108	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Percentage of Participants Who Had a Fever During the Study Hour 84	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Up to 30 Days

Population: Participants from the Intent-to-Treat Infected population, all treated participants with confirmed influenza infection by culture or RT-PCR, who had a fever at Baseline.

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.

Outcome measures

Outcome measures
Measure	Oseltamivir (TAMIFLU®) 100 mg n=7 Participants 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 n=6 Participants 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 Open Label n=2 Participants 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.
Time to Resolution of Fever for Participants Who Had a Fever at Baseline	11.8 Hours Interval 7.8 to 43.5	18.6 Hours Interval 8.4 to 66.8	47.7 Hours Data available for only 1 patient (1 patient was censored).

SECONDARY outcome

Timeframe: 30 days

Population: Intent-to-Treat Infected population included all treated participants who had confirmed influenza infection by culture or RT-PCR.

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.

Outcome measures

Outcome measures
Measure	Oseltamivir (TAMIFLU®) 100 mg n=30 Participants 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 n=32 Participants 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 Open Label n=10 Participants 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.
Number of Participants With Viral Resistance	1 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Days 1, 11, 15, 30

Population: Intent-to-Treat population included all treated participants.

Influenza (flu) symptoms were nasal congestion, sore throat, cough, aches and pains, fatigue, headache or chills.

Outcome measures

Outcome measures
Measure	Oseltamivir (TAMIFLU®) 100 mg n=49 Participants 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 n=50 Participants 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 Open Label n=14 Participants 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.
Percentage of Participants With Influenza Symptoms Day 1	100 Percentage of participants	100 Percentage of participants	93 Percentage of participants
Percentage of Participants With Influenza Symptoms Day 11	63 Percentage of participants	64 Percentage of participants	79 Percentage of participants
Percentage of Participants With Influenza Symptoms Day 15	51 Percentage of participants	44 Percentage of participants	64 Percentage of participants
Percentage of Participants With Influenza Symptoms Day 30	33 Percentage of participants	26 Percentage of participants	64 Percentage of participants

Adverse Events

Oseltamivir (TAMIFLU®) 100 mg

Serious events: 9 serious events

Other events: 17 other events

Deaths: 0 deaths

Oseltamivir (TAMIFLU®) 200 mg

Serious events: 5 serious events

Other events: 18 other events

Deaths: 0 deaths

Oseltamivir Open Label

Serious events: 7 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffman-LaRoche

Phone: 800-821-8590

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Oseltamivir (TAMIFLU®) 100 mg n=48 participants at risk 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 n=51 participants at risk 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 Open Label n=14 participants at risk 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.
Renal and urinary disorders Renal failure acute	2.1% 1/48 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/51 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/14 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.
Vascular disorders Deep vein thrombosis	2.1% 1/48 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/51 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/14 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.
Infections and infestations Sepsis	2.1% 1/48 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/51 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	7.1% 1/14 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.1% 1/48 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/51 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/14 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.
Nervous system disorders Cerebrovascular accident	2.1% 1/48 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/51 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/14 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.
Infections and infestations Parainfluenzae virus infection	2.1% 1/48 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/51 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/14 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.
Cardiac disorders Atrial fibrillation	2.1% 1/48 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/51 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/14 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.
Pregnancy, puerperium and perinatal conditions Abortion threatened	2.1% 1/48 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/51 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/14 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.
Cardiac disorders Sinus bradycardia	4.2% 2/48 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/51 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/14 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/48 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	2.0% 1/51 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	7.1% 1/14 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.
General disorders Pyrexia	0.00% 0/48 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	2.0% 1/51 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/14 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.
Blood and lymphatic system disorders Neutropenia	0.00% 0/48 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	2.0% 1/51 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/14 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.
Infections and infestations Lung infection pseudomonal	0.00% 0/48 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	2.0% 1/51 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/14 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.
Gastrointestinal disorders Diarrhoea	0.00% 0/48 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	2.0% 1/51 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/14 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/48 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/51 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	7.1% 1/14 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.
Cardiac disorders Ventricular fibrillation	0.00% 0/48 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/51 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	7.1% 1/14 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.
Cardiac disorders Cardiac arrest	0.00% 0/48 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/51 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	7.1% 1/14 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.
Vascular disorders Hypotension	0.00% 0/48 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/51 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	7.1% 1/14 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.
Injury, poisoning and procedural complications Fall	0.00% 0/48 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/51 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	7.1% 1/14 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.
Renal and urinary disorders Renal failure	0.00% 0/48 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	2.0% 1/51 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.	0.00% 0/14 Safety population included all participants who received treatment and had at least one post-treatment safety assessment. One patient in the 100 mg group actually received 200 mg and is included in the 200 mg group for safety.