A Study of Intravenous Tamiflu (Oseltamivir) in Children With Influenza

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01033734
• Collaborator: (none)
• Enrollment: 8
• Locations: 38
• Arm: 1
• Duration (Months): 24
• Patients Per Site: 0.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This open-label study will assess the pharmacokinetics/pharmacodynamics and safety of intravenous (iv) Tamiflu (oseltamivir) in 3 cohorts of children, aged 6-12, 3-5 and 1-2 years, with influenza infection. Patients will receive iv Tamiflu therapy for 5 days (10 doses). For patients whose conditions no longer merit continued iv dosing, therapy may be switched to oral Tamiflu to complete their prescribed course of treatment. If medically necessary, iv or oral therapy with Tamiflu may be continued for up to 5 additional days. Anticipated time on study treatment is 5 to 10 days.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Drug: oseltamivir [Tamiflu]	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Prospective, Pharmacokinetic/Pharmacodynamic and Safety Evaluation of Intravenous Oseltamivir (Tamiflu) in the Treatment of Children 1 to 12 Years of Age With Influenza Infection
• Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single arm	Drug: oseltamivir [Tamiflu]; 5-day course (10 doses), intravenous administration, may be switched to oral administration at the discretion of the investigator; up to 5 additional days of treatment possible.

Outcome Measures

Primary Outcome Measures

1. Area Under the Concentration Versus Time Curve From Time Zero to Last Measurable Plasma Concentration (AUClast) of Oseltamivir and Oseltamivir Carboxylate on Day 1 [Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion.]

2. AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 2 [Day 2: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion]

3. AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 3 [Day 3 (with or after fifth dose): 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion]

4. AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 4 [Day 4: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion]

5. AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 5 [Day 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion]

6. Maximum Observed Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate Day 1 [Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion]

7. Cmax of Oseltamivir and Oseltamivir Carboxylate Day 2 [Day 2: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion]

8. Cmax of Oseltamivir and Oseltamivir Carboxylate Day 3 [Day 3 (with or after fifth dose): 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion]

9. Cmax of Oseltamivir and Oseltamivir Carboxylate Day 4 [Day 4: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion]

10. Cmax of Oseltamivir and Oseltamivir Carboxylate Day 5 [Day 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion]

Secondary Outcome Measures

1. Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate [Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion]

2. Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate [Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion]

3. Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate [Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion]

4. Elimination Rate Constant (ke) of Oseltamivir and Oseltamivir Carboxylate [Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion]

5. Total Clearance of Drug (CL) of Oseltamivir and Oseltamivir Carboxylate [Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion]

6. Volume of Distribution (V) of Oseltamivir and Oseltamivir Carboxylate [Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion]

7. Participants With Greater Than or Equal to (>=) 5-Fold Change in Neuraminidase Inhibition (NAI) Assay 50 Percent (%) Inhibitory Concentration (IC50) Values [Baseline, Day 1, 6 and 30]

   IC50 was defined as the concentration that causes 50% inhibition of viral activity. IC50 values were calculated using NAI assay. The 5-fold change was calculated as either >=5 times change in the NAI IC50 visit value from the Reference value at a visit, >=5 times change in the NAI IC50 Visit value from the Baseline value.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 12 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• children, 1-12 years of age

• diagnosis of influenza

• duration of influenza symptoms </=96 hours prior to first dose of study drug

Exclusion Criteria:

• evidence of severe hepatic decompensation

• patients taking probenecid within 1 week prior to first dose of study drug

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Los Angeles	California	United States	90095
2		Oakland	California	United States	94609-1809
3		Aurora	Colorado	United States	80045
4		Wilmington	Delaware	United States	19803
5		Jacksonville	Florida	United States	32209
6		Chicago	Illinois	United States	60611
7		South Bend	Indiana	United States	46601
8		Wichita	Kansas	United States	67214
9		Louisville	Kentucky	United States	40202
10		Boston	Massachusetts	United States	02111
11		Boston	Massachusetts	United States	02115
12		Boston	Massachusetts	United States	02118
13		Springfield	Massachusetts	United States	01199
14		Detroit	Michigan	United States	48201
15		Duluth	Minnesota	United States	55805
16		Omaha	Nebraska	United States	68131
17		Morristown	New Jersey	United States	07960
18		Bronx	New York	United States	10461
19		Brooklyn	New York	United States	11203
20		New York	New York	United States	10016
21		Stony Brook	New York	United States	11794-8161
22		Syracuse	New York	United States	13210
23		Durham	North Carolina	United States	27705
24		Raleigh	North Carolina	United States	27610
25		Akron	Ohio	United States	44308
26		Cleveland	Ohio	United States	44106
27		Dayton	Ohio	United States	45404
28		Toledo	Ohio	United States	43606
29		Toledo	Ohio	United States	43608
30		Oklahoma City	Oklahoma	United States	73104
31		Tyrone	Pennsylvania	United States	16686
32		Providence	Rhode Island	United States	02903
33		Charleston	South Carolina	United States	29524
34		Houston	Texas	United States	77030
35		Richmond	Virginia	United States	23298
36		Madison	Wisconsin	United States	53792
37		Petach Tikva		Israel	19202
38		Beirut		Lebanon	11-236

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01033734
• Other Study ID Numbers: NP25139
• First Posted: Dec 16, 2009
• Last Update Posted: Aug 24, 2016
• Last Verified: Jul 1, 2016

• Additional relevant MeSH terms: Influenza, Human; Oseltamivir

Study Results

Participant Flow

Pre-assignment Detail	A total of 2836 participants were prescreened, of which, 2828 failed evaluation. The most common reasons for screen failure included: negative influenza diagnosis, not meeting the age criterion, ability to tolerate/absorb oral medication, and an inability to comply with the study procedures.

Arm/Group Title	Oseltamivir: Overall
Arm/Group Description	Participants received oseltamivir (Tamiflu) twice daily (every 12 hours) intravenously (IV) over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to (≤) 23 kilogram (kg) received 3 milligrams per kilogram (mg/kg); participants with body weight more than (>) 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight >40 kg received 100 milligrams (mg). For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
Period Title: Overall Study
STARTED	8
COMPLETED	7
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Oseltamivir: Overall
Arm/Group Description	Participants received oseltamivir (Tamiflu) twice daily IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight ≤23 kg received 3 mg/kg; participants with body weight ˃23 kg to 40 kg received 2.5 mg/kg; and participants with body weight ˃40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
Overall Participants	8
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	4.8 (3.1)
Sex: Female, Male (Count of Participants)
Female	2 25%
Male	6 75%

Outcome Measures

1. Primary Outcome

Title	Area Under the Concentration Versus Time Curve From Time Zero to Last Measurable Plasma Concentration (AUClast) of Oseltamivir and Oseltamivir Carboxylate on Day 1
Time Frame	Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion.

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) population included all treated participants who had at least one blood sample evaluable for drug concentration level. Number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	Oseltamivir: 6 to 12 Years	Oseltamivir: 3 to 5 Years	Oseltamivir: 1 to 2 Years
Arm/Group Description	Participants aged 6 to 12 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 3 to 5 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 1 to 2 Years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
Measure Participants	1	3	0
Oseltamivir	829	1460 (46.3)
Oseltamivir Carboxylate	1700	4550 (61.1)

2. Primary Outcome

Title	AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 2
Time Frame	Day 2: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

Outcome Measure Data

Analysis Population Description

PK population. Number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	Oseltamivir: 6 to 12 Years	Oseltamivir: 3 to 5 Years	Oseltamivir: 1 to 2 Years
Arm/Group Description	Participants aged 6 to 12 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 3 to 5 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 1 to 2 Years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
Measure Participants	0	1	1
Oseltamivir	1070	1920
Oseltamivir Carboxylate	5970	6760

3. Primary Outcome

Title	AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 3
Time Frame	Day 3 (with or after fifth dose): 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

Outcome Measure Data

Analysis Population Description

PK population. Number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	Oseltamivir: 6 to 12 Years	Oseltamivir: 3 to 5 Years	Oseltamivir: 1 to 2 Years
Arm/Group Description	Participants aged 6 to 12 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 3 to 5 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 1 to 2 Years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
Measure Participants	1	0	0
Oseltamivir	943
Oseltamivir Carboxylate	2000

4. Primary Outcome

Title	AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 4
Time Frame	Day 4: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

Outcome Measure Data

Analysis Population Description

PK population. Number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	Oseltamivir: 6 to 12 Years	Oseltamivir: 3 to 5 Years	Oseltamivir: 1 to 2 Years
Arm/Group Description	Participants aged 6 to 12 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 3 to 5 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 1 to 2 Years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
Measure Participants	0	1	0
Oseltamivir	2480
Oseltamivir Carboxylate	3800

5. Primary Outcome

Title	AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 5
Time Frame	Day 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

Outcome Measure Data

Analysis Population Description

PK population. Number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	Oseltamivir: 6 to 12 Years	Oseltamivir: 3 to 5 Years	Oseltamivir: 1 to 2 Years
Arm/Group Description	Participants aged 6 to 12 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 3 to 5 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 1 to 2 Years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
Measure Participants	1	0	0
Oseltamivir	1010
Oseltamivir Carboxylate	2820

6. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate Day 1
Time Frame	Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion

Outcome Measure Data

Analysis Population Description

PK population. Number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	Oseltamivir: 6 to 12 Years	Oseltamivir: 3 to 5 Years	Oseltamivir: 1 to 2 Years
Arm/Group Description	Participants aged 6 to 12 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 3 to 5 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 1 to 2 Years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
Measure Participants	1	3	0
Oseltamivir	360	753 (36.9)
Oseltamivir Carboxylate	311	499 (55.1)

7. Primary Outcome

Title	Cmax of Oseltamivir and Oseltamivir Carboxylate Day 2
Time Frame	Day 2: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

Outcome Measure Data

Analysis Population Description

PK population. Number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	Oseltamivir: 6 to 12 Years	Oseltamivir: 3 to 5 Years	Oseltamivir: 1 to 2 Years
Arm/Group Description	Participants aged 6 to 12 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 3 to 5 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 1 to 2 Years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
Measure Participants	0	1	1
Oseltamivir	500	1270
Oseltamivir Carboxylate	663	725

8. Primary Outcome

Title	Cmax of Oseltamivir and Oseltamivir Carboxylate Day 3
Time Frame	Day 3 (with or after fifth dose): 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

Outcome Measure Data

Analysis Population Description

PK population. Number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	Oseltamivir: 6 to 12 Years	Oseltamivir: 3 to 5 Years	Oseltamivir: 1 to 2 Years
Arm/Group Description	Participants aged 6 to 12 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 3 to 5 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 1 to 2 Years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
Measure Participants	1	0	0
Oseltamivir	404
Oseltamivir Carboxylate	237

9. Primary Outcome

Title	Cmax of Oseltamivir and Oseltamivir Carboxylate Day 4
Time Frame	Day 4: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

Outcome Measure Data

Analysis Population Description

PK population. Number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	Oseltamivir: 6 to 12 Years	Oseltamivir: 3 to 5 Years	Oseltamivir: 1 to 2 Years
Arm/Group Description	Participants aged 6 to 12 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 3 to 5 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 1 to 2 Years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
Measure Participants	0	1	0
Oseltamivir	915
Oseltamivir Carboxylate	549

10. Primary Outcome

Title	Cmax of Oseltamivir and Oseltamivir Carboxylate Day 5
Time Frame	Day 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

Outcome Measure Data

Analysis Population Description

PK population. Number of participants analyzed = participants who were evaluable for this outcome.

Arm/Group Title	Oseltamivir: 6 to 12 Years	Oseltamivir: 3 to 5 Years	Oseltamivir: 1 to 2 Years
Arm/Group Description	Participants aged 6 to 12 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 3 to 5 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 1 to 2 Years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
Measure Participants	1	0	0
Oseltamivir	403
Oseltamivir Carboxylate	408

11. Secondary Outcome

Title	Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate
Time Frame	Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

Outcome Measure Data

Analysis Population Description

PK population. Number of participants analyzed = participants who were evaluable for this outcome, n = number of participants evaluable for specified categories.

Arm/Group Title	Oseltamivir: 6 to 12 Years	Oseltamivir: 3 to 5 Years	Oseltamivir: 1 to 2 Years
Arm/Group Description	Participants aged 6 to 12 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 3 to 5 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 1 to 2 Years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
Measure Participants	1	3	1
Day 1: Oseltamivir (n = 1, 3, 0)	2.00	1.26 (41.7)	NA (NA)
Day 1: Oseltamivir Carboxylate (n = 1, 3, 0)	4.00	4.61 (53.3)	NA (NA)
Day 2: Oseltamivir (n = 0, 1, 1)	NA (NA)	2.00 (NA)	1.00
Day 2: Oseltamivir Carboxylate (n = 0, 1, 1)	NA (NA)	4.62 (NA)	6.00
Day 3: Oseltamivir (n = 1, 0, 0)	1.05	NA (NA)	NA (NA)
Day 3: Oseltamivir Carboxylate (n = 1, 0, 0)	3.05	NA (NA)	NA (NA)
Day 4: Oseltamivir (n = 0, 1, 0)	NA (NA)	2.50 (NA)	NA (NA)
Day 4: Oseltamivir Carboxylate (n = 0, 1, 0)	NA (NA)	8.05 (NA)	NA (NA)
Day 5: Oseltamivir (n = 1, 0, 0)	2.00	NA (NA)	NA (NA)
Day 5: Oseltamivir Carboxylate (n = 1, 0, 0)	4.08	NA (NA)	NA (NA)

12. Secondary Outcome

Title	Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate
Time Frame	Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

Outcome Measure Data

Analysis Population Description

PK population. Number of participants analyzed = participants who were evaluable for this outcome, n = number of participants evaluable for specified categories.

Arm/Group Title	Oseltamivir: 6 to 12 Years	Oseltamivir: 3 to 5 Years	Oseltamivir: 1 to 2 Years
Arm/Group Description	Participants aged 6 to 12 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 3 to 5 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 1 to 2 Years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
Measure Participants	1	3	1
Day 1: Oseltamivir (n = 1, 3, 0)	4.40	2.41 (80.6)	NA (NA)
Day 1: Oseltamivir Carboxylate (n = 1, 3, 0)	237	308 (74.4)	NA (NA)
Day 2: Oseltamivir (n = 0, 2, 1)	NA (NA)	25.2 (1704911.2)	4.76
Day 2: Oseltamivir Carboxylate (n = 0, 2, 1)	NA (NA)	319 (0.44)	484
Day 3: Oseltamivir (n = 1, 0, 0)	2.60	NA (NA)	NA (NA)
Day 3: Oseltamivir Carboxylate (n = 1, 0, 0)	149	NA (NA)	NA (NA)
Day 4: Oseltamivir (n = 0, 1, 0)	NA (NA)	25.1 (NA)	NA (NA)
Day 4: Oseltamivir Carboxylate (n = 0, 1, 0)	NA (NA)	549 (NA)	NA (NA)
Day 5: Oseltamivir (n = 1, 0, 0)	15.1	NA (NA)	NA (NA)
Day 5: Oseltamivir Carboxylate (n = 1, 0, 0)	339	NA (NA)	NA (NA)

13. Secondary Outcome

Title	Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate
Time Frame	Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

Outcome Measure Data

Analysis Population Description

PK population. Number of participants analyzed = participants who were evaluable for this outcome, n = number of participants evaluable for specified categories.

Arm/Group Title	Oseltamivir: 6 to 12 Years	Oseltamivir: 3 to 5 Years	Oseltamivir: 1 to 2 Years
Arm/Group Description	Participants aged 6 to 12 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 3 to 5 years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 1 to 2 Years received oseltamivir twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight less than or equal to 23 kg received 3 mg/kg; participants with body weight more than 23 kg to 40 kg received 2.5 mg/kg; and participants with body weight more than 40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
Measure Participants	1	3	1
Day 1: Oseltamivir (n = 1, 3, 0)	7.42	10.50 (23.4)	NA (NA)
Day 1: Oseltamivir Carboxylate (n = 1, 3, 0)	7.42	11.98 (0.2)	NA (NA)
Day 2: Oseltamivir (n = 0, 2, 1)	NA (NA)	3.50 (448.5)	12.00
Day 2: Oseltamivir Carboxylate (n = 0, 2, 1)	NA (NA)	3.50 (448.47)	12.00
Day 3: Oseltamivir (n = 1, 0, 0)	10.13	NA (NA)	NA (NA)
Day 3: Oseltamivir Carboxylate (n = 1, 0, 0)	10.13	NA (NA)	NA (NA)
Day 4: Oseltamivir (n = 0, 1, 0)	NA (NA)	8.05 (NA)	NA (NA)
Day 4: Oseltamivir Carboxylate (n = 0, 1, 0)	NA (NA)	8.05 (NA)	NA (NA)
Day 5: Oseltamivir (n = 1, 0, 0)	7.92	NA (NA)	NA (NA)
Day 5: Oseltamivir Carboxylate (n = 1, 0, 0)	7.92	NA (NA)	NA (NA)

14. Secondary Outcome

Title	Elimination Rate Constant (ke) of Oseltamivir and Oseltamivir Carboxylate
Time Frame	Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

Outcome Measure Data

Analysis Population Description

Data not available as no participant was evaluable for specified time-points.

Arm/Group Title	Oseltamivir: Overall
Arm/Group Description	Participants received oseltamivir (Tamiflu) twice daily IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight <= 23 kg received 3 mg/kg; participants with body weight ˃23 kg to 40 kg received 2.5 mg/kg; and participants with body weight ˃40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
Measure Participants	0

15. Secondary Outcome

Title	Total Clearance of Drug (CL) of Oseltamivir and Oseltamivir Carboxylate
Time Frame	Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

Outcome Measure Data

Analysis Population Description

Data not available as no participant was evaluable for specified time-points.

Arm/Group Title	Oseltamivir: Overall
Arm/Group Description	Participants received oseltamivir (Tamiflu) twice daily IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight <= 23 kg received 3 mg/kg; participants with body weight ˃23 kg to 40 kg received 2.5 mg/kg; and participants with body weight ˃40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
Measure Participants	0

16. Secondary Outcome

Title	Volume of Distribution (V) of Oseltamivir and Oseltamivir Carboxylate
Time Frame	Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

Outcome Measure Data

Analysis Population Description

Data not collected because of changes in planned analysis, due to early study termination.

Arm/Group Title	Oseltamivir: Overall
Arm/Group Description	Participants received oseltamivir (Tamiflu) twice daily IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight <= 23 kg received 3 mg/kg; participants with body weight ˃23 kg to 40 kg received 2.5 mg/kg; and participants with body weight ˃40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
Measure Participants	0

17. Secondary Outcome

Title	Participants With Greater Than or Equal to (>=) 5-Fold Change in Neuraminidase Inhibition (NAI) Assay 50 Percent (%) Inhibitory Concentration (IC50) Values
Description	IC50 was defined as the concentration that causes 50% inhibition of viral activity. IC50 values were calculated using NAI assay. The 5-fold change was calculated as either >=5 times change in the NAI IC50 visit value from the Reference value at a visit, >=5 times change in the NAI IC50 Visit value from the Baseline value.
Time Frame	Baseline, Day 1, 6 and 30

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least one dose of IV study medication and had a safety assessment performed after initiation of treatment. Here, number of participants analyzed = participants evaluable for this outcome measure, and n = participants evaluable for specified time-point, for each arm, respectively.

Arm/Group Title	Oseltamivir: Overall	Oseltamivir: 6 to 12 Years	Oseltamivir: 3 to 5 Years	Oseltamivir: 1 to 2 Years
Arm/Group Description	Participants received oseltamivir (Tamiflu) twice daily IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight <= 23 kg received 3 mg/kg; participants with body weight ˃23 kg to 40 kg received 2.5 mg/kg; and participants with body weight ˃40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 6 to 12 years received oseltamivir twice daily IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight <=23 kg received 3 mg/kg; participants with body weight ˃23 kg to 40 kg received 2.5 mg/kg; and participants with body weight >40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 3 to 5 years received oseltamivir twice daily IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight <=23 kg received 3 mg/kg; participants with body weight ˃23 kg to 40 kg received 2.5 mg/kg; and participants with body weight ˃40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.	Participants aged 1 to 2 Years received oseltamivir twice daily IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight <=23 kg received 3 mg/kg; participants with body weight ˃23 kg to 40 kg received 2.5 mg/kg; and participants with body weight ˃40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
Measure Participants	6	2	3	1
Day 1 (n=6, 2, 3, 1)	1 12.5%	0 NaN	1 NaN	0 NaN
Day 6 (n=1, 0, 1, 0)	1 12.5%	NA NaN	1 NaN	NA NaN
Day 30 (n=1, 1, 0, 0)	0 0%	0 NaN	NA NaN	NA NaN

Adverse Events

Time Frame	Up to 30 days
Arm/Group Title	Oseltamivir: Overall		Oseltamivir: 6 to 12 Years		Oseltamivir: 3 to 5 Years		Oseltamivir: 1 to 2 Years
Arm/Group Description	Participants received oseltamivir (Tamiflu) twice daily IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight <= 23 kg received 3 mg/kg; participants with body weight ˃23 kg to 40 kg received 2.5 mg/kg; and participants with body weight ˃40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.		Participants aged 6 to 12 years received oseltamivir twice daily IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight <=23 kg received 3 mg/kg; participants with body weight ˃23 kg to 40 kg received 2.5 mg/kg; and participants with body weight >40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.		Participants aged 3 to 5 years received oseltamivir twice daily IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight <=23 kg received 3 mg/kg; participants with body weight ˃23 kg to 40 kg received 2.5 mg/kg; and participants with body weight ˃40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.		Participants aged 1 to 2 Years received oseltamivir twice daily IV over 5 or 6 days for a total of 10 doses. The oseltamivir doses were based on participant's body weight. Participants with body weight <=23 kg received 3 mg/kg; participants with body weight ˃23 kg to 40 kg received 2.5 mg/kg; and participants with body weight ˃40 kg received 100 mg. For participants who did not receive all 10 doses IV, treatment could be completed with oral oseltamivir suspension (twice daily). If medically necessary, participants were allowed to receive an additional 10 doses of IV or oral oseltamivir after the initial 10 doses.
All Cause Mortality
	Oseltamivir: Overall		Oseltamivir: 6 to 12 Years		Oseltamivir: 3 to 5 Years		Oseltamivir: 1 to 2 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Oseltamivir: Overall		Oseltamivir: 6 to 12 Years		Oseltamivir: 3 to 5 Years		Oseltamivir: 1 to 2 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/8 (25%)		1/2 (50%)		1/5 (20%)		0/1 (0%)
General disorders
Pyrexia	1/8 (12.5%)	1	0/2 (0%)	0	1/5 (20%)	1	0/1 (0%)	0
Infections and infestations
Sepsis	1/8 (12.5%)	1	0/2 (0%)	0	1/5 (20%)	1	0/1 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchospasm	1/8 (12.5%)	1	1/2 (50%)	1	0/5 (0%)	0	0/1 (0%)	0
Other (Not Including Serious) Adverse Events
	Oseltamivir: Overall		Oseltamivir: 6 to 12 Years		Oseltamivir: 3 to 5 Years		Oseltamivir: 1 to 2 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/8 (62.5%)		0/2 (0%)		4/5 (80%)		1/1 (100%)
Cardiac disorders
Left Ventricular Dysfunction	1/8 (12.5%)	1	0/2 (0%)	0	1/5 (20%)	1	0/1 (0%)	0
General disorders
Catheter Site Erosion	1/8 (12.5%)	1	0/2 (0%)	0	1/5 (20%)	1	0/1 (0%)	0
Device Expulsion	1/8 (12.5%)	1	0/2 (0%)	0	1/5 (20%)	1	0/1 (0%)	0
Drug Withdrawal Syndrome	1/8 (12.5%)	1	0/2 (0%)	0	0/5 (0%)	0	1/1 (100%)	1
Infusion Site Erythema	1/8 (12.5%)	1	0/2 (0%)	0	1/5 (20%)	1	0/1 (0%)	0
Investigations
Body Temperature Increased	1/8 (12.5%)	1	0/2 (0%)	0	1/5 (20%)	1	0/1 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	1/8 (12.5%)	1	0/2 (0%)	0	1/5 (20%)	1	0/1 (0%)	0
Rhinorrhoea	1/8 (12.5%)	1	0/2 (0%)	0	1/5 (20%)	1	0/1 (0%)	0
Skin and subcutaneous tissue disorders
Ingrowing Nail	1/8 (12.5%)	1	0/2 (0%)	0	1/5 (20%)	1	0/1 (0%)	0
Pain of Skin	1/8 (12.5%)	1	0/2 (0%)	0	1/5 (20%)	1	0/1 (0%)	0

Limitations/Caveats

Low number of participants enrolled in the study at the time that the study was terminated limits conclusions that can be derived from the study data.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.