Trial Outcomes & Findings for A Study of Intravenous Tamiflu (Oseltamivir) in Children With Influenza (NCT NCT01033734)

NCT ID: NCT01033734

Last Updated: 2016-08-24

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 8 participants
• Primary outcome timeframe: Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion.
• Results posted on: 2016-08-24

Participant Flow

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.

Participant milestones

Measure	Oseltamivir: Overall 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.
Overall Study STARTED	8
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure

Oseltamivir: Overall 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.

Overall Study Withdrawal by Subject

1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Oseltamivir: Overall n=8 Participants 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.
Age, Continuous	4.8 years STANDARD_DEVIATION 3.1 • n=93 Participants
Sex: Female, Male Female	2 Participants n=93 Participants
Sex: Female, Male Male	6 Participants n=93 Participants

PRIMARY outcome

Timeframe: Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion.

Population: 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.

Outcome measures

Measure	Oseltamivir: 6 to 12 Years n=1 Participants 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.	Oseltamivir: 3 to 5 Years n=3 Participants 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.	Oseltamivir: 1 to 2 Years 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.	Oseltamivir: 1 to 2 Years 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.
Area Under the Concentration Versus Time Curve From Time Zero to Last Measurable Plasma Concentration (AUClast) of Oseltamivir and Oseltamivir Carboxylate on Day 1 Oseltamivir	829 hour*nanogram/milliliter (h*ng/mL)	1460 hour*nanogram/milliliter (h*ng/mL) Geometric Coefficient of Variation 46.3	—	—
Area Under the Concentration Versus Time Curve From Time Zero to Last Measurable Plasma Concentration (AUClast) of Oseltamivir and Oseltamivir Carboxylate on Day 1 Oseltamivir Carboxylate	1700 hour*nanogram/milliliter (h*ng/mL)	4550 hour*nanogram/milliliter (h*ng/mL) Geometric Coefficient of Variation 61.1	—	—

PRIMARY outcome

Timeframe: Day 2: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

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

Outcome measures

Measure	Oseltamivir: 6 to 12 Years 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.	Oseltamivir: 3 to 5 Years n=1 Participants 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.	Oseltamivir: 1 to 2 Years n=1 Participants 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.	Oseltamivir: 1 to 2 Years 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.
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 2 Oseltamivir	—	1070 h*ng/mL	1920 h*ng/mL	—
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 2 Oseltamivir Carboxylate	—	5970 h*ng/mL	6760 h*ng/mL	—

PRIMARY outcome

Timeframe: Day 3 (with or after fifth dose): 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

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

Outcome measures

Measure	Oseltamivir: 6 to 12 Years n=1 Participants 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.	Oseltamivir: 3 to 5 Years 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.	Oseltamivir: 1 to 2 Years 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.	Oseltamivir: 1 to 2 Years 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.
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 3 Oseltamivir	943 hr*ng/mL	—	—	—
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 3 Oseltamivir Carboxylate	2000 hr*ng/mL	—	—	—

PRIMARY outcome

Timeframe: Day 4: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

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

Outcome measures

Measure	Oseltamivir: 6 to 12 Years 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.	Oseltamivir: 3 to 5 Years n=1 Participants 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.	Oseltamivir: 1 to 2 Years 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.	Oseltamivir: 1 to 2 Years 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.
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 4 Oseltamivir	—	2480 hr*ng/mL	—	—
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 4 Oseltamivir Carboxylate	—	3800 hr*ng/mL	—	—

PRIMARY outcome

Timeframe: Day 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

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

Outcome measures

Measure	Oseltamivir: 6 to 12 Years n=1 Participants 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.	Oseltamivir: 3 to 5 Years 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.	Oseltamivir: 1 to 2 Years 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.	Oseltamivir: 1 to 2 Years 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.
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 5 Oseltamivir	1010 hr*ng/mL	—	—	—
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 5 Oseltamivir Carboxylate	2820 hr*ng/mL	—	—	—

PRIMARY outcome

Timeframe: Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion

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

Outcome measures

Measure	Oseltamivir: 6 to 12 Years n=1 Participants 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.	Oseltamivir: 3 to 5 Years n=3 Participants 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.	Oseltamivir: 1 to 2 Years 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.	Oseltamivir: 1 to 2 Years 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.
Maximum Observed Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate Day 1 Oseltamivir	360 nanograms/milliliter (ng/mL)	753 nanograms/milliliter (ng/mL) Geometric Coefficient of Variation 36.9	—	—
Maximum Observed Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate Day 1 Oseltamivir Carboxylate	311 nanograms/milliliter (ng/mL)	499 nanograms/milliliter (ng/mL) Geometric Coefficient of Variation 55.1	—	—

PRIMARY outcome

Timeframe: Day 2: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

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

Outcome measures

Measure	Oseltamivir: 6 to 12 Years 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.	Oseltamivir: 3 to 5 Years n=1 Participants 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.	Oseltamivir: 1 to 2 Years n=1 Participants 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.	Oseltamivir: 1 to 2 Years 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.
Cmax of Oseltamivir and Oseltamivir Carboxylate Day 2 Oseltamivir	—	500 ng/mL	1270 ng/mL	—
Cmax of Oseltamivir and Oseltamivir Carboxylate Day 2 Oseltamivir Carboxylate	—	663 ng/mL	725 ng/mL	—

PRIMARY outcome

Timeframe: Day 3 (with or after fifth dose): 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

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

Outcome measures

Measure	Oseltamivir: 6 to 12 Years n=1 Participants 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.	Oseltamivir: 3 to 5 Years 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.	Oseltamivir: 1 to 2 Years 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.	Oseltamivir: 1 to 2 Years 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.
Cmax of Oseltamivir and Oseltamivir Carboxylate Day 3 Oseltamivir	404 ng/mL	—	—	—
Cmax of Oseltamivir and Oseltamivir Carboxylate Day 3 Oseltamivir Carboxylate	237 ng/mL	—	—	—

PRIMARY outcome

Timeframe: Day 4: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

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

Outcome measures

Measure	Oseltamivir: 6 to 12 Years 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.	Oseltamivir: 3 to 5 Years n=1 Participants 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.	Oseltamivir: 1 to 2 Years 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.	Oseltamivir: 1 to 2 Years 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.
Cmax of Oseltamivir and Oseltamivir Carboxylate Day 4 Oseltamivir	—	915 ng/mL	—	—
Cmax of Oseltamivir and Oseltamivir Carboxylate Day 4 Oseltamivir Carboxylate	—	549 ng/mL	—	—

PRIMARY outcome

Timeframe: Day 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion

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

Outcome measures

Measure	Oseltamivir: 6 to 12 Years n=1 Participants 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.	Oseltamivir: 3 to 5 Years 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.	Oseltamivir: 1 to 2 Years 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.	Oseltamivir: 1 to 2 Years 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.
Cmax of Oseltamivir and Oseltamivir Carboxylate Day 5 Oseltamivir	403 ng/mL	—	—	—
Cmax of Oseltamivir and Oseltamivir Carboxylate Day 5 Oseltamivir Carboxylate	408 ng/mL	—	—	—

SECONDARY outcome

Timeframe: 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

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

Outcome measures

Measure	Oseltamivir: 6 to 12 Years n=1 Participants 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.	Oseltamivir: 3 to 5 Years n=3 Participants 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.	Oseltamivir: 1 to 2 Years n=1 Participants 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.	Oseltamivir: 1 to 2 Years 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.
Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate Day 2: Oseltamivir Carboxylate (n = 0, 1, 1)	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable	4.62 hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable	6.00 hours	—
Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate Day 1: Oseltamivir (n = 1, 3, 0)	2.00 hours	1.26 hours Geometric Coefficient of Variation 41.7	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable	—
Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate Day 1: Oseltamivir Carboxylate (n = 1, 3, 0)	4.00 hours	4.61 hours Geometric Coefficient of Variation 53.3	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable	—
Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate Day 2: Oseltamivir (n = 0, 1, 1)	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable	2.00 hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable	1.00 hours	—
Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate Day 3: Oseltamivir (n = 1, 0, 0)	1.05 hours	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable	—
Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate Day 3: Oseltamivir Carboxylate (n = 1, 0, 0)	3.05 hours	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable	—
Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate Day 4: Oseltamivir (n = 0, 1, 0)	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable	2.50 hours Geometric Coefficient of Variation NA Standard deviation not applicable as only 1 participant was evaluable	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable	—
Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate Day 4: Oseltamivir Carboxylate (n = 0, 1, 0)	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable	8.05 hours Geometric Coefficient of Variation NA Standard deviation not applicable as only 1 participant was evaluable	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable	—
Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate Day 5: Oseltamivir (n = 1, 0, 0)	2.00 hours	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable	—
Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate Day 5: Oseltamivir Carboxylate (n = 1, 0, 0)	4.08 hours	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable	—

SECONDARY outcome

Timeframe: 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

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

Outcome measures

Measure	Oseltamivir: 6 to 12 Years n=1 Participants 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.	Oseltamivir: 3 to 5 Years n=3 Participants 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.	Oseltamivir: 1 to 2 Years n=1 Participants 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.	Oseltamivir: 1 to 2 Years 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.
Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate Day 2: Oseltamivir (n = 0, 2, 1)	NA ng/mL Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	25.2 ng/mL Geometric Coefficient of Variation 1704911.2	4.76 ng/mL	—
Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate Day 1: Oseltamivir (n = 1, 3, 0)	4.40 ng/mL	2.41 ng/mL Geometric Coefficient of Variation 80.6	NA ng/mL Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	—
Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate Day 1: Oseltamivir Carboxylate (n = 1, 3, 0)	237 ng/mL	308 ng/mL Geometric Coefficient of Variation 74.4	NA ng/mL Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	—
Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate Day 2: Oseltamivir Carboxylate (n = 0, 2, 1)	NA ng/mL Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	319 ng/mL Geometric Coefficient of Variation 0.44	484 ng/mL	—
Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate Day 3: Oseltamivir (n = 1, 0, 0)	2.60 ng/mL	NA ng/mL Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	NA ng/mL Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	—
Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate Day 3: Oseltamivir Carboxylate (n = 1, 0, 0)	149 ng/mL	NA ng/mL Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	NA ng/mL Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	—
Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate Day 4: Oseltamivir (n = 0, 1, 0)	NA ng/mL Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	25.1 ng/mL Geometric Coefficient of Variation NA Standard deviation not applicable as only 1 participant was evaluable.	NA ng/mL Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	—
Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate Day 4: Oseltamivir Carboxylate (n = 0, 1, 0)	NA ng/mL Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	549 ng/mL Geometric Coefficient of Variation NA Standard deviation not applicable as only 1 participant was evaluable.	NA ng/mL Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	—
Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate Day 5: Oseltamivir (n = 1, 0, 0)	15.1 ng/mL	NA ng/mL Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	NA ng/mL Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	—
Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate Day 5: Oseltamivir Carboxylate (n = 1, 0, 0)	339 ng/mL	NA ng/mL Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	NA ng/mL Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	—

SECONDARY outcome

Timeframe: 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

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

Outcome measures

Measure	Oseltamivir: 6 to 12 Years n=1 Participants 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.	Oseltamivir: 3 to 5 Years n=3 Participants 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.	Oseltamivir: 1 to 2 Years n=1 Participants 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.	Oseltamivir: 1 to 2 Years 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.
Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate Day 1: Oseltamivir (n = 1, 3, 0)	7.42 hours	10.50 hours Geometric Coefficient of Variation 23.4	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	—
Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate Day 1: Oseltamivir Carboxylate (n = 1, 3, 0)	7.42 hours	11.98 hours Geometric Coefficient of Variation 0.2	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	—
Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate Day 2: Oseltamivir (n = 0, 2, 1)	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	3.50 hours Geometric Coefficient of Variation 448.5	12.00 hours	—
Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate Day 2: Oseltamivir Carboxylate (n = 0, 2, 1)	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	3.50 hours Geometric Coefficient of Variation 448.47	12.00 hours	—
Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate Day 3: Oseltamivir (n = 1, 0, 0)	10.13 hours	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	—
Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate Day 3: Oseltamivir Carboxylate (n = 1, 0, 0)	10.13 hours	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	—
Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate Day 4: Oseltamivir (n = 0, 1, 0)	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	8.05 hours Geometric Coefficient of Variation NA Standard deviation not applicable as only 1 participant was evaluable.	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	—
Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate Day 4: Oseltamivir Carboxylate (n = 0, 1, 0)	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	8.05 hours Geometric Coefficient of Variation NA Standard deviation not applicable as only 1 participant was evaluable.	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	—
Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate Day 5: Oseltamivir (n = 1, 0, 0)	7.92 hours	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	—
Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate Day 5: Oseltamivir Carboxylate (n = 1, 0, 0)	7.92 hours	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	—

SECONDARY outcome

Timeframe: 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

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Day 1, 6 and 30

Population: 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.

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.

Outcome measures

Measure	Oseltamivir: 6 to 12 Years n=6 Participants 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.	Oseltamivir: 3 to 5 Years n=2 Participants 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.	Oseltamivir: 1 to 2 Years n=3 Participants 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.	Oseltamivir: 1 to 2 Years n=1 Participants 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.
Participants With Greater Than or Equal to (>=) 5-Fold Change in Neuraminidase Inhibition (NAI) Assay 50 Percent (%) Inhibitory Concentration (IC50) Values Day 1 (n=6, 2, 3, 1)	1 Participants	0 Participants	1 Participants	0 Participants
Participants With Greater Than or Equal to (>=) 5-Fold Change in Neuraminidase Inhibition (NAI) Assay 50 Percent (%) Inhibitory Concentration (IC50) Values Day 6 (n=1, 0, 1, 0)	1 Participants	NA Participants Data not available as no participant was evaluable in this arm for specified time-point.	1 Participants	NA Participants Data not available as no participant was evaluable in this arm for specified time-point.
Participants With Greater Than or Equal to (>=) 5-Fold Change in Neuraminidase Inhibition (NAI) Assay 50 Percent (%) Inhibitory Concentration (IC50) Values Day 30 (n=1, 1, 0, 0)	0 Participants	0 Participants	NA Participants Data not available as no participant was evaluable in this arm for specified time-point.	NA Participants Data not available as no participant was evaluable in this arm for specified time-point.

Adverse Events

Oseltamivir: Overall

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Oseltamivir: 6 to 12 Years

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Oseltamivir: 3 to 5 Years

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Oseltamivir: 1 to 2 Years

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Oseltamivir: Overall n=8 participants at risk 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.	Oseltamivir: 6 to 12 Years n=2 participants at risk 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.	Oseltamivir: 3 to 5 Years n=5 participants at risk 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.	Oseltamivir: 1 to 2 Years n=1 participants at risk 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.
Respiratory, thoracic and mediastinal disorders Bronchospasm	12.5% 1/8 • Number of events 1 • Up to 30 days	50.0% 1/2 • Number of events 1 • Up to 30 days	0.00% 0/5 • Up to 30 days	0.00% 0/1 • Up to 30 days
Infections and infestations Sepsis	12.5% 1/8 • Number of events 1 • Up to 30 days	0.00% 0/2 • Up to 30 days	20.0% 1/5 • Number of events 1 • Up to 30 days	0.00% 0/1 • Up to 30 days
General disorders Pyrexia	12.5% 1/8 • Number of events 1 • Up to 30 days	0.00% 0/2 • Up to 30 days	20.0% 1/5 • Number of events 1 • Up to 30 days	0.00% 0/1 • Up to 30 days

Other adverse events

Measure	Oseltamivir: Overall n=8 participants at risk 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.	Oseltamivir: 6 to 12 Years n=2 participants at risk 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.	Oseltamivir: 3 to 5 Years n=5 participants at risk 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.	Oseltamivir: 1 to 2 Years n=1 participants at risk 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.
Cardiac disorders Left Ventricular Dysfunction	12.5% 1/8 • Number of events 1 • Up to 30 days	0.00% 0/2 • Up to 30 days	20.0% 1/5 • Number of events 1 • Up to 30 days	0.00% 0/1 • Up to 30 days
General disorders Catheter Site Erosion	12.5% 1/8 • Number of events 1 • Up to 30 days	0.00% 0/2 • Up to 30 days	20.0% 1/5 • Number of events 1 • Up to 30 days	0.00% 0/1 • Up to 30 days
General disorders Device Expulsion	12.5% 1/8 • Number of events 1 • Up to 30 days	0.00% 0/2 • Up to 30 days	20.0% 1/5 • Number of events 1 • Up to 30 days	0.00% 0/1 • Up to 30 days
General disorders Drug Withdrawal Syndrome	12.5% 1/8 • Number of events 1 • Up to 30 days	0.00% 0/2 • Up to 30 days	0.00% 0/5 • Up to 30 days	100.0% 1/1 • Number of events 1 • Up to 30 days
General disorders Infusion Site Erythema	12.5% 1/8 • Number of events 1 • Up to 30 days	0.00% 0/2 • Up to 30 days	20.0% 1/5 • Number of events 1 • Up to 30 days	0.00% 0/1 • Up to 30 days
Investigations Body Temperature Increased	12.5% 1/8 • Number of events 1 • Up to 30 days	0.00% 0/2 • Up to 30 days	20.0% 1/5 • Number of events 1 • Up to 30 days	0.00% 0/1 • Up to 30 days
Respiratory, thoracic and mediastinal disorders Cough	12.5% 1/8 • Number of events 1 • Up to 30 days	0.00% 0/2 • Up to 30 days	20.0% 1/5 • Number of events 1 • Up to 30 days	0.00% 0/1 • Up to 30 days
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	12.5% 1/8 • Number of events 1 • Up to 30 days	0.00% 0/2 • Up to 30 days	20.0% 1/5 • Number of events 1 • Up to 30 days	0.00% 0/1 • Up to 30 days
Skin and subcutaneous tissue disorders Ingrowing Nail	12.5% 1/8 • Number of events 1 • Up to 30 days	0.00% 0/2 • Up to 30 days	20.0% 1/5 • Number of events 1 • Up to 30 days	0.00% 0/1 • Up to 30 days
Skin and subcutaneous tissue disorders Pain of Skin	12.5% 1/8 • Number of events 1 • Up to 30 days	0.00% 0/2 • Up to 30 days	20.0% 1/5 • Number of events 1 • Up to 30 days	0.00% 0/1 • Up to 30 days

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: genentech@druginfo.com

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