Trial Outcomes & Findings for A Study of Intravenous Oseltamivir [Tamiflu] in Infants With Influenza (NCT NCT01053663)

NCT ID: NCT01053663

Last Updated: 2016-07-27

Results Overview

• Recruitment status: TERMINATED
• Study phase: PHASE1
• Target enrollment: 9 participants
• Primary outcome timeframe: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1
• Results posted on: 2016-07-27

Participant Flow

A total of 2428 participants were prescreened; of which, 2419 failed the prescreening evaluation. The most common reasons for failing the prescreening evaluation included the following: negative influenza diagnosis, not meeting the age criterion, ability to tolerate/absorb oral medication, and inability to comply with the study procedures.

Participant milestones

Measure	Oseltamivir - All Participants 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 age. Participants aged 91 to less than (\<) 365 days received 3 milligrams per kilogram (mg/kg); participants aged 31 to 90 days received 2.5 mg/kg; and participants aged 0 to 30 days received 2 mg/kg. 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	9
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Measure	Oseltamivir - All Participants 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 age. Participants aged 91 to less than (\<) 365 days received 3 milligrams per kilogram (mg/kg); participants aged 31 to 90 days received 2.5 mg/kg; and participants aged 0 to 30 days received 2 mg/kg. 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 Death	2
Overall Study Lost to Follow-up	1
Overall Study Poor IV Access	1
Overall Study Transferred to Another Hospital	1
Overall Study Negative Influenza Diagnosis	1

Baseline Characteristics

A Study of Intravenous Oseltamivir [Tamiflu] in Infants With Influenza

Baseline characteristics by cohort

Measure	Oseltamivir: Age 91 to < 365 Days n=7 Participants Participants aged 91 to \<365 days received oseltamivir 3 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 31 to 90 Days n=1 Participants Participants aged 31 to 90 days received oseltamivir 2.5 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 0 to 30 Days n=1 Participants Participants aged 0 to 30 days received oseltamivir 2 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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.	Total n=9 Participants Total of all reporting groups
Age, Continuous	175.0 days STANDARD_DEVIATION 62.0 • n=5 Participants	41.0 days n=7 Participants	23.0 days n=5 Participants	143.2 days STANDARD_DEVIATION 82.9 • n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants

PRIMARY outcome

Timeframe: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1

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: Age 91 to < 365 Days n=3 Participants Participants aged 91 to \<365 days received oseltamivir 3 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 31 to 90 Days Participants aged 31 to 90 days received oseltamivir 2.5 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 0 to 30 Days n=1 Participants Participants aged 0 to 30 days received oseltamivir 2 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: All Participants Participants 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 age. Participants aged 91 to \<365 days received 3 mg/kg; participants aged 31 to 90 days received 2.5 mg/kg; and participants aged 0 to 30 days received 2 mg/kg. 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	777 hour*nanogram/milliliter (h*ng/mL) Geometric Coefficient of Variation 162.8	—	494 hour*nanogram/milliliter (h*ng/mL)	—
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	5200 hour*nanogram/milliliter (h*ng/mL) Geometric Coefficient of Variation 87.8	—	7510 hour*nanogram/milliliter (h*ng/mL)	—

PRIMARY outcome

Timeframe: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 2

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

Outcome measures

Measure	Oseltamivir: Age 91 to < 365 Days n=3 Participants Participants aged 91 to \<365 days received oseltamivir 3 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 31 to 90 Days n=1 Participants Participants aged 31 to 90 days received oseltamivir 2.5 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 0 to 30 Days Participants aged 0 to 30 days received oseltamivir 2 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: All Participants Participants 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 age. Participants aged 91 to \<365 days received 3 mg/kg; participants aged 31 to 90 days received 2.5 mg/kg; and participants aged 0 to 30 days received 2 mg/kg. 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	988 h*ng/mL Geometric Coefficient of Variation 57.8	481 h*ng/mL	—	—
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 2 Oseltamivir Carboxylate	7270 h*ng/mL Geometric Coefficient of Variation 42.2	5330 h*ng/mL	—	—

PRIMARY outcome

Timeframe: Pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4

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

Outcome measures

Measure	Oseltamivir: Age 91 to < 365 Days n=2 Participants Participants aged 91 to \<365 days received oseltamivir 3 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 31 to 90 Days Participants aged 31 to 90 days received oseltamivir 2.5 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 0 to 30 Days n=1 Participants Participants aged 0 to 30 days received oseltamivir 2 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: All Participants Participants 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 age. Participants aged 91 to \<365 days received 3 mg/kg; participants aged 31 to 90 days received 2.5 mg/kg; and participants aged 0 to 30 days received 2 mg/kg. 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	1520 h*ng/mL Geometric Coefficient of Variation 33.9	—	389 h*ng/mL	—
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 4 Oseltamivir Carboxylate	3880 h*ng/mL Geometric Coefficient of Variation 98.0	—	2070 h*ng/mL	—

PRIMARY outcome

Timeframe: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1

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

Outcome measures

Measure	Oseltamivir: Age 91 to < 365 Days n=3 Participants Participants aged 91 to \<365 days received oseltamivir 3 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 31 to 90 Days Participants aged 31 to 90 days received oseltamivir 2.5 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 0 to 30 Days n=1 Participants Participants aged 0 to 30 days received oseltamivir 2 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: All Participants Participants 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 age. Participants aged 91 to \<365 days received 3 mg/kg; participants aged 31 to 90 days received 2.5 mg/kg; and participants aged 0 to 30 days received 2 mg/kg. 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 on Day 1 Oseltamivir	307 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 315.7	—	203 nanogram/milliliter (ng/mL)	—
Maximum Observed Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate on Day 1 Oseltamivir Carboxylate	736 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 55.5	—	871 nanogram/milliliter (ng/mL)	—

PRIMARY outcome

Timeframe: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 2

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

Outcome measures

Measure	Oseltamivir: Age 91 to < 365 Days n=3 Participants Participants aged 91 to \<365 days received oseltamivir 3 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 31 to 90 Days n=1 Participants Participants aged 31 to 90 days received oseltamivir 2.5 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 0 to 30 Days Participants aged 0 to 30 days received oseltamivir 2 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: All Participants Participants 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 age. Participants aged 91 to \<365 days received 3 mg/kg; participants aged 31 to 90 days received 2.5 mg/kg; and participants aged 0 to 30 days received 2 mg/kg. 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 on Day 2 Oseltamivir	419 ng/mL Geometric Coefficient of Variation 78.4	194 ng/mL	—	—
Cmax of Oseltamivir and Oseltamivir Carboxylate on Day 2 Oseltamivir Carboxylate	1080 ng/mL Geometric Coefficient of Variation 43.6	1050 ng/mL	—	—

PRIMARY outcome

Timeframe: Pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4

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

Outcome measures

Measure	Oseltamivir: Age 91 to < 365 Days n=2 Participants Participants aged 91 to \<365 days received oseltamivir 3 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 31 to 90 Days Participants aged 31 to 90 days received oseltamivir 2.5 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 0 to 30 Days n=1 Participants Participants aged 0 to 30 days received oseltamivir 2 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: All Participants Participants 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 age. Participants aged 91 to \<365 days received 3 mg/kg; participants aged 31 to 90 days received 2.5 mg/kg; and participants aged 0 to 30 days received 2 mg/kg. 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 on Day 4 Oseltamivir	742 ng/mL Geometric Coefficient of Variation 31.1	—	189 ng/mL	—
Cmax of Oseltamivir and Oseltamivir Carboxylate on Day 4 Oseltamivir Carboxylate	1370 ng/mL Geometric Coefficient of Variation 89.6	—	727 ng/mL	—

SECONDARY outcome

Timeframe: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1 and Day 2, pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4

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: Age 91 to < 365 Days n=3 Participants Participants aged 91 to \<365 days received oseltamivir 3 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 31 to 90 Days n=1 Participants Participants aged 31 to 90 days received oseltamivir 2.5 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 0 to 30 Days n=1 Participants Participants aged 0 to 30 days received oseltamivir 2 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: All Participants Participants 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 age. Participants aged 91 to \<365 days received 3 mg/kg; participants aged 31 to 90 days received 2.5 mg/kg; and participants aged 0 to 30 days received 2 mg/kg. 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 1: Oseltamivir (n = 3, 0, 1)	2.51 hours Geometric Coefficient of Variation 55.4	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	2.00 hours	—
Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate Day 1: Oseltamivir Carboxylate (n = 3, 0, 1)	4.57 hours Geometric Coefficient of Variation 32.5	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	5.58 hours	—
Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate Day 2: Oseltamivir (n = 3, 1, 0)	2.02 hours Geometric Coefficient of Variation 1.4	2.13 hours	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 Carboxylate (n = 3, 1, 0)	3.40 hours Geometric Coefficient of Variation 47.8	4.30 hours	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 = 2, 0, 1)	2.02 hours Geometric Coefficient of Variation 1.2	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	1.93 hours	—
Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate Day 4: Oseltamivir Carboxylate (n = 2, 0, 1)	3.85 hours Geometric Coefficient of Variation 6.7	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	3.98 hours	—

SECONDARY outcome

Timeframe: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1 and Day 2, pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4

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: Age 91 to < 365 Days n=3 Participants Participants aged 91 to \<365 days received oseltamivir 3 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 31 to 90 Days n=1 Participants Participants aged 31 to 90 days received oseltamivir 2.5 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 0 to 30 Days n=1 Participants Participants aged 0 to 30 days received oseltamivir 2 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: All Participants Participants 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 age. Participants aged 91 to \<365 days received 3 mg/kg; participants aged 31 to 90 days received 2.5 mg/kg; and participants aged 0 to 30 days received 2 mg/kg. 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 1: Oseltamivir (n = 3, 0, 1)	5.58 ng/mL Geometric Coefficient of Variation 183.0	NA ng/mL Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	2.76 ng/mL	—
Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate Day 1: Oseltamivir Carboxylate (n = 3, 0, 1)	505 ng/mL Geometric Coefficient of Variation 82.9	NA ng/mL Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	503 ng/mL	—
Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate Day 2: Oseltamivir (n = 3, 1, 0)	8.22 ng/mL Geometric Coefficient of Variation 183.5	6.84 ng/mL	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 = 3, 1, 0)	849 ng/mL Geometric Coefficient of Variation 67.9	948 ng/mL	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 = 2, 0, 1)	66.2 ng/mL Geometric Coefficient of Variation 28.8	NA ng/mL Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	10.7 ng/mL	—
Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate Day 4: Oseltamivir Carboxylate (n = 2, 0, 1)	1370 ng/mL Geometric Coefficient of Variation 89.6	NA ng/mL Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	727 ng/mL	—

SECONDARY outcome

Timeframe: Pre-dose (Hour 0), 2, 3-4, 5-7, and 10-12 hours post-dose on Day 1 and Day 2, pre-dose (Hour 0), 2 and 4 hours post-dose on Day 4

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: Age 91 to < 365 Days n=3 Participants Participants aged 91 to \<365 days received oseltamivir 3 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 31 to 90 Days n=1 Participants Participants aged 31 to 90 days received oseltamivir 2.5 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 0 to 30 Days n=1 Participants Participants aged 0 to 30 days received oseltamivir 2 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: All Participants Participants 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 age. Participants aged 91 to \<365 days received 3 mg/kg; participants aged 31 to 90 days received 2.5 mg/kg; and participants aged 0 to 30 days received 2 mg/kg. 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 = 3, 0, 1)	9.62 hours Geometric Coefficient of Variation 24.7	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	10.58 hours	—
Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate Day 1: Oseltamivir Carboxylate (n = 3, 0, 1)	9.62 hours Geometric Coefficient of Variation 24.7	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	10.58 hours	—
Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate Day 2: Oseltamivir (n = 3, 1, 0)	8.55 hours Geometric Coefficient of Variation 51.1	6.47 hours	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 Carboxylate (n = 3, 1, 0)	8.55 hours Geometric Coefficient of Variation 51.1	6.47 hours	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 = 2, 0, 1)	3.85 hours Geometric Coefficient of Variation 6.7	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	3.98 hours	—
Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate Day 4: Oseltamivir Carboxylate (n = 2, 0, 1)	3.85 hours Geometric Coefficient of Variation 6.7	NA hours Geometric Coefficient of Variation NA Data not available as no participant was evaluable.	3.98 hours	—

SECONDARY outcome

Timeframe: Baseline, Days 1, 3, 4, 6, 15

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 or ≥5 times change in the NAI IC50 Visit value from the Baseline value.

Outcome measures

Measure	Oseltamivir: Age 91 to < 365 Days n=4 Participants Participants aged 91 to \<365 days received oseltamivir 3 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 31 to 90 Days Participants aged 31 to 90 days received oseltamivir 2.5 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 0 to 30 Days n=1 Participants Participants aged 0 to 30 days received oseltamivir 2 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: All Participants n=5 Participants Participants 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 age. Participants aged 91 to \<365 days received 3 mg/kg; participants aged 31 to 90 days received 2.5 mg/kg; and participants aged 0 to 30 days received 2 mg/kg. 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.
Number of Participants With Greater Than or Equal to (≥) 5-Fold Change in Neuraminidase Inhibition (NAI) Assay 50 Percent (%) Inhibitory Concentration (IC50) Values Day 1 (n=4, 0, 1, 5)	1 participants	—	0 participants	1 participants
Number of Participants With Greater Than or Equal to (≥) 5-Fold Change in Neuraminidase Inhibition (NAI) Assay 50 Percent (%) Inhibitory Concentration (IC50) Values Day 3 (n=0, 0, 1, 1)	NA participants Data not available as no participant was evaluable in this arm for specified time-point.	—	0 participants	0 participants
Number of Participants With Greater Than or Equal to (≥) 5-Fold Change in Neuraminidase Inhibition (NAI) Assay 50 Percent (%) Inhibitory Concentration (IC50) Values Day 4 (n=3, 0, 0, 3)	1 participants	—	NA participants Data not available as no participant was evaluable in this arm for specified time-point.	1 participants
Number of Participants With Greater Than or Equal to (≥) 5-Fold Change in Neuraminidase Inhibition (NAI) Assay 50 Percent (%) Inhibitory Concentration (IC50) Values Day 6 (n=0, 0, 1, 1)	NA participants Data not available as no participant was evaluable in this arm for specified time-point.	—	0 participants	0 participants
Number of Participants With Greater Than or Equal to (≥) 5-Fold Change in Neuraminidase Inhibition (NAI) Assay 50 Percent (%) Inhibitory Concentration (IC50) Values Day 15 (n=1, 0, 0, 1)	0 participants	—	NA participants Data not available as no participant was evaluable in this arm for specified time-point.	0 participants

SECONDARY outcome

Timeframe: Up to Day 30

Population: Safety population.

Resistance was assessed by neuraminidase (NA) and hemagglutinin (HA) genes sequencing analysis, using Reverse Transcription Polymerase Chain Reaction (RT-PCR).

Outcome measures

Measure	Oseltamivir: Age 91 to < 365 Days n=7 Participants Participants aged 91 to \<365 days received oseltamivir 3 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 31 to 90 Days n=1 Participants Participants aged 31 to 90 days received oseltamivir 2.5 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 0 to 30 Days n=1 Participants Participants aged 0 to 30 days received oseltamivir 2 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: All Participants n=9 Participants Participants 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 age. Participants aged 91 to \<365 days received 3 mg/kg; participants aged 31 to 90 days received 2.5 mg/kg; and participants aged 0 to 30 days received 2 mg/kg. 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.
Number of Participants With Oseltamivir Resistance Mutation	1 participants	0 participants	0 participants	1 participants

Adverse Events

Oseltamivir: Age 31 to 90 Days

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Oseltamivir: Age 91 to < 365 Days

Serious events: 5 serious events

Other events: 4 other events

Deaths: 0 deaths

Oseltamivir: Age 0 to 30 Days

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Oseltamivir: All Participants

Serious events: 5 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Oseltamivir: Age 31 to 90 Days n=1 participants at risk Participants aged 31 to 90 days received oseltamivir 2.5 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 91 to < 365 Days n=7 participants at risk Participants aged 91 to \<365 days received oseltamivir 3 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 0 to 30 Days n=1 participants at risk Participants aged 0 to 30 days received oseltamivir 2 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: All Participants n=9 participants at risk Participants 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 age. Participants aged 91 to \<365 days received 3 mg/kg; participants aged 31 to 90 days received 2.5 mg/kg; and participants aged 0 to 30 days received 2 mg/kg. 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.
General disorders Multi-Organ Failure	0.00% 0/1 • Up to Day 30	14.3% 1/7 • Up to Day 30	0.00% 0/1 • Up to Day 30	11.1% 1/9 • Up to Day 30
Nervous system disorders Cerebral Ischaemia	0.00% 0/1 • Up to Day 30	14.3% 1/7 • Up to Day 30	0.00% 0/1 • Up to Day 30	11.1% 1/9 • Up to Day 30
Respiratory, thoracic and mediastinal disorders Respiratory Disorder	0.00% 0/1 • Up to Day 30	14.3% 1/7 • Up to Day 30	0.00% 0/1 • Up to Day 30	11.1% 1/9 • Up to Day 30
Respiratory, thoracic and mediastinal disorders Respiratory Distress	0.00% 0/1 • Up to Day 30	14.3% 1/7 • Up to Day 30	0.00% 0/1 • Up to Day 30	11.1% 1/9 • Up to Day 30
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/1 • Up to Day 30	14.3% 1/7 • Up to Day 30	0.00% 0/1 • Up to Day 30	11.1% 1/9 • Up to Day 30

Other adverse events

Measure	Oseltamivir: Age 31 to 90 Days n=1 participants at risk Participants aged 31 to 90 days received oseltamivir 2.5 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 91 to < 365 Days n=7 participants at risk Participants aged 91 to \<365 days received oseltamivir 3 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: Age 0 to 30 Days n=1 participants at risk Participants aged 0 to 30 days received oseltamivir 2 mg/kg twice daily (every 12 hours) IV over 5 or 6 days for a total of 10 doses. 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: All Participants n=9 participants at risk Participants 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 age. Participants aged 91 to \<365 days received 3 mg/kg; participants aged 31 to 90 days received 2.5 mg/kg; and participants aged 0 to 30 days received 2 mg/kg. 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.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/1 • Up to Day 30	14.3% 1/7 • Up to Day 30	0.00% 0/1 • Up to Day 30	11.1% 1/9 • Up to Day 30
Cardiac disorders Sinus Bradycardia	0.00% 0/1 • Up to Day 30	14.3% 1/7 • Up to Day 30	0.00% 0/1 • Up to Day 30	11.1% 1/9 • Up to Day 30
Gastrointestinal disorders Abdominal Distension	0.00% 0/1 • Up to Day 30	14.3% 1/7 • Up to Day 30	0.00% 0/1 • Up to Day 30	11.1% 1/9 • Up to Day 30
Gastrointestinal disorders Vomiting	0.00% 0/1 • Up to Day 30	0.00% 0/7 • Up to Day 30	100.0% 1/1 • Up to Day 30	11.1% 1/9 • Up to Day 30
General disorders Application Site Vesicles	0.00% 0/1 • Up to Day 30	0.00% 0/7 • Up to Day 30	100.0% 1/1 • Up to Day 30	11.1% 1/9 • Up to Day 30
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/1 • Up to Day 30	0.00% 0/7 • Up to Day 30	100.0% 1/1 • Up to Day 30	11.1% 1/9 • Up to Day 30
Nervous system disorders Brain Oedema	0.00% 0/1 • Up to Day 30	14.3% 1/7 • Up to Day 30	0.00% 0/1 • Up to Day 30	11.1% 1/9 • Up to Day 30
Renal and urinary disorders Proteinuria	0.00% 0/1 • Up to Day 30	14.3% 1/7 • Up to Day 30	0.00% 0/1 • Up to Day 30	11.1% 1/9 • Up to Day 30
Respiratory, thoracic and mediastinal disorders Pulmonary Hypertension	0.00% 0/1 • Up to Day 30	14.3% 1/7 • Up to Day 30	0.00% 0/1 • Up to Day 30	11.1% 1/9 • Up to Day 30
Skin and subcutaneous tissue disorders Rash	0.00% 0/1 • Up to Day 30	14.3% 1/7 • Up to Day 30	0.00% 0/1 • Up to Day 30	11.1% 1/9 • Up to Day 30
Vascular disorders Haemorrhage	0.00% 0/1 • Up to Day 30	0.00% 0/7 • Up to Day 30	100.0% 1/1 • Up to Day 30	11.1% 1/9 • Up to Day 30
Vascular disorders Hypotension	0.00% 0/1 • Up to Day 30	14.3% 1/7 • Up to Day 30	0.00% 0/1 • Up to Day 30	11.1% 1/9 • Up to Day 30

Additional Information

Medical Communications

Hoffman-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