Influenza
Conditions
Brief summary
This open-label study will assess the pharmacokinetics/pharmacodynamics and safety of intravenous (iv) Tamiflu (oseltamivir) in 3 cohorts of children, aged 6-12, 3-5 and 1-2 years, with influenza infection. Patients will receive iv Tamiflu therapy for 5 days (10 doses). For patients whose conditions no longer merit continued iv dosing, therapy may be switched to oral Tamiflu to complete their prescribed course of treatment. If medically necessary, iv or oral therapy with Tamiflu may be continued for up to 5 additional days. Anticipated time on study treatment is 5 to 10 days.
Interventions
5-day course (10 doses), intravenous administration, may be switched to oral administration at the discretion of the investigator; up to 5 additional days of treatment possible.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* children, 1-12 years of age * diagnosis of influenza * duration of influenza symptoms \</=96 hours prior to first dose of study drug
Exclusion criteria
* evidence of severe hepatic decompensation * patients taking probenecid within 1 week prior to first dose of study drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Cmax of Oseltamivir and Oseltamivir Carboxylate Day 5 | Day 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion |
| AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 3 | Day 3 (with or after fifth dose): 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion |
| AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 4 | Day 4: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion |
| AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 5 | Day 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion |
| Maximum Observed Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate Day 1 | Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion |
| Cmax of Oseltamivir and Oseltamivir Carboxylate Day 2 | Day 2: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion |
| Cmax of Oseltamivir and Oseltamivir Carboxylate Day 3 | Day 3 (with or after fifth dose): 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion |
| Cmax of Oseltamivir and Oseltamivir Carboxylate Day 4 | Day 4: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion |
| Area Under the Concentration Versus Time Curve From Time Zero to Last Measurable Plasma Concentration (AUClast) of Oseltamivir and Oseltamivir Carboxylate on Day 1 | Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion. |
| AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 2 | Day 2: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion | — |
| Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion | — |
| Elimination Rate Constant (ke) of Oseltamivir and Oseltamivir Carboxylate | Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion | — |
| Total Clearance of Drug (CL) of Oseltamivir and Oseltamivir Carboxylate | Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion | — |
| Volume of Distribution (V) of Oseltamivir and Oseltamivir Carboxylate | Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion | — |
| Participants With Greater Than or Equal to (>=) 5-Fold Change in Neuraminidase Inhibition (NAI) Assay 50 Percent (%) Inhibitory Concentration (IC50) Values | Baseline, Day 1, 6 and 30 | IC50 was defined as the concentration that causes 50% inhibition of viral activity. IC50 values were calculated using NAI assay. The 5-fold change was calculated as either \>=5 times change in the NAI IC50 visit value from the Reference value at a visit, \>=5 times change in the NAI IC50 Visit value from the Baseline value. |
| Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion | — |
Countries
Israel, Lebanon, United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Oseltamivir: Overall 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. | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Oseltamivir: Overall |
|---|---|
| Age, Continuous | 4.8 years STANDARD_DEVIATION 3.1 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 8 | 0 / 2 | 4 / 5 | 1 / 1 |
| serious Total, serious adverse events | 2 / 8 | 1 / 2 | 1 / 5 | 0 / 1 |
Outcome results
Primary
Area Under the Concentration Versus Time Curve From Time Zero to Last Measurable Plasma Concentration (AUClast) of Oseltamivir and Oseltamivir Carboxylate on Day 1
Time frame: Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion.
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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir: 6 to 12 Years | 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) | — |
| Oseltamivir: 6 to 12 Years | 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) | — |
| Oseltamivir: 3 to 5 Years | 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 | 1460 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 46.3 |
| Oseltamivir: 3 to 5 Years | 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 | 4550 hour*nanogram/milliliter (h*ng/mL) | Geometric Coefficient of Variation 61.1 |
Primary
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 2
Time frame: Day 2: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
Population: PK population. Number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Oseltamivir: 3 to 5 Years | AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 2 | Oseltamivir | 1070 h*ng/mL |
| Oseltamivir: 3 to 5 Years | AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 2 | Oseltamivir Carboxylate | 5970 h*ng/mL |
| Oseltamivir: 1 to 2 Years | AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 2 | Oseltamivir | 1920 h*ng/mL |
| Oseltamivir: 1 to 2 Years | AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 2 | Oseltamivir Carboxylate | 6760 h*ng/mL |
Primary
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 3
Time frame: Day 3 (with or after fifth dose): 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
Population: PK population. Number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Oseltamivir: 6 to 12 Years | AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 3 | Oseltamivir Carboxylate | 2000 hr*ng/mL |
| Oseltamivir: 6 to 12 Years | AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 3 | Oseltamivir | 943 hr*ng/mL |
Primary
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 4
Time frame: Day 4: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
Population: PK population. Number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Oseltamivir: 3 to 5 Years | AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 4 | Oseltamivir | 2480 hr*ng/mL |
| Oseltamivir: 3 to 5 Years | AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 4 | Oseltamivir Carboxylate | 3800 hr*ng/mL |
Primary
AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 5
Time frame: Day 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
Population: PK population. Number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Oseltamivir: 6 to 12 Years | AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 5 | Oseltamivir | 1010 hr*ng/mL |
| Oseltamivir: 6 to 12 Years | AUClast of Oseltamivir and Oseltamivir Carboxylate on Day 5 | Oseltamivir Carboxylate | 2820 hr*ng/mL |
Primary
Cmax of Oseltamivir and Oseltamivir Carboxylate Day 2
Time frame: Day 2: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
Population: PK population. Number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Oseltamivir: 3 to 5 Years | Cmax of Oseltamivir and Oseltamivir Carboxylate Day 2 | Oseltamivir | 500 ng/mL |
| Oseltamivir: 3 to 5 Years | Cmax of Oseltamivir and Oseltamivir Carboxylate Day 2 | Oseltamivir Carboxylate | 663 ng/mL |
| Oseltamivir: 1 to 2 Years | Cmax of Oseltamivir and Oseltamivir Carboxylate Day 2 | Oseltamivir | 1270 ng/mL |
| Oseltamivir: 1 to 2 Years | Cmax of Oseltamivir and Oseltamivir Carboxylate Day 2 | Oseltamivir Carboxylate | 725 ng/mL |
Primary
Cmax of Oseltamivir and Oseltamivir Carboxylate Day 3
Time frame: Day 3 (with or after fifth dose): 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
Population: PK population. Number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Oseltamivir: 6 to 12 Years | Cmax of Oseltamivir and Oseltamivir Carboxylate Day 3 | Oseltamivir | 404 ng/mL |
| Oseltamivir: 6 to 12 Years | Cmax of Oseltamivir and Oseltamivir Carboxylate Day 3 | Oseltamivir Carboxylate | 237 ng/mL |
Primary
Cmax of Oseltamivir and Oseltamivir Carboxylate Day 4
Time frame: Day 4: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
Population: PK population. Number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Oseltamivir: 3 to 5 Years | Cmax of Oseltamivir and Oseltamivir Carboxylate Day 4 | Oseltamivir | 915 ng/mL |
| Oseltamivir: 3 to 5 Years | Cmax of Oseltamivir and Oseltamivir Carboxylate Day 4 | Oseltamivir Carboxylate | 549 ng/mL |
Primary
Cmax of Oseltamivir and Oseltamivir Carboxylate Day 5
Time frame: Day 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
Population: PK population. Number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Oseltamivir: 6 to 12 Years | Cmax of Oseltamivir and Oseltamivir Carboxylate Day 5 | Oseltamivir | 403 ng/mL |
| Oseltamivir: 6 to 12 Years | Cmax of Oseltamivir and Oseltamivir Carboxylate Day 5 | Oseltamivir Carboxylate | 408 ng/mL |
Primary
Maximum Observed Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate Day 1
Time frame: Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion
Population: PK population. Number of participants analyzed = participants who were evaluable for this outcome.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir: 6 to 12 Years | Maximum Observed Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate Day 1 | Oseltamivir | 360 nanograms/milliliter (ng/mL) | — |
| Oseltamivir: 6 to 12 Years | Maximum Observed Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate Day 1 | Oseltamivir Carboxylate | 311 nanograms/milliliter (ng/mL) | — |
| Oseltamivir: 3 to 5 Years | Maximum Observed Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate Day 1 | Oseltamivir | 753 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 36.9 |
| Oseltamivir: 3 to 5 Years | Maximum Observed Plasma Concentration (Cmax) of Oseltamivir and Oseltamivir Carboxylate Day 1 | Oseltamivir Carboxylate | 499 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 55.1 |
Secondary
Elimination Rate Constant (ke) of Oseltamivir and Oseltamivir Carboxylate
Time frame: Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
Population: Data not available as no participant was evaluable for specified time-points.
Secondary
Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate
Time frame: Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
Population: PK population. Number of participants analyzed = participants who were evaluable for this outcome, n = number of participants evaluable for specified categories.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir: 6 to 12 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 1: Oseltamivir (n = 1, 3, 0) | 4.40 ng/mL | — |
| Oseltamivir: 6 to 12 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 1: Oseltamivir Carboxylate (n = 1, 3, 0) | 237 ng/mL | — |
| Oseltamivir: 6 to 12 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 2: Oseltamivir (n = 0, 2, 1) | NA ng/mL | — |
| Oseltamivir: 6 to 12 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 2: Oseltamivir Carboxylate (n = 0, 2, 1) | NA ng/mL | — |
| Oseltamivir: 6 to 12 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 3: Oseltamivir (n = 1, 0, 0) | 2.60 ng/mL | — |
| Oseltamivir: 6 to 12 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 3: Oseltamivir Carboxylate (n = 1, 0, 0) | 149 ng/mL | — |
| Oseltamivir: 6 to 12 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 4: Oseltamivir (n = 0, 1, 0) | NA ng/mL | — |
| Oseltamivir: 6 to 12 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 4: Oseltamivir Carboxylate (n = 0, 1, 0) | NA ng/mL | — |
| Oseltamivir: 6 to 12 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 5: Oseltamivir (n = 1, 0, 0) | 15.1 ng/mL | — |
| Oseltamivir: 6 to 12 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 5: Oseltamivir Carboxylate (n = 1, 0, 0) | 339 ng/mL | — |
| Oseltamivir: 3 to 5 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 5: Oseltamivir (n = 1, 0, 0) | NA ng/mL | — |
| Oseltamivir: 3 to 5 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 1: Oseltamivir (n = 1, 3, 0) | 2.41 ng/mL | Geometric Coefficient of Variation 80.6 |
| Oseltamivir: 3 to 5 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 3: Oseltamivir Carboxylate (n = 1, 0, 0) | NA ng/mL | — |
| Oseltamivir: 3 to 5 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 3: Oseltamivir (n = 1, 0, 0) | NA ng/mL | — |
| Oseltamivir: 3 to 5 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 1: Oseltamivir Carboxylate (n = 1, 3, 0) | 308 ng/mL | Geometric Coefficient of Variation 74.4 |
| Oseltamivir: 3 to 5 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 5: Oseltamivir Carboxylate (n = 1, 0, 0) | NA ng/mL | — |
| Oseltamivir: 3 to 5 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 4: Oseltamivir Carboxylate (n = 0, 1, 0) | 549 ng/mL | — |
| Oseltamivir: 3 to 5 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 2: Oseltamivir (n = 0, 2, 1) | 25.2 ng/mL | Geometric Coefficient of Variation 1704911.2 |
| Oseltamivir: 3 to 5 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 4: Oseltamivir (n = 0, 1, 0) | 25.1 ng/mL | — |
| Oseltamivir: 3 to 5 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 2: Oseltamivir Carboxylate (n = 0, 2, 1) | 319 ng/mL | Geometric Coefficient of Variation 0.44 |
| Oseltamivir: 1 to 2 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 4: Oseltamivir Carboxylate (n = 0, 1, 0) | NA ng/mL | — |
| Oseltamivir: 1 to 2 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 2: Oseltamivir Carboxylate (n = 0, 2, 1) | 484 ng/mL | — |
| Oseltamivir: 1 to 2 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 3: Oseltamivir (n = 1, 0, 0) | NA ng/mL | — |
| Oseltamivir: 1 to 2 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 3: Oseltamivir Carboxylate (n = 1, 0, 0) | NA ng/mL | — |
| Oseltamivir: 1 to 2 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 5: Oseltamivir (n = 1, 0, 0) | NA ng/mL | — |
| Oseltamivir: 1 to 2 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 4: Oseltamivir (n = 0, 1, 0) | NA ng/mL | — |
| Oseltamivir: 1 to 2 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 1: Oseltamivir (n = 1, 3, 0) | NA ng/mL | — |
| Oseltamivir: 1 to 2 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 5: Oseltamivir Carboxylate (n = 1, 0, 0) | NA ng/mL | — |
| Oseltamivir: 1 to 2 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 1: Oseltamivir Carboxylate (n = 1, 3, 0) | NA ng/mL | — |
| Oseltamivir: 1 to 2 Years | Last Measurable Plasma Concentration (Clast) of Oseltamivir and Oseltamivir Carboxylate | Day 2: Oseltamivir (n = 0, 2, 1) | 4.76 ng/mL | — |
Secondary
Participants With Greater Than or Equal to (>=) 5-Fold Change in Neuraminidase Inhibition (NAI) Assay 50 Percent (%) Inhibitory Concentration (IC50) Values
IC50 was defined as the concentration that causes 50% inhibition of viral activity. IC50 values were calculated using NAI assay. The 5-fold change was calculated as either \>=5 times change in the NAI IC50 visit value from the Reference value at a visit, \>=5 times change in the NAI IC50 Visit value from the Baseline value.
Time frame: Baseline, Day 1, 6 and 30
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oseltamivir: 6 to 12 Years | 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 |
| Oseltamivir: 6 to 12 Years | 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 |
| Oseltamivir: 6 to 12 Years | 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 |
| Oseltamivir: 3 to 5 Years | 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) | 0 Participants |
| Oseltamivir: 3 to 5 Years | 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 |
| Oseltamivir: 3 to 5 Years | 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) | NA Participants |
| Oseltamivir: 1 to 2 Years | 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 |
| Oseltamivir: 1 to 2 Years | 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 |
| Oseltamivir: 1 to 2 Years | 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) | NA Participants |
| Oseltamivir: 1 to 2 Years | 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) | 0 Participants |
| Oseltamivir: 1 to 2 Years | 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) | NA Participants |
| Oseltamivir: 1 to 2 Years | 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) | NA Participants |
Secondary
Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate
Time frame: Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
Population: PK population. Number of participants analyzed = participants who were evaluable for this outcome, n = number of participants evaluable for specified categories.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir: 6 to 12 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 4: Oseltamivir (n = 0, 1, 0) | NA hours | — |
| Oseltamivir: 6 to 12 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 2: Oseltamivir Carboxylate (n = 0, 2, 1) | NA hours | — |
| Oseltamivir: 6 to 12 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 5: Oseltamivir Carboxylate (n = 1, 0, 0) | 7.92 hours | — |
| Oseltamivir: 6 to 12 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 3: Oseltamivir Carboxylate (n = 1, 0, 0) | 10.13 hours | — |
| Oseltamivir: 6 to 12 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 3: Oseltamivir (n = 1, 0, 0) | 10.13 hours | — |
| Oseltamivir: 6 to 12 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 1: Oseltamivir Carboxylate (n = 1, 3, 0) | 7.42 hours | — |
| Oseltamivir: 6 to 12 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 1: Oseltamivir (n = 1, 3, 0) | 7.42 hours | — |
| Oseltamivir: 6 to 12 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 4: Oseltamivir Carboxylate (n = 0, 1, 0) | NA hours | — |
| Oseltamivir: 6 to 12 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 2: Oseltamivir (n = 0, 2, 1) | NA hours | — |
| Oseltamivir: 6 to 12 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 5: Oseltamivir (n = 1, 0, 0) | 7.92 hours | — |
| Oseltamivir: 3 to 5 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 3: Oseltamivir (n = 1, 0, 0) | NA hours | — |
| Oseltamivir: 3 to 5 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 1: Oseltamivir (n = 1, 3, 0) | 10.50 hours | Geometric Coefficient of Variation 23.4 |
| Oseltamivir: 3 to 5 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 1: Oseltamivir Carboxylate (n = 1, 3, 0) | 11.98 hours | Geometric Coefficient of Variation 0.2 |
| Oseltamivir: 3 to 5 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 2: Oseltamivir (n = 0, 2, 1) | 3.50 hours | Geometric Coefficient of Variation 448.5 |
| Oseltamivir: 3 to 5 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 2: Oseltamivir Carboxylate (n = 0, 2, 1) | 3.50 hours | Geometric Coefficient of Variation 448.47 |
| Oseltamivir: 3 to 5 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 3: Oseltamivir Carboxylate (n = 1, 0, 0) | NA hours | — |
| Oseltamivir: 3 to 5 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 4: Oseltamivir (n = 0, 1, 0) | 8.05 hours | — |
| Oseltamivir: 3 to 5 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 4: Oseltamivir Carboxylate (n = 0, 1, 0) | 8.05 hours | — |
| Oseltamivir: 3 to 5 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 5: Oseltamivir (n = 1, 0, 0) | NA hours | — |
| Oseltamivir: 3 to 5 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 5: Oseltamivir Carboxylate (n = 1, 0, 0) | NA hours | — |
| Oseltamivir: 1 to 2 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 5: Oseltamivir (n = 1, 0, 0) | NA hours | — |
| Oseltamivir: 1 to 2 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 4: Oseltamivir (n = 0, 1, 0) | NA hours | — |
| Oseltamivir: 1 to 2 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 1: Oseltamivir Carboxylate (n = 1, 3, 0) | NA hours | — |
| Oseltamivir: 1 to 2 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 1: Oseltamivir (n = 1, 3, 0) | NA hours | — |
| Oseltamivir: 1 to 2 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 4: Oseltamivir Carboxylate (n = 0, 1, 0) | NA hours | — |
| Oseltamivir: 1 to 2 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 2: Oseltamivir Carboxylate (n = 0, 2, 1) | 12.00 hours | — |
| Oseltamivir: 1 to 2 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 3: Oseltamivir (n = 1, 0, 0) | NA hours | — |
| Oseltamivir: 1 to 2 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 5: Oseltamivir Carboxylate (n = 1, 0, 0) | NA hours | — |
| Oseltamivir: 1 to 2 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 3: Oseltamivir Carboxylate (n = 1, 0, 0) | NA hours | — |
| Oseltamivir: 1 to 2 Years | Time of the Last Measurable Plasma Concentration (Tlast) of Oseltamivir and Oseltamivir Carboxylate | Day 2: Oseltamivir (n = 0, 2, 1) | 12.00 hours | — |
Secondary
Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate
Time frame: Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
Population: PK population. Number of participants analyzed = participants who were evaluable for this outcome, n = number of participants evaluable for specified categories.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir: 6 to 12 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 1: Oseltamivir Carboxylate (n = 1, 3, 0) | 4.00 hours | — |
| Oseltamivir: 6 to 12 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 4: Oseltamivir Carboxylate (n = 0, 1, 0) | NA hours | — |
| Oseltamivir: 6 to 12 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 2: Oseltamivir (n = 0, 1, 1) | NA hours | — |
| Oseltamivir: 6 to 12 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 2: Oseltamivir Carboxylate (n = 0, 1, 1) | NA hours | — |
| Oseltamivir: 6 to 12 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 3: Oseltamivir Carboxylate (n = 1, 0, 0) | 3.05 hours | — |
| Oseltamivir: 6 to 12 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 3: Oseltamivir (n = 1, 0, 0) | 1.05 hours | — |
| Oseltamivir: 6 to 12 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 5: Oseltamivir (n = 1, 0, 0) | 2.00 hours | — |
| Oseltamivir: 6 to 12 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 4: Oseltamivir (n = 0, 1, 0) | NA hours | — |
| Oseltamivir: 6 to 12 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 5: Oseltamivir Carboxylate (n = 1, 0, 0) | 4.08 hours | — |
| Oseltamivir: 6 to 12 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 1: Oseltamivir (n = 1, 3, 0) | 2.00 hours | — |
| Oseltamivir: 3 to 5 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 1: Oseltamivir Carboxylate (n = 1, 3, 0) | 4.61 hours | Geometric Coefficient of Variation 53.3 |
| Oseltamivir: 3 to 5 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 5: Oseltamivir (n = 1, 0, 0) | NA hours | — |
| Oseltamivir: 3 to 5 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 1: Oseltamivir (n = 1, 3, 0) | 1.26 hours | Geometric Coefficient of Variation 41.7 |
| Oseltamivir: 3 to 5 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 2: Oseltamivir (n = 0, 1, 1) | 2.00 hours | — |
| Oseltamivir: 3 to 5 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 4: Oseltamivir Carboxylate (n = 0, 1, 0) | 8.05 hours | — |
| Oseltamivir: 3 to 5 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 3: Oseltamivir Carboxylate (n = 1, 0, 0) | NA hours | — |
| Oseltamivir: 3 to 5 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 2: Oseltamivir Carboxylate (n = 0, 1, 1) | 4.62 hours | — |
| Oseltamivir: 3 to 5 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 5: Oseltamivir Carboxylate (n = 1, 0, 0) | NA hours | — |
| Oseltamivir: 3 to 5 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 4: Oseltamivir (n = 0, 1, 0) | 2.50 hours | — |
| Oseltamivir: 3 to 5 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 3: Oseltamivir (n = 1, 0, 0) | NA hours | — |
| Oseltamivir: 1 to 2 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 5: Oseltamivir Carboxylate (n = 1, 0, 0) | NA hours | — |
| Oseltamivir: 1 to 2 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 3: Oseltamivir Carboxylate (n = 1, 0, 0) | NA hours | — |
| Oseltamivir: 1 to 2 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 4: Oseltamivir (n = 0, 1, 0) | NA hours | — |
| Oseltamivir: 1 to 2 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 4: Oseltamivir Carboxylate (n = 0, 1, 0) | NA hours | — |
| Oseltamivir: 1 to 2 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 5: Oseltamivir (n = 1, 0, 0) | NA hours | — |
| Oseltamivir: 1 to 2 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 3: Oseltamivir (n = 1, 0, 0) | NA hours | — |
| Oseltamivir: 1 to 2 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 1: Oseltamivir (n = 1, 3, 0) | NA hours | — |
| Oseltamivir: 1 to 2 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 1: Oseltamivir Carboxylate (n = 1, 3, 0) | NA hours | — |
| Oseltamivir: 1 to 2 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 2: Oseltamivir (n = 0, 1, 1) | 1.00 hours | — |
| Oseltamivir: 1 to 2 Years | Time to the Maximum Observed Plasma Concentration (Tmax) of Oseltamivir and Oseltamivir Carboxylate | Day 2: Oseltamivir Carboxylate (n = 0, 1, 1) | 6.00 hours | — |
Secondary
Total Clearance of Drug (CL) of Oseltamivir and Oseltamivir Carboxylate
Time frame: Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
Population: Data not available as no participant was evaluable for specified time-points.
Secondary
Volume of Distribution (V) of Oseltamivir and Oseltamivir Carboxylate
Time frame: Day 1: 15 minutes pre-infusion start, 1, 2, 3, 4, 6, 8, 12 hours post start of infusion; Day 2, 3 (with or after fifth dose), 4 or 5: 15 minutes pre-infusion start, 2, 4, 8 hours after start of infusion
Population: Data not collected because of changes in planned analysis, due to early study termination.