Influenza
Conditions
Brief summary
This study will assess the pharmacokinetics/pharmacodynamics and safety of oseltamivir \[Tamiflu\] therapy in infants less than 1 year of age with influenza diagnosed in the 96 hours prior to the first dose. Patients age 3-12 months will receive 3 mg/kg, 1-3 months will receive 2.5 mg/kg, and birth to 1 month will receive 2 mg/kg twice a day for a total of 10 doses. Patients positive for influenza virus on Day 6 will be eligible to receive continued study treatment for an additional 10 doses (5 days). The anticipated time on study treatment is 4 weeks, and the target sample size is 65-85 male and female infants.
Interventions
DRUGTamiflu
oral repeating dose
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 12 Months
Healthy volunteers
No
Inclusion criteria
* infants \</=12 months of age * laboratory confirmed diagnosis of influenza within 96 hours prior to first dose * influenza symptoms for \</=96 hours prior to first dose
Exclusion criteria
* preterm infants less than 40 weeks (corrected for gestational age) * weight less than 5th percentile for age (corrected for gestational age) * concurrent gastrointestinal conditions that preclude enteric absorption of the drug * bronchopulmonary dysplasia/chronic lung disease on assisted ventilation at time of enrollment * active or uncontrolled respiratory, cardiac, hepatic, CNS or renal disease at baseline * symptomatic inborn errors of metabolism
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Steady-state Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Oseltamivir and Oseltamivir Carboxylate | 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1 | Oseltamivir carboxylate is active metabolite of oseltamivir. AUC0-12 was estimated for oseltamivir and oseltamivir carboxylate by linear trapezoidal rule |
| Steady-state Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1 | Oseltamivir carboxylate is an active metabolite of oseltamivir. Cmax was estimated for both oseltamivir and Oseltamivir carboxylate by non-compartmental analysis. |
| Steady-state Minimum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1 | Oseltamivir carboxylate is active metabolite of oseltamivir. Cmin was estimated for both oseltamivir and oseltamivir carboxylate by non-compartmental analysis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Plasma Clearance as a Function of Bioavailability and Apparent Plasma Clearance of the Metabolite as a Function of Bioavailability (CLm/F) of Oseltamivir and Oseltamivir Carboxylate | 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1 | Oseltamivir carboxylate is active metabolite of oseltamivir. CL/F was calculated as dose/AUCinf, where AUCinf represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity |
| The Volume of Distribution as a Function of Bioavailability of Oseltamivir and Oseltamivir Carboxylate | 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1 | Oseltamivir carboxylate is active metabolite of oseltamivir. V/F is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. |
| Clast of Oseltamivir and Oseltamivir Carboxylate | 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1 | The last measurable plasma concentration of oseltamivir and oseltamivir carboxylate was the last quantifiable concentration of oseltamivir or oseltamivir carboxylate, respectively. |
| Time of the Last Measurable Plasma Concentration for Oseltamivir and Oseltamivir Carboxylate | 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1 | Oseltamivir carboxylate is an active metabolite of oseltamivir. |
| Number of Participants With Change From Baseline in Neurological Assessment Scores | Baseline (Day 1); Day 3 for who received two does on Day 1 or Day 4 for who received one dose on Day 1; Day 6, Day 11, Day 18, Day 30 | Neurological assessment was performed to assess the mental state of the participants through two scales: Infant face scale and Glasgow coma scale. Each scale consists of 3 subscales: eye opening (ranging 1 to 4), verbal response (ranging 1 to 5), and motor responses (ranging 1 to 6). The final score is the sum of these ranges and is scored between 3 and 15. 3 being the worst, and 15 the best. Change from baseline is change of final score post-baseline minus the final score at baseline. |
| Time to the Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1 | Oseltamivir carboxylate is an active metabolite of oseltamivir.Tmax was estimated using non-compartmental methods |
| Number of Participants With Virus Shedding by Virus Type | Baseline (Day 1), Day3/4, Day 6, Day 11, Day 18+/-2 days, Day 30+/-2 days | The viral titer was measured by culture and reported in log10 (50% tissue culture infective dose \[TCID50\]). The viral load was analyzed by PCR and reported as log10 particles/mL. The number of patients positive for viral shedding by virus sub-type was measured on specified days from baseline to last visit on Day 30. |
| Time to Resolution of Fever in Participants With Fever at the Baseline | Days 1 to 11; Day 18; Day 30 | This was performed for all participants who had fever at baseline. Fever is defined as body temperature \>37.0 degree Celsius. Rectal temperature is converted by subtracting 1 degree Celsius. Time to Resolution of Fever was defined as the time from the initiation of treatment to first time the afebrile state was reached and maintained for at least 21.5 hours, where afebrile state was defined as axillary temperature ≤ 37 degree Celsius. |
| Percentage of Participants With Decline of Body Temperature to the Afebrile State | Baseline (Day 1), Day3/4, Day 6, Day 11, Day 18+/-2 days, Day 30+/-2 days | This was performed for all participants who had fever at baseline Fever is defined as body temperature \>37.0ºC. Rectal temperature is converted by subtracting 1 ºC. The rate of decline of body temperature was calculated as the slope of body temperature between the baseline temperature and the 1st temperature below 37°C. Participants with decline in body temperature were considered to have no fever; however, participants who did not show any decline in body temperature were considered to have persisting fever. |
| Number of Participants With Adverse Events, Serious Adverse Events and Secondary Illness | Up to 3 days after the last dose of oseltamivir (Approximately 14 days) | An Adverse Event (AEs) is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An Serious Adverse Event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. Secondary illnesses were influenza disease-related events, namely bronchitis, pneumonia, otitis media, and sinusitis that resolved without sequelae. Adverse events, serious adverse events, and secondary illness are reported for on-treatment period (from the first dose of oseltamivir upto 3 days after the last dose of oseltamivir \[Approximately 14 days\]. |
| Number of Participants Showing Within-patient Variability in Vital Signs | Post baseline, Day 3, 4, 6, 11, 18+/- 2 days, 30+/-2 days | Systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, and heart rate were examined for any consistent within-patient post-baseline changes. |
| Median Time to Cessation of Viral Shedding in Participants With Positive Culture at Baseline | Days 1, 3 or 4, 6, 11, 18, and 30 | Median time to cessation of viral shedding was calculated for all patients with positive by culture / by polymerase chain reaction (PCR) at baseline using all data points between the start of the treatment and the 1st time point of negative culture without subsequent positive culture results. These time-to event analyses were only performed for the viral titre. |
| Apparent Elimination Half Life of Oseltamivir and Oseltamivir Carboxylate | 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/-15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1 | Elimination half-life is defined as the time required for elimination of a drug to half its plasma concentration and was computed using non-compartmental method |
| Apparent First-order Elimination Rate Constant of Oseltamivir and Oseltamivir Carboxylate | 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1 | Oseltamivir carboxylate is active metabolite of oseltamivir.The apparent first-order elimination rate constant (Lambda Z) was determined by linear regression analysis of terminal data points. A minimum of 3 data points were used for lambda Z estimation. By reporting tool convention, if n\<3, no summary statistics were calculated |
Countries
Belgium, France, Germany, Italy, Poland, Spain
Participant flow
Recruitment details
The study was conducted across 11 centers in Spain, Italy, France, Germany, Belgium, and Poland from 10 January 2011 to 04 April 2012. A total of 65 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Oseltamivir 3 mg/kg Participants aged 91 to \<365 days received oral suspension of oseltamivir 3 mg/kg twice a day for 5 days. | 40 |
| Oseltamivir 2.5 mg/kg Participants of age 31 to 90 days received oral suspension of oseltamivir 2.5 mg/kg twice a day for 5 days | 20 |
| Oseltamivir 2 mg/kg Participants of age 0 to 30 days received oral suspension of oseltamivir 2 mg/kg twice a day for 5 days | 5 |
| Total | 65 |
Baseline characteristics
| Characteristic | Oseltamivir 3 mg/kg | Oseltamivir 2.5 mg/kg | Oseltamivir 2 mg/kg | Total |
|---|---|---|---|---|
| Age, Continuous | 223.2 Days STANDARD_DEVIATION 79.41 | 57.0 Days STANDARD_DEVIATION 17.24 | 25.2 Days STANDARD_DEVIATION 5.36 | 156.8 Days STANDARD_DEVIATION 105.62 |
| Sex: Female, Male Female | 19 Participants | 8 Participants | 2 Participants | 29 Participants |
| Sex: Female, Male Male | 21 Participants | 12 Participants | 3 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 40 | 12 / 20 | 2 / 5 |
| serious Total, serious adverse events | 3 / 40 | 1 / 20 | 0 / 5 |
Outcome results
Primary
Steady-state Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Oseltamivir and Oseltamivir Carboxylate
Oseltamivir carboxylate is active metabolite of oseltamivir. AUC0-12 was estimated for oseltamivir and oseltamivir carboxylate by linear trapezoidal rule
Time frame: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Population: Pharmacokinetic (PK) population included all treated participants with at least one blood sample evaluable for drug concentration level and who adhered to the protocol. n = participants with evaluable drug concentration
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir 3 mg/kg | Steady-state Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir, n=37, 17, 4 | 277 hour (h)*nanogram(ng)/milliliter (mL) | Geometric Coefficient of Variation 36.2 |
| Oseltamivir 3 mg/kg | Steady-state Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate, n=18,11, 2 | 4990 hour (h)*nanogram(ng)/milliliter (mL) | Geometric Coefficient of Variation 27.4 |
| Oseltamivir 2.5 mg/kg | Steady-state Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir, n=37, 17, 4 | 194 hour (h)*nanogram(ng)/milliliter (mL) | Geometric Coefficient of Variation 47.8 |
| Oseltamivir 2.5 mg/kg | Steady-state Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate, n=18,11, 2 | 4920 hour (h)*nanogram(ng)/milliliter (mL) | Geometric Coefficient of Variation 35.3 |
| Oseltamivir 2 mg/kg | Steady-state Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir, n=37, 17, 4 | 142 hour (h)*nanogram(ng)/milliliter (mL) | Geometric Coefficient of Variation 48.8 |
| Oseltamivir 2 mg/kg | Steady-state Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate, n=18,11, 2 | NA hour (h)*nanogram(ng)/milliliter (mL) | — |
Primary
Steady-state Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate
Oseltamivir carboxylate is an active metabolite of oseltamivir. Cmax was estimated for both oseltamivir and Oseltamivir carboxylate by non-compartmental analysis.
Time frame: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Population: Pharmacokinetic (PK) population included all treated participants with at least one blood sample evaluable for drug concentration level and who adhered to the protocol. n = participants with evaluable drug concentration
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir 3 mg/kg | Steady-state Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir | 80.8 ng/mL | Geometric Coefficient of Variation 47 |
| Oseltamivir 3 mg/kg | Steady-state Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate | 464 ng/mL | Geometric Coefficient of Variation 37.7 |
| Oseltamivir 2.5 mg/kg | Steady-state Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir | 62.5 ng/mL | Geometric Coefficient of Variation 69.1 |
| Oseltamivir 2.5 mg/kg | Steady-state Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate | 530 ng/mL | Geometric Coefficient of Variation 33.1 |
| Oseltamivir 2 mg/kg | Steady-state Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir | 25.2 ng/mL | Geometric Coefficient of Variation 211.6 |
| Oseltamivir 2 mg/kg | Steady-state Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate | 501 ng/mL | Geometric Coefficient of Variation 22.2 |
Primary
Steady-state Minimum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate
Oseltamivir carboxylate is active metabolite of oseltamivir. Cmin was estimated for both oseltamivir and oseltamivir carboxylate by non-compartmental analysis
Time frame: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Population: Pharmacokinetic (PK) population included all treated participants with at least one blood sample evaluable for drug concentration level and who adhered to the protocol. n = participants with evaluable drug concentration.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir 3 mg/kg | Steady-state Minimum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir | 2.88 ng/mL | Geometric Coefficient of Variation 65.4 |
| Oseltamivir 3 mg/kg | Steady-state Minimum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate | 238 ng/mL | Geometric Coefficient of Variation 43.8 |
| Oseltamivir 2.5 mg/kg | Steady-state Minimum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir | 2.09 ng/mL | Geometric Coefficient of Variation 52.6 |
| Oseltamivir 2.5 mg/kg | Steady-state Minimum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate | 248 ng/mL | Geometric Coefficient of Variation 51.5 |
| Oseltamivir 2 mg/kg | Steady-state Minimum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir | 2.56 ng/mL | Geometric Coefficient of Variation 90 |
| Oseltamivir 2 mg/kg | Steady-state Minimum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate | 169 ng/mL | Geometric Coefficient of Variation 96.4 |
Secondary
Apparent Elimination Half Life of Oseltamivir and Oseltamivir Carboxylate
Elimination half-life is defined as the time required for elimination of a drug to half its plasma concentration and was computed using non-compartmental method
Time frame: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/-15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Population: Pharmacokinetic (PK) population included all treated participants with at least one blood sample evaluable for drug concentration level and who adhered to the protocol. n = participants with evaluable drug concentration
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir 3 mg/kg | Apparent Elimination Half Life of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir, n= 37, 17, 4 | 2.02 hours | Geometric Coefficient of Variation 38.5 |
| Oseltamivir 3 mg/kg | Apparent Elimination Half Life of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate, n=18, 11, 2 | 9.45 hours | Geometric Coefficient of Variation 53.3 |
| Oseltamivir 2.5 mg/kg | Apparent Elimination Half Life of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir, n= 37, 17, 4 | 2.01 hours | Geometric Coefficient of Variation 49.3 |
| Oseltamivir 2.5 mg/kg | Apparent Elimination Half Life of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate, n=18, 11, 2 | 11.3 hours | Geometric Coefficient of Variation 92.7 |
| Oseltamivir 2 mg/kg | Apparent Elimination Half Life of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir, n= 37, 17, 4 | 1.66 hours | Geometric Coefficient of Variation 41.5 |
| Oseltamivir 2 mg/kg | Apparent Elimination Half Life of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate, n=18, 11, 2 | NA hours | — |
Secondary
Apparent First-order Elimination Rate Constant of Oseltamivir and Oseltamivir Carboxylate
Oseltamivir carboxylate is active metabolite of oseltamivir.The apparent first-order elimination rate constant (Lambda Z) was determined by linear regression analysis of terminal data points. A minimum of 3 data points were used for lambda Z estimation. By reporting tool convention, if n\<3, no summary statistics were calculated
Time frame: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Population: Pharmacokinetic (PK) population included all treated participants with at least one blood sample evaluable for drug concentration level and who adhered to the protocol.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir 3 mg/kg | Apparent First-order Elimination Rate Constant of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir, n= 33, 11, 4 | 0.349 1/hour | Geometric Coefficient of Variation 39.9 |
| Oseltamivir 3 mg/kg | Apparent First-order Elimination Rate Constant of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate, n=17, 7, 2 | 0.0735 1/hour | Geometric Coefficient of Variation 55.2 |
| Oseltamivir 2.5 mg/kg | Apparent First-order Elimination Rate Constant of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir, n= 33, 11, 4 | 0.338 1/hour | Geometric Coefficient of Variation 52.9 |
| Oseltamivir 2.5 mg/kg | Apparent First-order Elimination Rate Constant of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate, n=17, 7, 2 | 0.0475 1/hour | Geometric Coefficient of Variation 110.6 |
| Oseltamivir 2 mg/kg | Apparent First-order Elimination Rate Constant of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir, n= 33, 11, 4 | 0.418 1/hour | Geometric Coefficient of Variation 41.5 |
| Oseltamivir 2 mg/kg | Apparent First-order Elimination Rate Constant of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate, n=17, 7, 2 | NA 1/hour | — |
Secondary
Clast of Oseltamivir and Oseltamivir Carboxylate
The last measurable plasma concentration of oseltamivir and oseltamivir carboxylate was the last quantifiable concentration of oseltamivir or oseltamivir carboxylate, respectively.
Time frame: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Population: Pharmacokinetic (PK) population included all treated patients with at least one blood sample evaluable for drug concentration level and who were adhered to the protocol
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir 3 mg/kg | Clast of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir | 262 ng/mL | Geometric Coefficient of Variation 39.2 |
| Oseltamivir 3 mg/kg | Clast of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate | 3800 ng/mL | Geometric Coefficient of Variation 50.1 |
| Oseltamivir 2.5 mg/kg | Clast of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir | 176 ng/mL | Geometric Coefficient of Variation 58.3 |
| Oseltamivir 2.5 mg/kg | Clast of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate | 4410 ng/mL | Geometric Coefficient of Variation 34 |
| Oseltamivir 2 mg/kg | Clast of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir | 84.3 ng/mL | Geometric Coefficient of Variation 154.4 |
| Oseltamivir 2 mg/kg | Clast of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate | 3940 ng/mL | Geometric Coefficient of Variation 28.2 |
Secondary
Median Time to Cessation of Viral Shedding in Participants With Positive Culture at Baseline
Median time to cessation of viral shedding was calculated for all patients with positive by culture / by polymerase chain reaction (PCR) at baseline using all data points between the start of the treatment and the 1st time point of negative culture without subsequent positive culture results. These time-to event analyses were only performed for the viral titre.
Time frame: Days 1, 3 or 4, 6, 11, 18, and 30
Population: Pharmacodynamic Analysis Population consisted of all enrolled participants with a positive influenza infection confirmed by culture or PCR at baseline or anytime during the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oseltamivir 3 mg/kg | Median Time to Cessation of Viral Shedding in Participants With Positive Culture at Baseline | 228.5 hours |
| Oseltamivir 2.5 mg/kg | Median Time to Cessation of Viral Shedding in Participants With Positive Culture at Baseline | 113.0 hours |
| Oseltamivir 2 mg/kg | Median Time to Cessation of Viral Shedding in Participants With Positive Culture at Baseline | 113.0 hours |
p-value: =0.16695% CI: [113, 230]Wilcoxon (Mann-Whitney)
Secondary
Number of Participants Showing Within-patient Variability in Vital Signs
Systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, and heart rate were examined for any consistent within-patient post-baseline changes.
Time frame: Post baseline, Day 3, 4, 6, 11, 18+/- 2 days, 30+/-2 days
Population: Safety population included all treated participants with at least one post-baseline safety assessment. Due to the small numbers of participants and the extent of influenza induced variability, changes in vital sign patterns cannot be detected.
Secondary
Number of Participants With Adverse Events, Serious Adverse Events and Secondary Illness
An Adverse Event (AEs) is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. An Serious Adverse Event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. Secondary illnesses were influenza disease-related events, namely bronchitis, pneumonia, otitis media, and sinusitis that resolved without sequelae. Adverse events, serious adverse events, and secondary illness are reported for on-treatment period (from the first dose of oseltamivir upto 3 days after the last dose of oseltamivir \[Approximately 14 days\].
Time frame: Up to 3 days after the last dose of oseltamivir (Approximately 14 days)
Population: Safety population included all treated participants with at least one post-baseline safety assessment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oseltamivir 3 mg/kg | Number of Participants With Adverse Events, Serious Adverse Events and Secondary Illness | Participants with any SAE | 3 Participants |
| Oseltamivir 3 mg/kg | Number of Participants With Adverse Events, Serious Adverse Events and Secondary Illness | Participants with any AE | 13 Participants |
| Oseltamivir 3 mg/kg | Number of Participants With Adverse Events, Serious Adverse Events and Secondary Illness | Participants with secondary illness | 0 Participants |
| Oseltamivir 2.5 mg/kg | Number of Participants With Adverse Events, Serious Adverse Events and Secondary Illness | Participants with any SAE | 1 Participants |
| Oseltamivir 2.5 mg/kg | Number of Participants With Adverse Events, Serious Adverse Events and Secondary Illness | Participants with any AE | 12 Participants |
| Oseltamivir 2.5 mg/kg | Number of Participants With Adverse Events, Serious Adverse Events and Secondary Illness | Participants with secondary illness | 1 Participants |
| Oseltamivir 2 mg/kg | Number of Participants With Adverse Events, Serious Adverse Events and Secondary Illness | Participants with any AE | 2 Participants |
| Oseltamivir 2 mg/kg | Number of Participants With Adverse Events, Serious Adverse Events and Secondary Illness | Participants with secondary illness | 0 Participants |
| Oseltamivir 2 mg/kg | Number of Participants With Adverse Events, Serious Adverse Events and Secondary Illness | Participants with any SAE | 0 Participants |
Secondary
Number of Participants With Change From Baseline in Neurological Assessment Scores
Neurological assessment was performed to assess the mental state of the participants through two scales: Infant face scale and Glasgow coma scale. Each scale consists of 3 subscales: eye opening (ranging 1 to 4), verbal response (ranging 1 to 5), and motor responses (ranging 1 to 6). The final score is the sum of these ranges and is scored between 3 and 15. 3 being the worst, and 15 the best. Change from baseline is change of final score post-baseline minus the final score at baseline.
Time frame: Baseline (Day 1); Day 3 for who received two does on Day 1 or Day 4 for who received one dose on Day 1; Day 6, Day 11, Day 18, Day 30
Population: Safety population included all treated participants with at least one post-baseline safety assessment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oseltamivir 3 mg/kg | Number of Participants With Change From Baseline in Neurological Assessment Scores | With change in infant face scale measurement score | 0 participants |
| Oseltamivir 3 mg/kg | Number of Participants With Change From Baseline in Neurological Assessment Scores | With change in Glasgow coma scale assessment score | 0 participants |
| Oseltamivir 2.5 mg/kg | Number of Participants With Change From Baseline in Neurological Assessment Scores | With change in infant face scale measurement score | 2 participants |
| Oseltamivir 2.5 mg/kg | Number of Participants With Change From Baseline in Neurological Assessment Scores | With change in Glasgow coma scale assessment score | 1 participants |
| Oseltamivir 2 mg/kg | Number of Participants With Change From Baseline in Neurological Assessment Scores | With change in infant face scale measurement score | 0 participants |
| Oseltamivir 2 mg/kg | Number of Participants With Change From Baseline in Neurological Assessment Scores | With change in Glasgow coma scale assessment score | 0 participants |
Secondary
Number of Participants With Virus Shedding by Virus Type
The viral titer was measured by culture and reported in log10 (50% tissue culture infective dose \[TCID50\]). The viral load was analyzed by PCR and reported as log10 particles/mL. The number of patients positive for viral shedding by virus sub-type was measured on specified days from baseline to last visit on Day 30.
Time frame: Baseline (Day 1), Day3/4, Day 6, Day 11, Day 18+/-2 days, Day 30+/-2 days
Population: Pharmacodynamic Analysis Population consisted of all enrolled participants with a positive influenza infection confirmed by culture or PCR at baseline or anytime during the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oseltamivir 3 mg/kg | Number of Participants With Virus Shedding by Virus Type | Day 30 +-2 | 0 Participants |
| Oseltamivir 3 mg/kg | Number of Participants With Virus Shedding by Virus Type | Baseline | 32 Participants |
| Oseltamivir 3 mg/kg | Number of Participants With Virus Shedding by Virus Type | Day 11 | 32 Participants |
| Oseltamivir 3 mg/kg | Number of Participants With Virus Shedding by Virus Type | Day 3 or 4 | 20 Participants |
| Oseltamivir 3 mg/kg | Number of Participants With Virus Shedding by Virus Type | Day 6 | 12 Participants |
| Oseltamivir 3 mg/kg | Number of Participants With Virus Shedding by Virus Type | Day 18 +-2 | 0 Participants |
| Oseltamivir 2.5 mg/kg | Number of Participants With Virus Shedding by Virus Type | Day 6 | 4 Participants |
| Oseltamivir 2.5 mg/kg | Number of Participants With Virus Shedding by Virus Type | Day 18 +-2 | 1 Participants |
| Oseltamivir 2.5 mg/kg | Number of Participants With Virus Shedding by Virus Type | Day 30 +-2 | 0 Participants |
| Oseltamivir 2.5 mg/kg | Number of Participants With Virus Shedding by Virus Type | Day 3 or 4 | 5 Participants |
| Oseltamivir 2.5 mg/kg | Number of Participants With Virus Shedding by Virus Type | Day 11 | 9 Participants |
| Oseltamivir 2.5 mg/kg | Number of Participants With Virus Shedding by Virus Type | Baseline | 10 Participants |
| Oseltamivir 2 mg/kg | Number of Participants With Virus Shedding by Virus Type | Day 30 +-2 | 0 Participants |
| Oseltamivir 2 mg/kg | Number of Participants With Virus Shedding by Virus Type | Baseline | 14 Participants |
| Oseltamivir 2 mg/kg | Number of Participants With Virus Shedding by Virus Type | Day 3 or 4 | 14 Participants |
| Oseltamivir 2 mg/kg | Number of Participants With Virus Shedding by Virus Type | Day 11 | 16 Participants |
| Oseltamivir 2 mg/kg | Number of Participants With Virus Shedding by Virus Type | Day 18 +-2 | 0 Participants |
| Oseltamivir 2 mg/kg | Number of Participants With Virus Shedding by Virus Type | Day 6 | 7 Participants |
Secondary
Percentage of Participants With Decline of Body Temperature to the Afebrile State
This was performed for all participants who had fever at baseline Fever is defined as body temperature \>37.0ºC. Rectal temperature is converted by subtracting 1 ºC. The rate of decline of body temperature was calculated as the slope of body temperature between the baseline temperature and the 1st temperature below 37°C. Participants with decline in body temperature were considered to have no fever; however, participants who did not show any decline in body temperature were considered to have persisting fever.
Time frame: Baseline (Day 1), Day3/4, Day 6, Day 11, Day 18+/-2 days, Day 30+/-2 days
Population: Pharmacodynamic Analysis Population consisted of all enrolled participants with a positive influenza infection confirmed by culture or PCR at baseline or anytime during the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oseltamivir 3 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Baseline, n=33, 11, 4, decline | 36 percentage of participants |
| Oseltamivir 3 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Baseline, n=33, 11, 4, no decline | 64 percentage of participants |
| Oseltamivir 3 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 4, n=33, 11, 4, decline | 94 percentage of participants |
| Oseltamivir 3 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 4, n=33, 11, 4, no decline | 6 percentage of participants |
| Oseltamivir 3 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 11, n=33, 11, 4, decline | 97 percentage of participants |
| Oseltamivir 3 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 11, n=33, 11, 4, no decline | 3 percentage of participants |
| Oseltamivir 3 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 18, n=16, 5, 1, decline | 94 percentage of participants |
| Oseltamivir 3 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 18, n=16, 5, 1, no decline | 6 percentage of participants |
| Oseltamivir 3 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 30, n=31, 9, 4, decline | 97 percentage of participants |
| Oseltamivir 3 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 30, n=31, 9, 4, no decline | 3 percentage of participants |
| Oseltamivir 2.5 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 30, n=31, 9, 4, decline | 89 percentage of participants |
| Oseltamivir 2.5 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Baseline, n=33, 11, 4, decline | 55 percentage of participants |
| Oseltamivir 2.5 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 11, n=33, 11, 4, no decline | 0 percentage of participants |
| Oseltamivir 2.5 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 30, n=31, 9, 4, no decline | 11 percentage of participants |
| Oseltamivir 2.5 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Baseline, n=33, 11, 4, no decline | 45 percentage of participants |
| Oseltamivir 2.5 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 4, n=33, 11, 4, no decline | 9 percentage of participants |
| Oseltamivir 2.5 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 18, n=16, 5, 1, no decline | 0 percentage of participants |
| Oseltamivir 2.5 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 4, n=33, 11, 4, decline | 91 percentage of participants |
| Oseltamivir 2.5 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 18, n=16, 5, 1, decline | 100 percentage of participants |
| Oseltamivir 2.5 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 11, n=33, 11, 4, decline | 100 percentage of participants |
| Oseltamivir 2 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 18, n=16, 5, 1, decline | 100 percentage of participants |
| Oseltamivir 2 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 4, n=33, 11, 4, no decline | 0 percentage of participants |
| Oseltamivir 2 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 11, n=33, 11, 4, decline | 100 percentage of participants |
| Oseltamivir 2 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 11, n=33, 11, 4, no decline | 0 percentage of participants |
| Oseltamivir 2 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 30, n=31, 9, 4, decline | 100 percentage of participants |
| Oseltamivir 2 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 18, n=16, 5, 1, no decline | 0 percentage of participants |
| Oseltamivir 2 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Baseline, n=33, 11, 4, decline | 25 percentage of participants |
| Oseltamivir 2 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 30, n=31, 9, 4, no decline | 0 percentage of participants |
| Oseltamivir 2 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Baseline, n=33, 11, 4, no decline | 75 percentage of participants |
| Oseltamivir 2 mg/kg | Percentage of Participants With Decline of Body Temperature to the Afebrile State | Day 4, n=33, 11, 4, decline | 100 percentage of participants |
Secondary
The Volume of Distribution as a Function of Bioavailability of Oseltamivir and Oseltamivir Carboxylate
Oseltamivir carboxylate is active metabolite of oseltamivir. V/F is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Time frame: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Population: Pharmacokinetic (PK) population included all treated participants with at least one blood sample evaluable for drug concentration level and who adhered to the protocol. n = participants with evaluable drug concentration.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir 3 mg/kg | The Volume of Distribution as a Function of Bioavailability of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir, n= 37, 17, 4 | 234000 mL | Geometric Coefficient of Variation 66.2 |
| Oseltamivir 3 mg/kg | The Volume of Distribution as a Function of Bioavailability of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate, n=18,11, 2 | 53700 mL | Geometric Coefficient of Variation 78.1 |
| Oseltamivir 2.5 mg/kg | The Volume of Distribution as a Function of Bioavailability of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir, n= 37, 17, 4 | 183000 mL | Geometric Coefficient of Variation 87.9 |
| Oseltamivir 2.5 mg/kg | The Volume of Distribution as a Function of Bioavailability of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate, n=18,11, 2 | 35400 mL | Geometric Coefficient of Variation 96.5 |
| Oseltamivir 2 mg/kg | The Volume of Distribution as a Function of Bioavailability of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir, n= 37, 17, 4 | 121000 mL | Geometric Coefficient of Variation 69.8 |
| Oseltamivir 2 mg/kg | The Volume of Distribution as a Function of Bioavailability of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate, n=18,11, 2 | NA mL | — |
Secondary
Time of the Last Measurable Plasma Concentration for Oseltamivir and Oseltamivir Carboxylate
Oseltamivir carboxylate is an active metabolite of oseltamivir.
Time frame: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Population: Pharmacokinetic (PK) population included all treated participants with at least one blood sample evaluable for drug concentration level and who adhered to the protocol.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir 3 mg/kg | Time of the Last Measurable Plasma Concentration for Oseltamivir and Oseltamivir Carboxylate | Oseltamivir | 9.23 hours | Geometric Coefficient of Variation 30.1 |
| Oseltamivir 3 mg/kg | Time of the Last Measurable Plasma Concentration for Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate | 10.11 hours | Geometric Coefficient of Variation 21.2 |
| Oseltamivir 2.5 mg/kg | Time of the Last Measurable Plasma Concentration for Oseltamivir and Oseltamivir Carboxylate | Oseltamivir | 8.53 hours | Geometric Coefficient of Variation 32.9 |
| Oseltamivir 2.5 mg/kg | Time of the Last Measurable Plasma Concentration for Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate | 10.64 hours | Geometric Coefficient of Variation 5.4 |
| Oseltamivir 2 mg/kg | Time of the Last Measurable Plasma Concentration for Oseltamivir and Oseltamivir Carboxylate | Oseltamivir | 6.94 hours | Geometric Coefficient of Variation 24.2 |
| Oseltamivir 2 mg/kg | Time of the Last Measurable Plasma Concentration for Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate | 10.45 hours | Geometric Coefficient of Variation 5.3 |
Secondary
Time to Resolution of Fever in Participants With Fever at the Baseline
This was performed for all participants who had fever at baseline. Fever is defined as body temperature \>37.0 degree Celsius. Rectal temperature is converted by subtracting 1 degree Celsius. Time to Resolution of Fever was defined as the time from the initiation of treatment to first time the afebrile state was reached and maintained for at least 21.5 hours, where afebrile state was defined as axillary temperature ≤ 37 degree Celsius.
Time frame: Days 1 to 11; Day 18; Day 30
Population: Pharmacodynamic Analysis Population consisted of all enrolled participants with a positive influenza infection confirmed by culture or PCR at baseline or anytime during the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Oseltamivir 3 mg/kg | Time to Resolution of Fever in Participants With Fever at the Baseline | 12.0 hours |
| Oseltamivir 2.5 mg/kg | Time to Resolution of Fever in Participants With Fever at the Baseline | 20.5 hours |
| Oseltamivir 2 mg/kg | Time to Resolution of Fever in Participants With Fever at the Baseline | 24.0 hours |
p-value: =0.05995% CI: [12, 20]Wilcoxon (Mann-Whitney)
Secondary
Time to the Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate
Oseltamivir carboxylate is an active metabolite of oseltamivir.Tmax was estimated using non-compartmental methods
Time frame: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Population: Pharmacokinetic (PK) population included all treated participants with at least one blood sample evaluable for drug concentration level and who adhered to the protocol. n = participants with evaluable drug concentration
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Oseltamivir 3 mg/kg | Time to the Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir | 1.08 hours |
| Oseltamivir 3 mg/kg | Time to the Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate | 5.04 hours |
| Oseltamivir 2.5 mg/kg | Time to the Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir | 1.08 hours |
| Oseltamivir 2.5 mg/kg | Time to the Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate | 2.88 hours |
| Oseltamivir 2 mg/kg | Time to the Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir | 1.08 hours |
| Oseltamivir 2 mg/kg | Time to the Maximum Observed Plasma Concentration of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate | 5.83 hours |
Secondary
Total Plasma Clearance as a Function of Bioavailability and Apparent Plasma Clearance of the Metabolite as a Function of Bioavailability (CLm/F) of Oseltamivir and Oseltamivir Carboxylate
Oseltamivir carboxylate is active metabolite of oseltamivir. CL/F was calculated as dose/AUCinf, where AUCinf represents the area under the concentration-time curve of the analyte in plasma over the time interval from zero extrapolated to infinity
Time frame: 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 3 if two doses taken on Day 1 or 15 minutes pre-dose; 1 hour +/- 15 minutes, 2-3, 5-7, 10-12 hours post-dose on Day 4 if one dose taken on Day 1
Population: Pharmacokinetic (PK) population included all treated participants with at least one blood sample evaluable for drug concentration level and who adhered to the protocol. n = participants with evaluable drug concentration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Oseltamivir 3 mg/kg | Total Plasma Clearance as a Function of Bioavailability and Apparent Plasma Clearance of the Metabolite as a Function of Bioavailability (CLm/F) of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir, n= 37, 17, 4 | 80500 mL/hour | Standard Deviation 42.8 |
| Oseltamivir 3 mg/kg | Total Plasma Clearance as a Function of Bioavailability and Apparent Plasma Clearance of the Metabolite as a Function of Bioavailability (CLm/F) of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate, n=18,11, 2 | 3940 mL/hour | Standard Deviation 38.8 |
| Oseltamivir 2.5 mg/kg | Total Plasma Clearance as a Function of Bioavailability and Apparent Plasma Clearance of the Metabolite as a Function of Bioavailability (CLm/F) of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir, n= 37, 17, 4 | 63000 mL/hour | Standard Deviation 63.7 |
| Oseltamivir 2.5 mg/kg | Total Plasma Clearance as a Function of Bioavailability and Apparent Plasma Clearance of the Metabolite as a Function of Bioavailability (CLm/F) of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate, n=18,11, 2 | 2180 mL/hour | Standard Deviation 54.86 |
| Oseltamivir 2 mg/kg | Total Plasma Clearance as a Function of Bioavailability and Apparent Plasma Clearance of the Metabolite as a Function of Bioavailability (CLm/F) of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir, n= 37, 17, 4 | 50600 mL/hour | Standard Deviation 39.9 |
| Oseltamivir 2 mg/kg | Total Plasma Clearance as a Function of Bioavailability and Apparent Plasma Clearance of the Metabolite as a Function of Bioavailability (CLm/F) of Oseltamivir and Oseltamivir Carboxylate | Oseltamivir carboxylate, n=18,11, 2 | NA mL/hour | — |