Influenza
Conditions
Brief summary
This study will evaluate the safety, pharmacokinetics, and efficacy of baloxavir marboxil compared with oseltamivir in a single influenza episode in otherwise healthy pediatric participants (i.e., 1 to \<12 years of age) with influenza-like symptoms.
Interventions
Baloxavir marboxil will be administered as oral suspension in a single dose on Day 1. Oseltamivir matching placebo will also be administered as oral suspension twice daily (BID) for 5 days.
DRUGOseltamivir
Oseltamivir will be administered as oral suspension BID for 5 days. Participants receiving oseltamivir will also receive baloxavir marboxil matching placebo as oral suspension, single dose on Day 1.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
1 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Aged 1 to \< 12 years at randomization (Day 1). * Written informed consent/assent for study participation obtained from participant's parents or legal guardian, with assent as appropriate by the participant, depending on the patient's level of understanding * Participant able to comply with study requirements, depending on the patient's level of understanding * Participant with a diagnosis of influenza virus infection confirmed by the presence of all of the following: * Fever ≥ 38 degree celsius (tympanic temperature) at screening * At least one respiratory symptom (either cough or nasal congestion) * The time interval between the onset of symptoms and screening is ≤ 48 hours
Exclusion criteria
* Severe symptoms of influenza virus infection requiring inpatient treatment * Concurrent infections requiring systemic antiviral therapy at screening * Require, in the opinion of the investigator, any of the prohibited medication during the study * Previous treatment with peramivir, laninamivir, oseltamivir, zanamivir, or amantadine within 2 weeks prior to screening * Immunization with a live/attenuated influenza vaccine in the 2 weeks prior to randomization * Concomitant treatment with steroids or other immuno-suppressant therapy * Known HIV infection or other immunosuppressive disorder * Uncontrolled renal, vascular, neurologic, or metabolic disease (e.g., diabetes, thyroid disorders, adrenal disease), hepatitis, cirrhosis, or pulmonary disease or participants with known chronic renal failure. * Active cancer at any site * History of organ transplantation * Known allergy to either study drug (i.e., baloxavir marboxil and oseltamivir) or to acetaminophen * Females with child-bearing potential * Participation in a clinical trial within 4 weeks or five half-lives of exposure to an investigational drug prior to screening, whichever is longer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Day 29 | An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A serious adverse event (SAE) is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/ incapacity, is a congenital anomaly/ birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentrations of S-033447 - Sparse PK Population | Days 1 (Post-Dose), 2, 4, 6 and 10 | Results provided by body-weight groups for participants in the Baloxavir Marboxil arm. |
| Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Days 1 (Post-Dose), 2, 4, 6 and 10 | Results provided by body-weight groups for participants in the Baloxavir Marboxil arm. Values below lower limit of quantification (0.5 ng/mL) are set to zero. |
| Plasma Concentrations of S-033447 - Extensive PK Population | Days 1 (Post-Dose), 2, 4, 6 and 10 | Results provided by body-weight groups for participants in the Baloxavir Marboxil arm. Values below lower limit of quantification (0.5 ng/mL) are set to zero. |
| Time to Alleviation of Influenza Signs and Symptoms | Up to Day 15 | Time to alleviation of influenza signs and symptoms is defined as the length of time taken from the start of treatment to the point at which all of the following criteria are met and remain so for at least 21.5 hours: * A score of 0 (no problem) or 1 (minor problem) for cough and nasal symptoms (items 14 and 15 of the Canadian Acute Respiratory Illness and Flu Scale \[CARIFS\]) * A yes response to the following question on the CARIFS: Since the last assessment has the subject been able to return to day care/school, or resume his or her normal daily activity in the same way as performed prior to developing the flu? * First return to afebrile state (tympanic temperature ≤37.2 degree Celsius \[°C\]) |
| Duration of Fever | Up to Day 15 | Length of time taken by participants to return to afebrile state \[tympanic temperature ≤ 37.2°C\] and remaining so for at least 21.5 hours. |
| Duration of Symptoms | Up to Day 15 | The clinical efficacy of baloxavir marboxil is evaluated by duration of symptoms i.e., alleviation of all symptoms as defined by a score of 0 \[no problem\] or 1 \[minor problem\] and remaining so for at least 21.5 hours, for all 18 symptoms specified in the CARIFS questionnaire. |
| Time to Return to Normal Health and Activity | Up to Day 15 | Time to Return to Normal health and activity' is identified by a 'Yes' response to the following question on the CARIFS: Since the last assessment has the patient been able to return to day care/school, or resume his or her normal daily activity in the same way as performed prior to developing the flu? |
| Frequency of Influenza-Related Complications | Up to Day 29 | Influenza related complications include death, hospitalization, radiologically confirmed pneumonia, bronchitis, sinusitis, otitis media, encephalitis/encephalopathy, febrile seizures, myositis. |
| Percentage of Participants With Influenza-Related Complications | Up to Day 29 | Influenza related complications include death, hospitalization, radiologically confirmed pneumonia, bronchitis, sinusitis, otitis media, encephalitis/encephalopathy, febrile seizures, myositis. |
| Percentage of Participants Requiring Antibiotics | Up to Day 29 | — |
| Time to Cessation of Viral Shedding by Virus Titer | Day 1 - Day 29 | Time to cessation of viral shedding by virus titer is defined as the time, in hours, between the initiation of any study treatment and first time when the influenza virus titer is below the limit of detection. |
| Time to Cessation of Viral Shedding by RT-PCR | Day 1 - Day 29 | Time to cessation of viral shedding by RT-PCR, in hours, is defined as the time between the initiation of any study treatment and first time when the virus RNA by RT-PCR is below the limit of detection. |
| Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29 | Baseline, Day 2, 3 (optional), 4, 6, 10, 15 (optional), 29 | Influenza virus titer (log10TCID50/ML) is the quantity of influenza virus in a given volume within the samples obtained from nasal swabs. If influenza virus titer was less than the lower limit of quantification, the virus titer was imputed as 0.749 (log10TCID50/mL). A lower value indicates lower viral titer. |
| Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population | Days 1 (Post-Dose), 2, 4, 6 and 10 | Results provided by body-weight groups for participants in the Baloxavir Marboxil arm. Values below lower limit of quantification (0.5 ng/mL) are set to zero. |
| Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10 | Baseline, Day 2, 3 (optional), 4, 6, 10 | — |
| Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29 | Day 2, 3 (optional), 4, 6, 10, 15 (optional), 29 | — |
| Area Under the Curve in Virus Titer | Day 1 - Day 29 | Area under the curve (AUC) in virus titer was calculated using the trapezoidal method. |
| Area Under the Curve in the Amount of Virus RNA (RT-PCR) | Day 1 - Day 10 | AUC in virus RNA (RT-PCR) is defined as AUC of change from baseline in the amount of virus RNA (RT-PCR) from Day 1 to Day 10. AUC is calculated using the trapezoidal method similar to AUC in virus titer. |
| Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of Baloxavir Marboxil | Up to Day 10 | Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects \<20 kgs and 40 mg dose was used for subjects \>20 kgs. |
| Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of S-033447. | Up to Day 10 | Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects \<20 kgs and 40 mg dose was used for subjects \>20 kgs. |
| Maximum Plasma Concentration (Cmax) of Baloxavir Marboxil | Up to Day 10 | Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects \<20 kgs and 40 mg dose was used for subjects \>20 kgs. |
| Maximum Plasma Concentration (Cmax) of S-033447 | Up to Day 10 | Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects \<20 kgs and 40 mg dose was used for subjects \>20 kgs. |
| Time to Maximum Plasma Concentration (Tmax) of Baloxavir Marboxil | Up to Day 10 | Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects \<20 kgs and 40 mg dose was used for subjects \>20 kgs. |
| Time to Maximum Plasma Concentration (Tmax) of S-033447 | Up to Day 10 | Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects \<20 kgs and 40 mg dose was used for subjects \>20 kgs. |
| Plasma Concentrations of Baloxavir Marboxil by Dosage | 24, 72, 96 and 240 hours post-dose | Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects \<20 kgs and 40 mg dose was used for subjects \>20 kgs. |
| Plasma Concentrations of S-033447 by Dosage | 24, 72, 96 and 240 hours post-dose | Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects \<20 kgs and 40 mg dose was used for subjects \>20 kgs. |
| Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29 | Baseline, Day 2, 3 (optional), 4, 6, 10, 15 (optional), 29 | If the amount of virus RNA was less than the lower limit of quantification, the amount of virus RNA was imputed as 2.18 for flu A and 2.93 for flu B (log10 virus particles/mL) |
Countries
Costa Rica, Israel, Mexico, Poland, Russia, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Baloxavir Marboxil Participants will receive a single oral dose of baloxavir marboxil on Day 1 (based on body weight). Oseltamivir matching placebo will also be administered orally twice daily (BID) for 5 days. | 115 |
| Oseltamivir Participants will receive oseltamivir orally BID for 5 days (based on body weight). Baloxavir marboxil matching placebo will also be administered orally on Day 1 | 58 |
| Total | 173 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Oseltamivir | Baloxavir Marboxil | Total |
|---|---|---|---|
| Age, Continuous | 6.02 years STANDARD_DEVIATION 3.2 | 6.10 years STANDARD_DEVIATION 2.9 | 6.08 years STANDARD_DEVIATION 3 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black or African American | 5 participants | 6 participants | 11 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 27 participants | 52 participants | 79 participants |
| Race/Ethnicity, Customized Multiple | 0 participants | 4 participants | 4 participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 31 participants | 63 participants | 94 participants |
| Race/Ethnicity, Customized Unknown | 1 participants | 5 participants | 6 participants |
| Race/Ethnicity, Customized White | 51 participants | 98 participants | 149 participants |
| Sex: Female, Male Female | 32 Participants | 60 Participants | 92 Participants |
| Sex: Female, Male Male | 26 Participants | 55 Participants | 81 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 115 | 0 / 58 |
| other Total, other adverse events | 15 / 115 | 13 / 58 |
| serious Total, serious adverse events | 0 / 115 | 0 / 58 |
Outcome results
Primary
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A serious adverse event (SAE) is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/ incapacity, is a congenital anomaly/ birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above.
Time frame: Up to Day 29
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baloxavir Marboxil | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events (AEs) | 46.1 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events (SAEs) | 0 percentage of participants |
| Oseltamivir | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events (AEs) | 53.4 percentage of participants |
| Oseltamivir | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events (SAEs) | 0 percentage of participants |
Secondary
Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of Baloxavir Marboxil
Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects \<20 kgs and 40 mg dose was used for subjects \>20 kgs.
Time frame: Up to Day 10
Population: The PK population consists of all participants that have at least one post-dose drug concentration measurement at a scheduled visit time point
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Baloxavir Marboxil | Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of Baloxavir Marboxil | Non-Asian - 2 mg/kg | NA ng.hr/mL |
| Baloxavir Marboxil | Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of Baloxavir Marboxil | Asian - 40 mg | NA ng.hr/mL |
| Baloxavir Marboxil | Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of Baloxavir Marboxil | Non-Asian - 40 mg | NA ng.hr/mL |
Secondary
Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of S-033447.
Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects \<20 kgs and 40 mg dose was used for subjects \>20 kgs.
Time frame: Up to Day 10
Population: The PK population consists of all participants that have at least one post-dose drug concentration measurement at a scheduled visit time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir Marboxil | Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of S-033447. | Non-Asian - 2 mg/kg | 4050 ng.hr/mL | Standard Deviation 2080 |
| Baloxavir Marboxil | Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of S-033447. | Asian - 40 mg | 6600 ng.hr/mL | — |
| Baloxavir Marboxil | Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of S-033447. | Non-Asian - 40 mg | 4390 ng.hr/mL | Standard Deviation 2080 |
Secondary
Area Under the Curve in the Amount of Virus RNA (RT-PCR)
AUC in virus RNA (RT-PCR) is defined as AUC of change from baseline in the amount of virus RNA (RT-PCR) from Day 1 to Day 10. AUC is calculated using the trapezoidal method similar to AUC in virus titer.
Time frame: Day 1 - Day 10
Population: Includes all participants with positive virus RNA by RT-PCR on Day 1 and at least 1 post-baseline test.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baloxavir Marboxil | Area Under the Curve in the Amount of Virus RNA (RT-PCR) | -381.53 log₁₀ VPs/mL*hours | Standard Deviation 338.53 |
| Oseltamivir | Area Under the Curve in the Amount of Virus RNA (RT-PCR) | -353.31 log₁₀ VPs/mL*hours | Standard Deviation 304.01 |
Secondary
Area Under the Curve in Virus Titer
Area under the curve (AUC) in virus titer was calculated using the trapezoidal method.
Time frame: Day 1 - Day 29
Population: Includes all participants with post-baseline Virology assessment and a positive virus titer on Day 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baloxavir Marboxil | Area Under the Curve in Virus Titer | -863.81 log₁₀[TCID₅₀/mL]*hours | Standard Deviation 543.37 |
| Oseltamivir | Area Under the Curve in Virus Titer | -849.29 log₁₀[TCID₅₀/mL]*hours | Standard Deviation 684.43 |
Secondary
Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29
Influenza virus titer (log10TCID50/ML) is the quantity of influenza virus in a given volume within the samples obtained from nasal swabs. If influenza virus titer was less than the lower limit of quantification, the virus titer was imputed as 0.749 (log10TCID50/mL). A lower value indicates lower viral titer.
Time frame: Baseline, Day 2, 3 (optional), 4, 6, 10, 15 (optional), 29
Population: Includes all participants with a positive virus titer on Day 1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir Marboxil | Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29 | Baseline | 4.43 log10TCID50/ML | Standard Deviation 1.36 |
| Baloxavir Marboxil | Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29 | Day 2 | -3.59 log10TCID50/ML | Standard Deviation 1.34 |
| Baloxavir Marboxil | Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29 | Day 3 (optional visit) | -2.83 log10TCID50/ML | Standard Deviation 0.58 |
| Baloxavir Marboxil | Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29 | Day 4 | -3.53 log10TCID50/ML | Standard Deviation 1.38 |
| Baloxavir Marboxil | Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29 | Day 6 | -3.55 log10TCID50/ML | Standard Deviation 1.32 |
| Baloxavir Marboxil | Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29 | Day 10 | -3.66 log10TCID50/ML | Standard Deviation 1.4 |
| Baloxavir Marboxil | Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29 | Day 15 (optional visit) | -3.75 log10TCID50/ML | Standard Deviation 0.54 |
| Baloxavir Marboxil | Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29 | Day 29 | -3.50 log10TCID50/ML | Standard Deviation 1.43 |
| Oseltamivir | Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29 | Day 29 | -3.75 log10TCID50/ML | Standard Deviation 1.19 |
| Oseltamivir | Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29 | Baseline | 4.27 log10TCID50/ML | Standard Deviation 1.48 |
| Oseltamivir | Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29 | Day 6 | -3.52 log10TCID50/ML | Standard Deviation 1.5 |
| Oseltamivir | Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29 | Day 2 | -1.79 log10TCID50/ML | Standard Deviation 1.54 |
| Oseltamivir | Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29 | Day 15 (optional visit) | -3.63 log10TCID50/ML | Standard Deviation 1.45 |
| Oseltamivir | Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29 | Day 3 (optional visit) | -2.63 log10TCID50/ML | Standard Deviation 0.88 |
| Oseltamivir | Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29 | Day 10 | -3.50 log10TCID50/ML | Standard Deviation 1.42 |
| Oseltamivir | Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29 | Day 4 | -3.27 log10TCID50/ML | Standard Deviation 1.54 |
Secondary
Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29
If the amount of virus RNA was less than the lower limit of quantification, the amount of virus RNA was imputed as 2.18 for flu A and 2.93 for flu B (log10 virus particles/mL)
Time frame: Baseline, Day 2, 3 (optional), 4, 6, 10, 15 (optional), 29
Population: Includes all participants with positive virus RNA by RT-PCR on Day 1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir Marboxil | Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29 | Baseline | 6.46 log10 virus particles/mL | Standard Deviation 1.5 |
| Baloxavir Marboxil | Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29 | Day 2 | -1.74 log10 virus particles/mL | Standard Deviation 1.13 |
| Baloxavir Marboxil | Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29 | Day 3 (optional) | -1.78 log10 virus particles/mL | Standard Deviation 1.5 |
| Baloxavir Marboxil | Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29 | Day 4 | -2.40 log10 virus particles/mL | Standard Deviation 1.5 |
| Baloxavir Marboxil | Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29 | Day 6 | -2.73 log10 virus particles/mL | Standard Deviation 1.78 |
| Baloxavir Marboxil | Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29 | Day 10 | -3.55 log10 virus particles/mL | Standard Deviation 1.62 |
| Baloxavir Marboxil | Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29 | Day 15 (optional) | -1.24 log10 virus particles/mL | Standard Deviation 3.06 |
| Baloxavir Marboxil | Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29 | Day 29 | 2.18 log10 virus particles/mL | — |
| Oseltamivir | Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29 | Baseline | 6.86 log10 virus particles/mL | Standard Deviation 1.02 |
| Oseltamivir | Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29 | Day 10 | -3.81 log10 virus particles/mL | Standard Deviation 1.19 |
| Oseltamivir | Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29 | Day 2 | -1.12 log10 virus particles/mL | Standard Deviation 1.12 |
| Oseltamivir | Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29 | Day 6 | -3.32 log10 virus particles/mL | Standard Deviation 1.27 |
| Oseltamivir | Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29 | Day 3 (optional) | -2.21 log10 virus particles/mL | Standard Deviation 0.94 |
| Oseltamivir | Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29 | Day 15 (optional) | -4.44 log10 virus particles/mL | — |
| Oseltamivir | Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29 | Day 4 | -2.47 log10 virus particles/mL | Standard Deviation 1.35 |
Secondary
Duration of Fever
Length of time taken by participants to return to afebrile state \[tympanic temperature ≤ 37.2°C\] and remaining so for at least 21.5 hours.
Time frame: Up to Day 15
Population: Includes all participants with CARIFS Assessment who have had a laboratory confirmation of influenza infection (polymerase chain reaction \[PCR\] result) from any swab sample collected at baseline or during the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baloxavir Marboxil | Duration of Fever | 41.2 hours |
| Oseltamivir | Duration of Fever | 46.8 hours |
Secondary
Duration of Symptoms
The clinical efficacy of baloxavir marboxil is evaluated by duration of symptoms i.e., alleviation of all symptoms as defined by a score of 0 \[no problem\] or 1 \[minor problem\] and remaining so for at least 21.5 hours, for all 18 symptoms specified in the CARIFS questionnaire.
Time frame: Up to Day 15
Population: Includes all participants with CARIFS Assessment who have had a laboratory confirmation of influenza infection (polymerase chain reaction \[PCR\] result) from any swab sample collected at baseline or during the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baloxavir Marboxil | Duration of Symptoms | 66.4 hours |
| Oseltamivir | Duration of Symptoms | 67.9 hours |
Secondary
Frequency of Influenza-Related Complications
Influenza related complications include death, hospitalization, radiologically confirmed pneumonia, bronchitis, sinusitis, otitis media, encephalitis/encephalopathy, febrile seizures, myositis.
Time frame: Up to Day 29
Population: Includes all participants who have had a laboratory confirmation of influenza infection (polymerase chain reaction \[PCR\] result) from any swab sample collected at baseline or during the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baloxavir Marboxil | Frequency of Influenza-Related Complications | Pneumonia | 1 count of events |
| Baloxavir Marboxil | Frequency of Influenza-Related Complications | Death | 0 count of events |
| Baloxavir Marboxil | Frequency of Influenza-Related Complications | Bronchitis | 1 count of events |
| Baloxavir Marboxil | Frequency of Influenza-Related Complications | Sinusitis | 1 count of events |
| Baloxavir Marboxil | Frequency of Influenza-Related Complications | Encephalitis/Encephalopathy | 0 count of events |
| Baloxavir Marboxil | Frequency of Influenza-Related Complications | Total | 6 count of events |
| Baloxavir Marboxil | Frequency of Influenza-Related Complications | Febrile Seizures | 0 count of events |
| Baloxavir Marboxil | Frequency of Influenza-Related Complications | Otitis Media | 3 count of events |
| Baloxavir Marboxil | Frequency of Influenza-Related Complications | Myositis | 0 count of events |
| Baloxavir Marboxil | Frequency of Influenza-Related Complications | Hospitalization | 0 count of events |
| Oseltamivir | Frequency of Influenza-Related Complications | Myositis | 0 count of events |
| Oseltamivir | Frequency of Influenza-Related Complications | Death | 0 count of events |
| Oseltamivir | Frequency of Influenza-Related Complications | Hospitalization | 0 count of events |
| Oseltamivir | Frequency of Influenza-Related Complications | Sinusitis | 0 count of events |
| Oseltamivir | Frequency of Influenza-Related Complications | Otitis Media | 3 count of events |
| Oseltamivir | Frequency of Influenza-Related Complications | Pneumonia | 0 count of events |
| Oseltamivir | Frequency of Influenza-Related Complications | Bronchitis | 0 count of events |
| Oseltamivir | Frequency of Influenza-Related Complications | Encephalitis/Encephalopathy | 0 count of events |
| Oseltamivir | Frequency of Influenza-Related Complications | Febrile Seizures | 1 count of events |
| Oseltamivir | Frequency of Influenza-Related Complications | Total | 4 count of events |
Secondary
Maximum Plasma Concentration (Cmax) of Baloxavir Marboxil
Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects \<20 kgs and 40 mg dose was used for subjects \>20 kgs.
Time frame: Up to Day 10
Population: The PK population consists of all participants that have at least one post-dose drug concentration measurement at a scheduled visit time point
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Baloxavir Marboxil | Maximum Plasma Concentration (Cmax) of Baloxavir Marboxil | Non-Asian - 2 mg/kg | NA ng/mL |
| Baloxavir Marboxil | Maximum Plasma Concentration (Cmax) of Baloxavir Marboxil | Asian - 40 mg | NA ng/mL |
| Baloxavir Marboxil | Maximum Plasma Concentration (Cmax) of Baloxavir Marboxil | Non-Asian - 40 mg | NA ng/mL |
Secondary
Maximum Plasma Concentration (Cmax) of S-033447
Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects \<20 kgs and 40 mg dose was used for subjects \>20 kgs.
Time frame: Up to Day 10
Population: The PK population consists of all participants that have at least one post-dose drug concentration measurement at a scheduled visit time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir Marboxil | Maximum Plasma Concentration (Cmax) of S-033447 | Non-Asian - 2 mg/kg | 109 ng/mL | Standard Deviation 55.3 |
| Baloxavir Marboxil | Maximum Plasma Concentration (Cmax) of S-033447 | Asian - 40 mg | 110 ng/mL | — |
| Baloxavir Marboxil | Maximum Plasma Concentration (Cmax) of S-033447 | Non-Asian - 40 mg | 83.2 ng/mL | Standard Deviation 36.5 |
Secondary
Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29
Time frame: Day 2, 3 (optional), 4, 6, 10, 15 (optional), 29
Population: Includes all participants with positive virus RNA by RT-PCR on Day 1
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baloxavir Marboxil | Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29 | Baseline | 100 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29 | Day 2 | 95.9 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29 | Day 3 (optional) | 100 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29 | Day 4 | 89.9 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29 | Day 6 | 83.1 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29 | Day 10 | 46.5 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29 | Day 15 (optional) | 40.0 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29 | Day 29 | 25.0 percentage of participants |
| Oseltamivir | Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29 | Day 29 | 0 percentage of participants |
| Oseltamivir | Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29 | Baseline | 100 percentage of participants |
| Oseltamivir | Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29 | Day 6 | 75.7 percentage of participants |
| Oseltamivir | Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29 | Day 2 | 100 percentage of participants |
| Oseltamivir | Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29 | Day 15 (optional) | 25.0 percentage of participants |
| Oseltamivir | Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29 | Day 3 (optional) | 100 percentage of participants |
| Oseltamivir | Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29 | Day 10 | 44.1 percentage of participants |
| Oseltamivir | Percentage of Participants Positive by RT-PCR at Day 2, 4, 6, 10, 15, 29 | Day 4 | 97.0 percentage of participants |
Secondary
Percentage of Participants Requiring Antibiotics
Time frame: Up to Day 29
Population: Includes all participants who have had a laboratory confirmation of influenza infection (polymerase chain reaction \[PCR\] result) from any swab sample collected at baseline or during the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baloxavir Marboxil | Percentage of Participants Requiring Antibiotics | Bronchitis | 0 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants Requiring Antibiotics | Pneumonia | 1.2 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants Requiring Antibiotics | Otitis Media | 2.5 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants Requiring Antibiotics | Sinusitis | 1.2 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants Requiring Antibiotics | Total | 4.9 percentage of participants |
| Oseltamivir | Percentage of Participants Requiring Antibiotics | Sinusitis | 0 percentage of participants |
| Oseltamivir | Percentage of Participants Requiring Antibiotics | Total | 4.7 percentage of participants |
| Oseltamivir | Percentage of Participants Requiring Antibiotics | Bronchitis | 0 percentage of participants |
| Oseltamivir | Percentage of Participants Requiring Antibiotics | Otitis Media | 4.7 percentage of participants |
| Oseltamivir | Percentage of Participants Requiring Antibiotics | Pneumonia | 0 percentage of participants |
Secondary
Percentage of Participants With Influenza-Related Complications
Influenza related complications include death, hospitalization, radiologically confirmed pneumonia, bronchitis, sinusitis, otitis media, encephalitis/encephalopathy, febrile seizures, myositis.
Time frame: Up to Day 29
Population: Includes all participants who have had a laboratory confirmation of influenza infection (polymerase chain reaction \[PCR\] result) from any swab sample collected at baseline or during the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baloxavir Marboxil | Percentage of Participants With Influenza-Related Complications | Total | 7.4 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants With Influenza-Related Complications | Death | 0 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants With Influenza-Related Complications | Hospitalization | 0 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants With Influenza-Related Complications | Sinusitis | 1.2 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants With Influenza-Related Complications | Otitis Media | 3.7 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants With Influenza-Related Complications | Pneumonia | 1.2 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants With Influenza-Related Complications | Bronchitis | 1.2 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants With Influenza-Related Complications | Encephalitis/Encephalopathy | 0 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants With Influenza-Related Complications | Febrile Seizures | 0 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants With Influenza-Related Complications | Myositis | 0 percentage of participants |
| Oseltamivir | Percentage of Participants With Influenza-Related Complications | Encephalitis/Encephalopathy | 0 percentage of participants |
| Oseltamivir | Percentage of Participants With Influenza-Related Complications | Total | 7.0 percentage of participants |
| Oseltamivir | Percentage of Participants With Influenza-Related Complications | Pneumonia | 0 percentage of participants |
| Oseltamivir | Percentage of Participants With Influenza-Related Complications | Death | 0 percentage of participants |
| Oseltamivir | Percentage of Participants With Influenza-Related Complications | Myositis | 0 percentage of participants |
| Oseltamivir | Percentage of Participants With Influenza-Related Complications | Hospitalization | 0 percentage of participants |
| Oseltamivir | Percentage of Participants With Influenza-Related Complications | Bronchitis | 0 percentage of participants |
| Oseltamivir | Percentage of Participants With Influenza-Related Complications | Sinusitis | 0 percentage of participants |
| Oseltamivir | Percentage of Participants With Influenza-Related Complications | Febrile Seizures | 2.3 percentage of participants |
| Oseltamivir | Percentage of Participants With Influenza-Related Complications | Otitis Media | 4.7 percentage of participants |
Secondary
Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10
Time frame: Baseline, Day 2, 3 (optional), 4, 6, 10
Population: Includes all participants with a positive virus titer on Day 1
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baloxavir Marboxil | Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10 | Baseline | 100 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10 | Day 2 | 15.6 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10 | Day 3 (optional) | 33.3 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10 | Day 4 | 26.2 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10 | Day 6 | 12.7 percentage of participants |
| Baloxavir Marboxil | Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10 | Day 10 | 1.6 percentage of participants |
| Oseltamivir | Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10 | Day 6 | 5.7 percentage of participants |
| Oseltamivir | Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10 | Baseline | 100 percentage of participants |
| Oseltamivir | Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10 | Day 4 | 29.0 percentage of participants |
| Oseltamivir | Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10 | Day 2 | 75.7 percentage of participants |
| Oseltamivir | Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10 | Day 10 | 0 percentage of participants |
| Oseltamivir | Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10 | Day 3 (optional) | 50.0 percentage of participants |
Secondary
Plasma Concentrations of Baloxavir Marboxil by Dosage
Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects \<20 kgs and 40 mg dose was used for subjects \>20 kgs.
Time frame: 24, 72, 96 and 240 hours post-dose
Population: The PK population consists of all participants that have at least one post-dose drug concentration measurement at a scheduled visit time point
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil by Dosage | 24 - Non-Asian - 2 mg/kg | NA ng/mL |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil by Dosage | 24 - Asian - 40 mg | NA ng/mL |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil by Dosage | 24 - Non-Asian - 40 mg | NA ng/mL |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil by Dosage | 72 - Non-Asian - 2 mg/kg | NA ng/mL |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil by Dosage | 72 - Asian - 40 mg | NA ng/mL |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil by Dosage | 72 - Non-Asian - 40 mg | NA ng/mL |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil by Dosage | 96 - Non-Asian - 2 mg/kg | NA ng/mL |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil by Dosage | 96 - Asian - 40 mg | NA ng/mL |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil by Dosage | 96 - Non-Asian - 40 mg | NA ng/mL |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil by Dosage | 240 - Non-Asian - 2 mg/kg | NA ng/mL |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil by Dosage | 240 - Asian - 40 mg | NA ng/mL |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil by Dosage | 240 - Non-Asian - 40 mg | NA ng/mL |
Secondary
Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population
Results provided by body-weight groups for participants in the Baloxavir Marboxil arm. Values below lower limit of quantification (0.5 ng/mL) are set to zero.
Time frame: Days 1 (Post-Dose), 2, 4, 6 and 10
Population: The PK population consists of all participants that have at least one post-dose drug concentration measurement at a scheduled visit time point. Extensive PK population comprises all participants in the PK population who provided informed consent to intensive PK sampling (additional time points for sample collection on Day 1)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 6 (>=20 kg) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 1, 6 hrs (15 - <20 kg) | 0.000 ng/mL | — |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 2 (15 - <20 kg) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 4 (15 - <20 kg) | 0.000 ng/mL | — |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 6 (15 - <20 kg) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 1, 0.5 - 2 hrs (>=20 kg) | 0.051 ng/mL | Standard Deviation 0.16 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 1, 4 hrs (>=20 kg) | 0.062 ng/mL | Standard Deviation 0.1863 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 1, 6 hrs ((>=20 kg) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 2 (>=20 kg) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 4 (>=20 kg) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 1, 0.5 - 2 hrs (10 - <15 kg) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 1, 4 hrs (10 - <15 kg) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 1, 6 hrs (10 - <15 kg) | 0.000 ng/mL | — |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 2 (10 - <15 kg) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 4 (10 - <15 kg) | 0.000 ng/mL | — |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 6 (10 - <15 kg) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 10 (10 - <15 kg ) | 0.000 ng/mL | — |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 1, 0.5 - 2 hrs (15 - <20 kg) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 1, 4 hrs (15 - <20 kg) | 0.000 ng/mL | — |
| Unknown | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 1, 4 hrs (5 - <10 kg) | — ng/mL | — |
| Unknown | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 1, 6 hrs (5 - <10 kg) | — ng/mL | — |
| Unknown | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 2 (5 - <10 kg) | — ng/mL | — |
| Unknown | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 4 (5 - <10 kg ) | — ng/mL | — |
| Unknown | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 6 (5 - <10 kg ) | — ng/mL | — |
| Unknown | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 10 (5 - <10 kg) | — ng/mL | — |
| Unknown | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 10 (15 - <20 kg) | — ng/mL | — |
| Unknown | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 10 (>=20 kg) | — ng/mL | — |
| Unknown | Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population | Day 1, 0.5 - 2 hrs (5 - <10 kg) | — ng/mL | — |
Secondary
Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population
Results provided by body-weight groups for participants in the Baloxavir Marboxil arm. Values below lower limit of quantification (0.5 ng/mL) are set to zero.
Time frame: Days 1 (Post-Dose), 2, 4, 6 and 10
Population: The pharmacokinetic (PK) population consists of all participants that have at least one post-dose drug concentration measurement at a scheduled visit time point. Sparse PK population comprises all participants in the PK population who did not provide informed consent to intensive PK sampling
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population | >=20 kg (Day 10) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population | 5 - <10 kg (Day 1) | 0.000 ng/mL | — |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population | 5 - <10 kg (Day 2) | 0.000 ng/mL | — |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population | 5 - <10 kg (Day 6) | 0.000 ng/mL | — |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population | 10 - <15 kg (Day 1) | 0.073 ng/mL | Standard Deviation 0.2001 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population | 10 - <15 kg (Day 2) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population | 10 - <15 kg (Day 4) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population | 10 - <15 kg (Day 6) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population | 10 - <15 kg (Day 10) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population | 15 - <20 kg (Day 1) | 0.090 ng/mL | Standard Deviation 0.2386 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population | 15 - <20 kg (Day 2) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population | 15 - <20 kg (Day 4) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population | 15 - <20 kg (Day 6) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population | 15 - <20 kg (Day 10) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population | >=20 kg (Day 1) | 0.048 ng/mL | Standard Deviation 0.1936 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population | >=20 kg (Day 2) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population | >=20 kg (Day 4) | 0.000 ng/mL | Standard Deviation 0 |
| Baloxavir Marboxil | Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population | >=20 kg (Day 6) | 0.000 ng/mL | Standard Deviation 0 |
Secondary
Plasma Concentrations of S-033447 by Dosage
Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects \<20 kgs and 40 mg dose was used for subjects \>20 kgs.
Time frame: 24, 72, 96 and 240 hours post-dose
Population: The PK population consists of all participants that have at least one post-dose drug concentration measurement at a scheduled visit time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir Marboxil | Plasma Concentrations of S-033447 by Dosage | 24 - Non-Asian - 2 mg/kg | 55.7 ng/mL | Standard Deviation 28.1 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 by Dosage | 24 - Asian - 40 mg | 75.2 ng/mL | — |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 by Dosage | 24 - Non-Asian - 40 mg | 53.2 ng/mL | Standard Deviation 22.4 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 by Dosage | 72 - Non-Asian - 2 mg/kg | 13.2 ng/mL | Standard Deviation 7.15 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 by Dosage | 72 - Asian - 40 mg | 28.9 ng/mL | — |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 by Dosage | 72 - Non-Asian - 40 mg | 17.90 ng/mL | Standard Deviation 8.91 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 by Dosage | 96 - Non-Asian - 2 mg/kg | 7.61 ng/mL | Standard Deviation 4.4 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 by Dosage | 96 - Asian - 40 mg | 19.0 ng/mL | — |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 by Dosage | 96 - Non-Asian - 40 mg | 11.3 ng/mL | Standard Deviation 6.16 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 by Dosage | 240 - Non-Asian - 2 mg/kg | 0.989 ng/mL | Standard Deviation 0.887 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 by Dosage | 240 - Asian - 40 mg | 3.31 ng/mL | — |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 by Dosage | 240 - Non-Asian - 40 mg | 1.85 ng/mL | Standard Deviation 1.4 |
Secondary
Plasma Concentrations of S-033447 - Extensive PK Population
Results provided by body-weight groups for participants in the Baloxavir Marboxil arm. Values below lower limit of quantification (0.5 ng/mL) are set to zero.
Time frame: Days 1 (Post-Dose), 2, 4, 6 and 10
Population: The PK population consists of all participants that have at least one post-dose drug concentration measurement at a scheduled visit time point. Extensive PK population comprises all participants in the PK population who provided informed consent to intensive PK sampling (additional time points for sample collection on Day 1)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Extensive PK Population | Day 6 (>=20 kg) | 6.240 ng/mL | Standard Deviation 3.3702 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Extensive PK Population | Day 1, 6 hrs (15 - <20 kg) | 80.300 ng/mL | — |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Extensive PK Population | Day 2 (15 - <20 kg) | 42.640 ng/mL | Standard Deviation 47.6024 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Extensive PK Population | Day 4 (15 - <20 kg) | 12.200 ng/mL | — |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Extensive PK Population | Day 6 (15 - <20 kg) | 2.663 ng/mL | Standard Deviation 1.5387 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Extensive PK Population | Day 1, 0.5 - 2 hrs (>=20 kg) | 19.923 ng/mL | Standard Deviation 27.098 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Extensive PK Population | Day 1, 4 hrs (>=20 kg) | 69.198 ng/mL | Standard Deviation 55.722 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Extensive PK Population | Day 1, 6 hrs ((>=20 kg) | 65.527 ng/mL | Standard Deviation 43.0799 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Extensive PK Population | Day 2 (>=20 kg) | 57.980 ng/mL | Standard Deviation 37.8922 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Extensive PK Population | Day 4 (>=20 kg) | 21.775 ng/mL | Standard Deviation 3.7968 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Extensive PK Population | Day 1, 0.5 - 2 hrs (10 - <15 kg) | 10.768 ng/mL | Standard Deviation 14.7987 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Extensive PK Population | Day 1, 4 hrs (10 - <15 kg) | 49.500 ng/mL | Standard Deviation 13.0108 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Extensive PK Population | Day 1, 6 hrs (10 - <15 kg) | 41.000 ng/mL | — |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Extensive PK Population | Day 2 (10 - <15 kg) | 28.933 ng/mL | Standard Deviation 14.7514 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Extensive PK Population | Day 4 (10 - <15 kg) | 2.230 ng/mL | — |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Extensive PK Population | Day 6 (10 - <15 kg) | 3.131 ng/mL | Standard Deviation 2.2828 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Extensive PK Population | Day 10 (10 - <15 kg ) | 0.000 ng/mL | — |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Extensive PK Population | Day 1, 0.5 - 2 hrs (15 - <20 kg) | 93.883 ng/mL | Standard Deviation 152.5431 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Extensive PK Population | Day 1, 4 hrs (15 - <20 kg) | 72.900 ng/mL | — |
| Unknown | Plasma Concentrations of S-033447 - Extensive PK Population | Day 1, 4 hrs (5 - <10 kg) | — ng/mL | — |
| Unknown | Plasma Concentrations of S-033447 - Extensive PK Population | Day 1, 6 hrs (5 - <10 kg) | — ng/mL | — |
| Unknown | Plasma Concentrations of S-033447 - Extensive PK Population | Day 2 (5 - <10 kg) | — ng/mL | — |
| Unknown | Plasma Concentrations of S-033447 - Extensive PK Population | Day 4 (5 - <10 kg ) | — ng/mL | — |
| Unknown | Plasma Concentrations of S-033447 - Extensive PK Population | Day 6 (5 - <10 kg ) | — ng/mL | — |
| Unknown | Plasma Concentrations of S-033447 - Extensive PK Population | Day 10 (5 - <10 kg) | — ng/mL | — |
| Unknown | Plasma Concentrations of S-033447 - Extensive PK Population | Day 10 (15 - <20 kg) | — ng/mL | — |
| Unknown | Plasma Concentrations of S-033447 - Extensive PK Population | Day 10 (>=20 kg) | — ng/mL | — |
| Unknown | Plasma Concentrations of S-033447 - Extensive PK Population | Day 1, 0.5 - 2 hrs (5 - <10 kg) | — ng/mL | — |
Secondary
Plasma Concentrations of S-033447 - Sparse PK Population
Results provided by body-weight groups for participants in the Baloxavir Marboxil arm.
Time frame: Days 1 (Post-Dose), 2, 4, 6 and 10
Population: The PK population consists of all participants that have at least one post-dose drug concentration measurement at a scheduled visit time point. Sparse PK population comprises all participants in the PK population who did not provide informed consent to intensive PK sampling
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Sparse PK Population | 5 - <10 kg (Day 1) | 45.700 ng/mL | — |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Sparse PK Population | 5 - <10 kg (Day 2) | 45.800 ng/mL | — |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Sparse PK Population | 5 - <10 kg (Day 6) | 3.110 ng/mL | — |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Sparse PK Population | 10 - <15 kg (Day 1) | 49.084 ng/mL | Standard Deviation 53.6689 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Sparse PK Population | 10 - <15 kg (Day 2) | 42.900 ng/mL | Standard Deviation 16.5227 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Sparse PK Population | 10 - <15 kg (Day 4) | 9.233 ng/mL | Standard Deviation 5.3879 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Sparse PK Population | 10 - <15 kg (Day 6) | 2.965 ng/mL | Standard Deviation 1.648 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Sparse PK Population | 10 - <15 kg (Day 10) | 0.367 ng/mL | Standard Deviation 0.6351 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Sparse PK Population | 15 - <20 kg (Day 1) | 64.160 ng/mL | Standard Deviation 73.632 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Sparse PK Population | 15 - <20 kg (Day 2) | 67.729 ng/mL | Standard Deviation 46.7346 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Sparse PK Population | 15 - <20 kg (Day 4) | 15.840 ng/mL | Standard Deviation 10.8285 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Sparse PK Population | 15 - <20 kg (Day 6) | 4.829 ng/mL | Standard Deviation 3.6562 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Sparse PK Population | 15 - <20 kg (Day 10) | 1.110 ng/mL | Standard Deviation 1.9226 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Sparse PK Population | >=20 kg (Day 1) | 29.899 ng/mL | Standard Deviation 26.1558 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Sparse PK Population | >=20 kg (Day 2) | 56.287 ng/mL | Standard Deviation 40.4073 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Sparse PK Population | >=20 kg (Day 4) | 18.674 ng/mL | Standard Deviation 11.2179 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Sparse PK Population | >=20 kg (Day 6) | 7.397 ng/mL | Standard Deviation 5.053 |
| Baloxavir Marboxil | Plasma Concentrations of S-033447 - Sparse PK Population | >=20 kg (Day 10) | 3.953 ng/mL | Standard Deviation 2.2536 |
Secondary
Time to Alleviation of Influenza Signs and Symptoms
Time to alleviation of influenza signs and symptoms is defined as the length of time taken from the start of treatment to the point at which all of the following criteria are met and remain so for at least 21.5 hours: * A score of 0 (no problem) or 1 (minor problem) for cough and nasal symptoms (items 14 and 15 of the Canadian Acute Respiratory Illness and Flu Scale \[CARIFS\]) * A yes response to the following question on the CARIFS: Since the last assessment has the subject been able to return to day care/school, or resume his or her normal daily activity in the same way as performed prior to developing the flu? * First return to afebrile state (tympanic temperature ≤37.2 degree Celsius \[°C\])
Time frame: Up to Day 15
Population: Includes all participants with CARIFS Assessment who have had a laboratory confirmation of influenza infection (polymerase chain reaction \[PCR\] result) from any swab sample collected at baseline or during the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baloxavir Marboxil | Time to Alleviation of Influenza Signs and Symptoms | 138.1 hours |
| Oseltamivir | Time to Alleviation of Influenza Signs and Symptoms | 150.0 hours |
Secondary
Time to Cessation of Viral Shedding by RT-PCR
Time to cessation of viral shedding by RT-PCR, in hours, is defined as the time between the initiation of any study treatment and first time when the virus RNA by RT-PCR is below the limit of detection.
Time frame: Day 1 - Day 29
Population: Includes all participants with post-baseline Virology assessment and a positive virus RNA by RT-PCR on Day 1. Participants whose virus RNA did not reach the limit by the last observation time point are treated as censored at that time point.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baloxavir Marboxil | Time to Cessation of Viral Shedding by RT-PCR | 242.5 hours |
| Oseltamivir | Time to Cessation of Viral Shedding by RT-PCR | 238.9 hours |
Secondary
Time to Cessation of Viral Shedding by Virus Titer
Time to cessation of viral shedding by virus titer is defined as the time, in hours, between the initiation of any study treatment and first time when the influenza virus titer is below the limit of detection.
Time frame: Day 1 - Day 29
Population: Includes all participants with post-baseline Virology assessment and a positive virus titer on Day 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baloxavir Marboxil | Time to Cessation of Viral Shedding by Virus Titer | 24.2 hours |
| Oseltamivir | Time to Cessation of Viral Shedding by Virus Titer | 75.8 hours |
Secondary
Time to Maximum Plasma Concentration (Tmax) of Baloxavir Marboxil
Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects \<20 kgs and 40 mg dose was used for subjects \>20 kgs.
Time frame: Up to Day 10
Population: The PK population consists of all participants that have at least one post-dose drug concentration measurement at a scheduled visit time point
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Baloxavir Marboxil | Time to Maximum Plasma Concentration (Tmax) of Baloxavir Marboxil | Non-Asian - 2 mg/kg | NA hours |
| Baloxavir Marboxil | Time to Maximum Plasma Concentration (Tmax) of Baloxavir Marboxil | Asian - 40 mg | NA hours |
| Baloxavir Marboxil | Time to Maximum Plasma Concentration (Tmax) of Baloxavir Marboxil | Non-Asian - 40 mg | NA hours |
Secondary
Time to Maximum Plasma Concentration (Tmax) of S-033447
Dose groups correspond to body-weight groups. 2mg/kg dose was used for subjects \<20 kgs and 40 mg dose was used for subjects \>20 kgs.
Time frame: Up to Day 10
Population: The PK population consists of all participants that have at least one post-dose drug concentration measurement at a scheduled visit time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir Marboxil | Time to Maximum Plasma Concentration (Tmax) of S-033447 | Non-Asian - 2 mg/kg | 4.12 hours | Standard Deviation 2.07 |
| Baloxavir Marboxil | Time to Maximum Plasma Concentration (Tmax) of S-033447 | Asian - 40 mg | 5.50 hours | — |
| Baloxavir Marboxil | Time to Maximum Plasma Concentration (Tmax) of S-033447 | Non-Asian - 40 mg | 5.55 hours | Standard Deviation 3.79 |
Secondary
Time to Return to Normal Health and Activity
Time to Return to Normal health and activity' is identified by a 'Yes' response to the following question on the CARIFS: Since the last assessment has the patient been able to return to day care/school, or resume his or her normal daily activity in the same way as performed prior to developing the flu?
Time frame: Up to Day 15
Population: Includes all participants with CARIFS Assessment who have had a laboratory confirmation of influenza infection (polymerase chain reaction \[PCR\] result) from any swab sample collected at baseline or during the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baloxavir Marboxil | Time to Return to Normal Health and Activity | 116.5 hours |
| Oseltamivir | Time to Return to Normal Health and Activity | 111.6 hours |