Study to Assess the Safety, Pharmacokinetics, and Efficacy of Baloxavir Marboxil in Healthy Pediatric Participants With Influenza-Like Symptoms

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03629184
• Collaborator: (none)
• Enrollment: 173
• Locations: 37
• Arms: 2
• Actual Duration (Months): 4.4
• Patients Per Site: 4.7
• Patients Per Site Per Month: 1.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Drug: Baloxavir Marboxil; Drug: Oseltamivir	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 173 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Active (Oseltamivir)-Controlled Study to Assess the Safety, Pharmacokinetics, and Efficacy of Baloxavir Marboxil in Otherwise Healthy Pediatric Patients 1 to <12 Years of Age With Influenza-Like Symptoms
• Actual Study Start Date: Nov 20, 2018
• Actual Primary Completion Date: Apr 3, 2019
• Actual Study Completion Date: Apr 3, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Baloxavir Marboxil; 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.
Active Comparator: 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	Drug: Oseltamivir; 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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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])

6. 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.

7. 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.

8. 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?"

9. 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.

10. 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.

11. Percentage of Participants Requiring Antibiotics [Up to Day 29]

12. 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.

13. 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.

14. 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.

15. 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)

16. Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10 [Baseline, Day 2, 3 (optional), 4, 6, 10]

17. 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]

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

25. 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.

26. 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.

27. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 11 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Central Alabama Research; Pediatrics	Birmingham	Alabama	United States	35209
2	Harrisburg Family Medical Center	Harrisburg	Arkansas	United States	72432
3	The Children's Clinic of Jonesboro, P.A.	Jonesboro	Arkansas	United States	72401
4	The Probe Medical Research	Los Angeles	California	United States	90004
5	Orange County Research Institute	Ontario	California	United States	91762
6	Khruz Biotechnology Research Institute	San Diego	California	United States	92102
7	Avanza Medical Research Center	Pensacola	Florida	United States	32503
8	Clinical Research Prime	Idaho Falls	Idaho	United States	83404
9	Cotton O'Neil Clinic; Stormont-Vail Hlth Care	Topeka	Kansas	United States	66606
10	Kentucky Pediatric Research Center	Bardstown	Kentucky	United States	40004
11	Spiegel, Craig	Bridgeton	Missouri	United States	63044
12	Meridian Clinical Research, Llc	Omaha	Nebraska	United States	68134
13	Machuca Family Medicine	Las Vegas	Nevada	United States	89104
14	OnSite Clinical Solutions LLC	Charlotte	North Carolina	United States	28203
15	Montgomery Medical Research /Frontier Clinical Research	Smithfield	North Carolina	United States	15478
16	Ohio Pediatric Research Association	Dayton	Ohio	United States	45414
17	Coastal Pediatric Research	Charleston	South Carolina	United States	29414
18	AFC Urgent Care- Cleveland	Cleveland	Tennessee	United States	37312
19	Holston Medical Group	Kingsport	Tennessee	United States	37660
20	Oak Cliff Research Company, LLC	Dallas	Texas	United States	75243
21	HD Research Corp	Houston	Texas	United States	77004
22	Mercury Clinical Research	Houston	Texas	United States	77036-3316
23	Tekton Research	San Antonio	Texas	United States	78240
24	DM Clinical Research	Tomball	Texas	United States	77375
25	ClinPoint Trials	Waxahachie	Texas	United States	75165
26	FirstMed East (J Lewis Research)	Salt Lake City	Utah	United States	84121
27	Advanced Clinical Research - Jordan Ridge Family Medicine	Salt Lake City	Utah	United States	84123
28	ICIMED Instituto de Investigación en Ciencias Médicas	San Jose		Costa Rica	10108
29	Clalit Health Services- Pediatric Ambulatory Clinic; Pediatric Ambulatory Clinic	Petach Tikva		Israel	4931807
30	Hospital San Jose; Centro de investigacion y transferencia en salud del Tec de Monterrey	Monterrey, N.L		Mexico	64710
31	Wojewodzki Szpital Obserwacyjno-Zakazny; Oddział Pediatrii, Chorób Infekcyjnych i Hepatologii	Bydgoszcz		Poland	85-030
32	NZOZ Vitamed	Bydgoszcz		Poland	85-079
33	Prywatny Gabinet Lekarski	Debica		Poland	39-200
34	NZLA Michalkowice Jarosz i partnerzy Spolka Lekarska	Siemianowice Śląskie		Poland	41-103
35	MC Gepatolog	Samara		Russian Federation	443100
36	Complejo Hospitalario Universitario de Santiago (CHUS); Area Asistencial Integrada de Pediatría	Santiago de Compostela	LA Coruña	Spain	15706
37	Hospital Universitario 12 de Octubre; Servicio de Pediatria	Madrid		Spain	28041

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol - Jun 29, 2018
• Statistical Analysis Plan - May 24, 2019

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT03629184
• Other Study ID Numbers: CP40563; 2018-002169-21
• First Posted: Aug 14, 2018
• Last Update Posted: Apr 29, 2020
• Last Verified: Apr 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Influenza, Human; Oseltamivir; Baloxavir

Study Results

Participant Flow

Arm/Group Title	Baloxavir Marboxil	Oseltamivir
Arm/Group Description	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.	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
Period Title: Overall Study
STARTED	115	58
COMPLETED	112	57
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	Baloxavir Marboxil	Oseltamivir	Total
Arm/Group Description	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.	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	Total of all reporting groups
Overall Participants	115	58	173
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	6.10 (2.90)	6.02 (3.20)	6.08 (3.00)
Sex: Female, Male (Count of Participants)
Female	60 52.2%	32 55.2%	92 53.2%
Male	55 47.8%	26 44.8%	81 46.8%
Race/Ethnicity, Customized (participants) [Number]
American Indian or Alaska Native	1 0.9%	0 0%	1 0.6%
Asian	1 0.9%	0 0%	1 0.6%
Black or African American	6 5.2%	5 8.6%	11 6.4%
Native Hawaiian or other Pacific Islander	0 0%	1 1.7%	1 0.6%
White	98 85.2%	51 87.9%	149 86.1%
Multiple	4 3.5%	0 0%	4 2.3%
Unknown	5 4.3%	1 1.7%	6 3.5%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	52 45.2%	27 46.6%	79 45.7%
Not Hispanic or Latino	63 54.8%	31 53.4%	94 54.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baloxavir Marboxil	Oseltamivir
Arm/Group Description	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.	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
Measure Participants	115	58
Adverse Events (AEs)	46.1 40.1%	53.4 92.1%
Serious Adverse Events (SAEs)	0 0%	0 0%

2. Secondary Outcome

Title	Plasma Concentrations of Baloxavir Marboxil - Sparse PK Population
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Baloxavir Marboxil
Arm/Group Description	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.
Measure Participants	88
5 - <10 kg (Day 1)	0.000 (NA)
5 - <10 kg (Day 2)	0.000 (NA)
5 - <10 kg (Day 6)	0.000 (NA)
10 - <15 kg (Day 1)	0.073 (0.2001)
10 - <15 kg (Day 2)	0.000 (0.0000)
10 - <15 kg (Day 4)	0.000 (0.0000)
10 - <15 kg (Day 6)	0.000 (0.0000)
10 - <15 kg (Day 10)	0.000 (0.0000)
15 - <20 kg (Day 1)	0.090 (0.2386)
15 - <20 kg (Day 2)	0.000 (0.0000)
15 - <20 kg (Day 4)	0.000 (0.0000)
15 - <20 kg (Day 6)	0.000 (0.0000)
15 - <20 kg (Day 10)	0.000 (0.0000)
>=20 kg (Day 1)	0.048 (0.1936)
>=20 kg (Day 2)	0.000 (0.0000)
>=20 kg (Day 4)	0.000 (0.0000)
>=20 kg (Day 6)	0.000 (0.0000)
>=20 kg (Day 10)	0.000 (0.0000)

3. Secondary Outcome

Title	Plasma Concentrations of S-033447 - Sparse PK Population
Description	Results provided by body-weight groups for participants in the Baloxavir Marboxil arm.
Time Frame	Days 1 (Post-Dose), 2, 4, 6 and 10

Outcome Measure Data

Analysis Population Description

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/Group Title	Baloxavir Marboxil
Arm/Group Description	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.
Measure Participants	88
5 - <10 kg (Day 1)	45.700 (NA)
5 - <10 kg (Day 2)	45.800 (NA)
5 - <10 kg (Day 6)	3.110 (NA)
10 - <15 kg (Day 1)	49.084 (53.6689)
10 - <15 kg (Day 2)	42.900 (16.5227)
10 - <15 kg (Day 4)	9.233 (5.3879)
10 - <15 kg (Day 6)	2.965 (1.6480)
10 - <15 kg (Day 10)	0.367 (0.6351)
15 - <20 kg (Day 1)	64.160 (73.6320)
15 - <20 kg (Day 2)	67.729 (46.7346)
15 - <20 kg (Day 4)	15.840 (10.8285)
15 - <20 kg (Day 6)	4.829 (3.6562)
15 - <20 kg (Day 10)	1.110 (1.9226)
>=20 kg (Day 1)	29.899 (26.1558)
>=20 kg (Day 2)	56.287 (40.4073)
>=20 kg (Day 4)	18.674 (11.2179)
>=20 kg (Day 6)	7.397 (5.0530)
>=20 kg (Day 10)	3.953 (2.2536)

4. Secondary Outcome

Title	Plasma Concentrations of Baloxavir Marboxil - Extensive PK Population
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Baloxavir Marboxil
Arm/Group Description	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.
Measure Participants	19
Day 1, 0.5 - 2 hrs (10 - <15 kg)	0.000 (0.0000)
Day 1, 4 hrs (10 - <15 kg)	0.000 (0.0000)
Day 1, 6 hrs (10 - <15 kg)	0.000 (NA)
Day 2 (10 - <15 kg)	0.000 (0.0000)
Day 4 (10 - <15 kg)	0.000 (NA)
Day 6 (10 - <15 kg)	0.000 (0.0000)
Day 10 (10 - <15 kg )	0.000 (NA)
Day 1, 0.5 - 2 hrs (15 - <20 kg)	0.000 (0.0000)
Day 1, 4 hrs (15 - <20 kg)	0.000 (NA)
Day 1, 6 hrs (15 - <20 kg)	0.000 (NA)
Day 2 (15 - <20 kg)	0.000 (0.0000)
Day 4 (15 - <20 kg)	0.000 (NA)
Day 6 (15 - <20 kg)	0.000 (0.0000)
Day 1, 0.5 - 2 hrs (>=20 kg)	0.051 (0.1600)
Day 1, 4 hrs (>=20 kg)	0.062 (0.1863)
Day 1, 6 hrs ((>=20 kg)	0.000 (0.0000)
Day 2 (>=20 kg)	0.000 (0.0000)
Day 4 (>=20 kg)	0.000 (0.0000)
Day 6 (>=20 kg)	0.000 (0.0000)

5. Secondary Outcome

Title	Plasma Concentrations of S-033447 - Extensive PK Population
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Baloxavir Marboxil
Arm/Group Description	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.
Measure Participants	19
Day 1, 0.5 - 2 hrs (10 - <15 kg)	10.768 (14.7987)
Day 1, 4 hrs (10 - <15 kg)	49.500 (13.0108)
Day 1, 6 hrs (10 - <15 kg)	41.000 (NA)
Day 2 (10 - <15 kg)	28.933 (14.7514)
Day 4 (10 - <15 kg)	2.230 (NA)
Day 6 (10 - <15 kg)	3.131 (2.2828)
Day 10 (10 - <15 kg )	0.000 (NA)
Day 1, 0.5 - 2 hrs (15 - <20 kg)	93.883 (152.5431)
Day 1, 4 hrs (15 - <20 kg)	72.900 (NA)
Day 1, 6 hrs (15 - <20 kg)	80.300 (NA)
Day 2 (15 - <20 kg)	42.640 (47.6024)
Day 4 (15 - <20 kg)	12.200 (NA)
Day 6 (15 - <20 kg)	2.663 (1.5387)
Day 1, 0.5 - 2 hrs (>=20 kg)	19.923 (27.0980)
Day 1, 4 hrs (>=20 kg)	69.198 (55.7220)
Day 1, 6 hrs ((>=20 kg)	65.527 (43.0799)
Day 2 (>=20 kg)	57.980 (37.8922)
Day 4 (>=20 kg)	21.775 (3.7968)
Day 6 (>=20 kg)	6.240 (3.3702)

6. Secondary Outcome

Title	Time to Alleviation of Influenza Signs and Symptoms
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Baloxavir Marboxil	Oseltamivir
Arm/Group Description	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.	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
Measure Participants	80	43
Median (95% Confidence Interval) [hours]	138.1	150.0

7. Secondary Outcome

Title	Duration of Fever
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Baloxavir Marboxil	Oseltamivir
Arm/Group Description	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.	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
Measure Participants	80	43
Median (95% Confidence Interval) [hours]	41.2	46.8

8. Secondary Outcome

Title	Duration of Symptoms
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Baloxavir Marboxil	Oseltamivir
Arm/Group Description	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.	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
Measure Participants	80	43
Median (95% Confidence Interval) [hours]	66.4	67.9

9. Secondary Outcome

Title	Time to Return to Normal Health and Activity
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Baloxavir Marboxil	Oseltamivir
Arm/Group Description	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.	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
Measure Participants	80	43
Median (95% Confidence Interval) [hours]	116.5	111.6

10. Secondary Outcome

Title	Frequency of Influenza-Related Complications
Description	Influenza related complications include death, hospitalization, radiologically confirmed pneumonia, bronchitis, sinusitis, otitis media, encephalitis/encephalopathy, febrile seizures, myositis.
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description

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/Group Title	Baloxavir Marboxil	Oseltamivir
Arm/Group Description	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.	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
Measure Participants	81	43
Total	6	4
Death	0	0
Hospitalization	0	0
Sinusitis	1	0
Otitis Media	3	3
Pneumonia	1	0
Bronchitis	1	0
Encephalitis/Encephalopathy	0	0
Febrile Seizures	0	1
Myositis	0	0

11. Secondary Outcome

Title	Percentage of Participants With Influenza-Related Complications
Description	Influenza related complications include death, hospitalization, radiologically confirmed pneumonia, bronchitis, sinusitis, otitis media, encephalitis/encephalopathy, febrile seizures, myositis.
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description

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/Group Title	Baloxavir Marboxil	Oseltamivir
Arm/Group Description	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.	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
Measure Participants	81	43
Total	7.4 6.4%	7.0 12.1%
Death	0 0%	0 0%
Hospitalization	0 0%	0 0%
Sinusitis	1.2 1%	0 0%
Otitis Media	3.7 3.2%	4.7 8.1%
Pneumonia	1.2 1%	0 0%
Bronchitis	1.2 1%	0 0%
Encephalitis/Encephalopathy	0 0%	0 0%
Febrile Seizures	0 0%	2.3 4%
Myositis	0 0%	0 0%

12. Secondary Outcome

Title	Percentage of Participants Requiring Antibiotics
Time Frame	Up to Day 29

Outcome Measure Data

Analysis Population Description

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/Group Title	Baloxavir Marboxil	Oseltamivir
Arm/Group Description	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.	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
Measure Participants	81	43
Total	4.9 4.3%	4.7 8.1%
Bronchitis	0 0%	0 0%
Otitis Media	2.5 2.2%	4.7 8.1%
Pneumonia	1.2 1%	0 0%
Sinusitis	1.2 1%	0 0%

13. Secondary Outcome

Title	Time to Cessation of Viral Shedding by Virus Titer
Description	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

Outcome Measure Data

Analysis Population Description

Includes all participants with post-baseline Virology assessment and a positive virus titer on Day 1

Arm/Group Title	Baloxavir Marboxil	Oseltamivir
Arm/Group Description	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.	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
Measure Participants	67	37
Median (95% Confidence Interval) [hours]	24.2	75.8

14. Secondary Outcome

Title	Time to Cessation of Viral Shedding by RT-PCR
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Baloxavir Marboxil	Oseltamivir
Arm/Group Description	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.	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
Measure Participants	76	39
Median (95% Confidence Interval) [hours]	242.5	238.9

15. Secondary Outcome

Title	Change From Baseline in Influenza Virus Titer at Day 2, 4, 6, 10, 15, 29
Description	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

Outcome Measure Data

Analysis Population Description

Includes all participants with a positive virus titer on Day 1

Arm/Group Title	Baloxavir Marboxil	Oseltamivir
Arm/Group Description	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.	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
Measure Participants	67	38
Baseline	4.43 (1.36)	4.27 (1.48)
Day 2	-3.59 (1.34)	-1.79 (1.54)
Day 3 (optional visit)	-2.83 (0.58)	-2.63 (0.88)
Day 4	-3.53 (1.38)	-3.27 (1.54)
Day 6	-3.55 (1.32)	-3.52 (1.50)
Day 10	-3.66 (1.40)	-3.50 (1.42)
Day 15 (optional visit)	-3.75 (0.54)	-3.63 (1.45)
Day 29	-3.50 (1.43)	-3.75 (1.19)

16. Secondary Outcome

Title	Change From Baseline in the Amount of Virus RNA (RT-PCR) at Day 2, 4, 6, 10, 15, 29
Description	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

Outcome Measure Data

Analysis Population Description

Includes all participants with positive virus RNA by RT-PCR on Day 1

Arm/Group Title	Baloxavir Marboxil	Oseltamivir
Arm/Group Description	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.	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
Measure Participants	76	40
Baseline	6.46 (1.50)	6.86 (1.02)
Day 2	-1.74 (1.13)	-1.12 (1.12)
Day 3 (optional)	-1.78 (1.50)	-2.21 (0.94)
Day 4	-2.40 (1.50)	-2.47 (1.35)
Day 6	-2.73 (1.78)	-3.32 (1.27)
Day 10	-3.55 (1.62)	-3.81 (1.19)
Day 15 (optional)	-1.24 (3.06)	-4.44 (NA)
Day 29	2.18 (NA)

17. Secondary Outcome

Title	Percentage of Participants With Positive Influenza Virus Titer at Day 2, 4, 6, 10
Time Frame	Baseline, Day 2, 3 (optional), 4, 6, 10

Outcome Measure Data

Analysis Population Description

Includes all participants with a positive virus titer on Day 1

Arm/Group Title	Baloxavir Marboxil	Oseltamivir
Arm/Group Description	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.	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
Measure Participants	67	38
Baseline	100 87%	100 172.4%
Day 2	15.6 13.6%	75.7 130.5%
Day 3 (optional)	33.3 29%	50.0 86.2%
Day 4	26.2 22.8%	29.0 50%
Day 6	12.7 11%	5.7 9.8%
Day 10	1.6 1.4%	0 0%

18. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Includes all participants with positive virus RNA by RT-PCR on Day 1

Arm/Group Title	Baloxavir Marboxil	Oseltamivir
Arm/Group Description	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.	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
Measure Participants	76	40
Baseline	100 87%	100 172.4%
Day 2	95.9 83.4%	100 172.4%
Day 3 (optional)	100 87%	100 172.4%
Day 4	89.9 78.2%	97.0 167.2%
Day 6	83.1 72.3%	75.7 130.5%
Day 10	46.5 40.4%	44.1 76%
Day 15 (optional)	40.0 34.8%	25.0 43.1%
Day 29	25.0 21.7%	0 0%

19. Secondary Outcome

Title	Area Under the Curve in Virus Titer
Description	Area under the curve (AUC) in virus titer was calculated using the trapezoidal method.
Time Frame	Day 1 - Day 29

Outcome Measure Data

Analysis Population Description

Includes all participants with post-baseline Virology assessment and a positive virus titer on Day 1

Arm/Group Title	Baloxavir Marboxil	Oseltamivir
Arm/Group Description	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.	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
Measure Participants	67	37
Mean (Standard Deviation) [log₁₀[TCID₅₀/mL]*hours]	-863.81 (543.37)	-849.29 (684.43)

20. Secondary Outcome

Title	Area Under the Curve in the Amount of Virus RNA (RT-PCR)
Description	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

Outcome Measure Data

Analysis Population Description

Includes all participants with positive virus RNA by RT-PCR on Day 1 and at least 1 post-baseline test.

Arm/Group Title	Baloxavir Marboxil	Oseltamivir
Arm/Group Description	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.	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
Measure Participants	75	39
Mean (Standard Deviation) [log₁₀ VPs/mL*hours]	-381.53 (338.53)	-353.31 (304.01)

21. Secondary Outcome

Title	Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of Baloxavir Marboxil
Description	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

Outcome Measure Data

Analysis Population Description

The PK population consists of all participants that have at least one post-dose drug concentration measurement at a scheduled visit time point

Arm/Group Title	Baloxavir Marboxil
Arm/Group Description	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.
Measure Participants	95
Non-Asian - 2 mg/kg	NA (NA)
Asian - 40 mg	NA (NA)
Non-Asian - 40 mg	NA (NA)

22. Secondary Outcome

Title	Area Under the Concentration to Time Curve From Time 0 to Infinity (AUC0-inf) of S-033447.
Description	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

Outcome Measure Data

Analysis Population Description

The PK population consists of all participants that have at least one post-dose drug concentration measurement at a scheduled visit time point

Arm/Group Title	Baloxavir Marboxil
Arm/Group Description	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.
Measure Participants	95
Non-Asian - 2 mg/kg	4050 (2080)
Asian - 40 mg	6600 (NA)
Non-Asian - 40 mg	4390 (2080)

23. Secondary Outcome

Title	Maximum Plasma Concentration (Cmax) of Baloxavir Marboxil
Description	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

Outcome Measure Data

Analysis Population Description

The PK population consists of all participants that have at least one post-dose drug concentration measurement at a scheduled visit time point

Arm/Group Title	Baloxavir Marboxil
Arm/Group Description	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.
Measure Participants	95
Non-Asian - 2 mg/kg	NA (NA)
Asian - 40 mg	NA (NA)
Non-Asian - 40 mg	NA (NA)

24. Secondary Outcome

Title	Maximum Plasma Concentration (Cmax) of S-033447
Description	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

Outcome Measure Data

Analysis Population Description

The PK population consists of all participants that have at least one post-dose drug concentration measurement at a scheduled visit time point

Arm/Group Title	Baloxavir Marboxil
Arm/Group Description	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.
Measure Participants	95
Non-Asian - 2 mg/kg	109 (55.3)
Asian - 40 mg	110 (NA)
Non-Asian - 40 mg	83.2 (36.5)

25. Secondary Outcome

Title	Time to Maximum Plasma Concentration (Tmax) of Baloxavir Marboxil
Description	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

Outcome Measure Data

Analysis Population Description

The PK population consists of all participants that have at least one post-dose drug concentration measurement at a scheduled visit time point

Arm/Group Title	Baloxavir Marboxil
Arm/Group Description	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.
Measure Participants	95
Non-Asian - 2 mg/kg	NA (NA)
Asian - 40 mg	NA (NA)
Non-Asian - 40 mg	NA (NA)

26. Secondary Outcome

Title	Time to Maximum Plasma Concentration (Tmax) of S-033447
Description	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

Outcome Measure Data

Analysis Population Description

The PK population consists of all participants that have at least one post-dose drug concentration measurement at a scheduled visit time point

Arm/Group Title	Baloxavir Marboxil
Arm/Group Description	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.
Measure Participants	95
Non-Asian - 2 mg/kg	4.12 (2.07)
Asian - 40 mg	5.50 (NA)
Non-Asian - 40 mg	5.55 (3.79)

27. Secondary Outcome

Title	Plasma Concentrations of Baloxavir Marboxil by Dosage
Description	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

Outcome Measure Data

Analysis Population Description

The PK population consists of all participants that have at least one post-dose drug concentration measurement at a scheduled visit time point

Arm/Group Title	Baloxavir Marboxil
Arm/Group Description	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.
Measure Participants	95
24 - Non-Asian - 2 mg/kg	NA (NA)
24 - Asian - 40 mg	NA (NA)
24 - Non-Asian - 40 mg	NA (NA)
72 - Non-Asian - 2 mg/kg	NA (NA)
72 - Asian - 40 mg	NA (NA)
72 - Non-Asian - 40 mg	NA (NA)
96 - Non-Asian - 2 mg/kg	NA (NA)
96 - Asian - 40 mg	NA (NA)
96 - Non-Asian - 40 mg	NA (NA)
240 - Non-Asian - 2 mg/kg	NA (NA)
240 - Asian - 40 mg	NA (NA)
240 - Non-Asian - 40 mg	NA (NA)

28. Secondary Outcome

Title	Plasma Concentrations of S-033447 by Dosage
Description	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

Outcome Measure Data

Analysis Population Description

The PK population consists of all participants that have at least one post-dose drug concentration measurement at a scheduled visit time point

Arm/Group Title	Baloxavir Marboxil
Arm/Group Description	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.
Measure Participants	95
24 - Non-Asian - 2 mg/kg	55.7 (28.1)
24 - Asian - 40 mg	75.2 (NA)
24 - Non-Asian - 40 mg	53.2 (22.4)
72 - Non-Asian - 2 mg/kg	13.2 (7.15)
72 - Asian - 40 mg	28.9 (NA)
72 - Non-Asian - 40 mg	17.90 (8.910)
96 - Non-Asian - 2 mg/kg	7.61 (4.400)
96 - Asian - 40 mg	19.0 (NA)
96 - Non-Asian - 40 mg	11.3 (6.160)
240 - Non-Asian - 2 mg/kg	0.989 (0.887)
240 - Asian - 40 mg	3.31 (NA)
240 - Non-Asian - 40 mg	1.85 (1.400)

Adverse Events

Time Frame	From baseline (Day 1) until 28 days after the last dose of study drug (29 days)
Arm/Group Title	Baloxavir Marboxil		Oseltamivir
Arm/Group Description	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.		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
All Cause Mortality
	Baloxavir Marboxil		Oseltamivir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/115 (0%)		0/58 (0%)
Serious Adverse Events
	Baloxavir Marboxil		Oseltamivir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/115 (0%)		0/58 (0%)
Other (Not Including Serious) Adverse Events
	Baloxavir Marboxil		Oseltamivir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/115 (13%)		13/58 (22.4%)
Gastrointestinal disorders
Diarrhoea	6/115 (5.2%)	6	1/58 (1.7%)	1
Vomiting	7/115 (6.1%)	7	9/58 (15.5%)	10
Infections and infestations
Otitis Media	3/115 (2.6%)	3	4/58 (6.9%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.