Study to Assess Efficacy and Safety of Baloxavir Marboxil In Combination With Standard-of-Care Neuraminidase Inhibitor In Hospitalized Participants With Severe Influenza

Influenza Clinical Trial

Official title:

A Phase III, Randomized, Double-Blind Placebo-Controlled, Multicenter Study To Evaluate the Efficacy and Safety of Baloxavir Marboxil in Combination With Standard-of-Care Neuraminidase Inhibitor in Hospitalized Participants With Severe Influenza

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03684044
• Other study ID #: CP40617
• Secondary ID: 2018-001416-30
• Status: Completed
• Phase: Phase 3
• Start date: January 8, 2019
• Est. completion date: March 16, 2020

Study information

• Verified date: December 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy, safety, and pharmacokinetics of baloxavir marboxil in combination with a standard-of-care (SOC) neuraminidase inhibitor (NAI) (i.e., oseltamivir, zanamivir, or peramivir) compared with a matching placebo in combination with a SOC NAI in hospitalized patients with influenza.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 363
• Est. completion date: March 16, 2020
• Est. primary completion date: March 16, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Adult participants: Signed informed consent by any participant capable of giving consent, or, where the participant is not capable of giving consent, by his or her legal/authorized representative
• Adolescent participants not able to legally consent: written informed consent for study participation is obtained from participant's parents or legal guardian, with assent as appropriate by the participant, depending on the participant's level of understanding and capability to provide assent
• Participants who require hospitalization for severe influenza or acquire influenza during hospitalization, the severity of which requires an extension of hospitalization
• Diagnosis of influenza A and/or B by a positive Rapid Influenza Diagnostic Test (RIDT) or reverse transcriptase-polymerase chain reaction (RT-PCR)
• The time interval between the onset of symptoms and randomization is within 96 hours
• A score of =4 based on the National Early Warning Score 2 (NEWS2)
• Participants will require objective criteria of seriousness defined by at least one of

the following criteria:

• Requires ventilation or supplemental oxygen to support respiration
• Has a complication related to influenza that requires hospitalization (e.g., pneumonia, central nervous system involvement, myositis, rhabdomyolysis, acute exacerbation of chronic kidney disease, asthma or chronic obstructive pulmonary disease (COPD), severe dehydration, myocarditis, pericarditis, exacerbation of ischemic heart disease)
• For women of childbearing potential: Agreement to remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 28 days after the last dose of study treatment. Hormonal contraceptive methods must be supplemented by a barrier method.

Exclusion Criteria:

• Participants who have received more than 48 hours of antiviral treatment for the current influenza infection prior to screening
• Participants who have received baloxavir marboxil for the current influenza infection
• Known contraindication to neuraminidase inhibitors
• Participants hospitalized for exclusively social reasons (e.g., lack of caregivers at home)
• Participants expected to die or be discharged within 48 hours, according to the investigator's judgement
• Participants weighing < 40 kg
• Participants with known severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2) or receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis
• Participants with any of the following laboratory abnormalities detected within 24

hours prior to or during screening (according to local laboratory reference ranges:

• Alanine Transaminase (ALT) or Aspartate Transaminase (AST) level > 5 times the upper limit of normal (ULN) OR
• ALT or AST > 3 times the ULN and total bilirubin level > 2 times the ULN
• Pregnant or breastfeeding, or positive pregnancy test in a predose examination, or intending to become pregnant during the study or within 28 days after the last dose of study treatment
• Exposure to an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization
• Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study
• Known hypersensitivity to baloxavir marboxil or the drug product excipients

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Drug:
• Baloxavir Marboxil
Baloxavir marboxil will be administered as a weight-based dose on Days 1 and 4. A third dose will be given on Day 7 for participants who have not improved according to protocol defined criteria on Day 5.

Other:
• Placebo
Participants will receive matching placebo on Days 1, 4 and 7.

Locations

Country	Name	City	State
Argentina	Instituto Medico Platense	La Plata
Australia	Royal Brisbane & Womens Hospital; Pharmacy Department	Herston	Queensland
Australia	Royal Children's Hospital Melbourne - PIN	Parkville	Victoria
Belgium	Cliniques Universitaires Saint-Luc; Hematology	Bruxelles
Belgium	Hopital Erasme; Chest Medicine, Cardiac & Thoracic Surgery	Bruxelles
Belgium	UZ Leuven	Leuven
Brazil	Santa Casa de Misericordia; de Belo Horizonte	Belo Horizonte	MG
Brazil	Centro de Estudos Clinicos do Interior Paulista	JAU	SP
Brazil	Hospital Sao Vicente de Paulo	Passo Fundo	RS
Bulgaria	Multiprofile Hospital For Active Treatment Sveta Ekaterina Dimitrovgrad EOOD; Internal Diseases	Dimitrovgrad
Bulgaria	Specialized Hospital for Active Treatment of Pneumophthisiatric Diseases - Haskovo EOOD	Haskovo
Bulgaria	MHAT Stamen Iliev AD; Pharmacy	Montana
Bulgaria	University Mulitiprofile Hospital for Active Treatment Sveti Georgi EAD; Pharmacy	Plovdiv
Bulgaria	Specialized Hospital for Active Treatment of Pneumophthisiatric Diseases Dr. D. Gramatikov - Ruse	Ruse
Bulgaria	Multiprofile Hospital for Active Treatment - Samokov EOOD	Samokov
Bulgaria	Multiprofile Hospital For Active Treatment Sliven ?? Military Hospital Sofia; Pharmacy	Sliven
Bulgaria	Multiprofile Hospital For Active Treatment - Dr. Bratan Shukerov AD; Pharmacy	Smolyan
Bulgaria	Fifth Multiprofile Hospital for Active Treatment - Sofia EAD; Pharmacy	Sofia
Bulgaria	First Multiprofile Hospital for Active Treatment - Sofia EAD	Sofia
Bulgaria	Military Medical Academy Multiprofile Hospital for Active Treatment - Sofia; Pharmacy	Sofia
Bulgaria	National Multiprofile Transport Hospital Tzar Boris Ill; Clinic of Internal Diseases	Sofia
Bulgaria	Multiprofile District Hospital for Active Treatment Dr. Stefan Cherkezov AD; Pharmacy	Veliko Tarnovo
Bulgaria	Specialized Hospital for Active Treatment of Pneumophthisiatric Diseases-Vratsa; Pharmacy	Vratsa
Canada	Carlson Urology	Calgary	Alberta
Canada	Foothills Medical Centre	Calgary	Alberta
Canada	Peter Lougheed Centre	Calgary	Alberta
Canada	South Health Campus	Calgary	Alberta
Canada	Toronto East General Hospital; Main Pharmacy G Wing Basement	East York	Ontario
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	London Health Sciences Center; Pharmacy Dept.	London	Ontario
Canada	Institut Universitaire de Cardiologie et de Pneumologie	Quebec
China	Beijing Ditan Hospital Capital Medical University	Beijing
China	China-Japan Friendship Hospital	Beijing
China	Beijing Youan Hospital, Capital Medical University; Center for Infectious Diseases	Beijing City
China	West China Hospital, Sichuan University	Chengdu
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou
China	The First Affiliated Hospital of College of Medicine, Zhejiang University	Hangzhou
China	The 1st Affiliated Hospital of Nanchang Unversity	Nanchang
China	Shanghai Jiao Tong University School of Medicine (SJTUSM) - Ruijin Hospital (GuangCi Hospital)	Shanghai
China	Shanghai Public Health Clinical Center	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai
Czechia	Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika	Brno
Czechia	Nemocnice Kyjov, prispevkova organizace	Kyjov
Estonia	East Tallinn Central Hospital	Tallinn
Finland	Kuopion Yliopistollinen Sairaala; Silmätaudit	Kuopio
Finland	Oulun Yliopistollinen Sairaala; Teho-osasto	Oulu
Finland	Turku University Hospital	Turku
France	Centre Hospitalier Victor Dupouy	Argenteuil
France	CHRU Dijon Complexe Du Bocage	Dijon
France	Centre Hospitalier Departemental de Vendee	La Roche Sur Yon
France	Hôpital Universitaire Dupuytren	Limoges
France	CHRU Nantes	Nantes
France	CHU de Nîmes - Hôpital Carémeau	Nimes
France	Hopital de La Source	Orleans
France	Groupe Hospitalier Pitie Salpetriere; Service De Pneumologie	Paris
France	Nouvel Hopital Civil - CHU Strasbourg	Strasbourg
France	CHRU Bretonneau	Tours
Germany	Krankenhaus Donaustauf der LVA Niederbayern Oberpfalz	Donaustauf
Germany	Universitätsklinikum Carl Gustav Carus an der TU Dresden	Dresden
Germany	St. Josefskrankenhaus - Freiburg; Klinik fur Pneumologieund Beatmungsmedizin	Freiburg im Breisgau
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Uniklinik Koln; Klinik I fur Innere Medizin	Köln
Germany	Universitatsklinikum Schleswig-Holstein; Klinik fuer Innere Medizin I	Lubeck
Germany	Klinikum Mannheim GmbH Universitätsklinikum	Mannheim
Germany	Klinikum der Universität Regensburg	Regensburg
Germany	Universitatsklinikum Tubingen	Tübingen
Hong Kong	Princess Margaret Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Prince of Wales Hospital	Shatin, New Territories
Israel	Soroka University Medical Centre	Beer Sheva
Israel	Edith Wolfson Medical Center	Holon
Israel	Galilee Medical Center	Nahariya
Israel	Chaim Sheba Medical Center; Allergy and Clinical Immunology Unit	Ramat Gan
Israel	Rambam Health Corporation; Oncology Institute	Rambam
Israel	ZIV Medical Center; Department Of Internal Medicine A	Safed
Israel	Tel Aviv Sourasky Medical Center; Pharmacy	Tel Aviv
Israel	Baruch Padeh Poria Medical Center; Pharmacy	Tiberias
Japan	Fujita General Hospital	Dategun Kunimimachi
Japan	Fukuoka Shin Mizumaki Hospital	Fukuoka
Japan	Fukuoka Wajiro Hospital	Fukuoka
Japan	Shin Komonji Hospital	Fukuoka
Japan	Rinku General Medical Center	Izumisano
Japan	National Hospital Organization Minami Kyoto Hospital	Joyo
Japan	National Hospital Organization Kanazawa Medical Center	Kanazawa
Japan	Japanese Red Cross Kumamoto Hospital	Kumamoto-shi
Japan	Naha City Hospital	Naha
Japan	National Hospital Organization Ibarakihigashi National Hospital; Center for Clinical Research	Naka-gun
Japan	Japan Community Health care Organization Nihonmatsu hospital	Nihonmatsu
Japan	Social Corporation Keigakukai Minamiosaka Hosupital	Osaka
Japan	National Hospital Organaization Shibukawa Medical Center	Shibukawa
Japan	Tokyo Shinagawa Hospital Medical Corporation Association Tokyokyojuno-kai	Shinagawa
Japan	Saka General Hospital	Shiogama
Japan	Local incorporated administrative agency Shizuoka City Shizuoka Hospital	Shizuoka
Japan	Iwase General Hospital	Sukagawa
Japan	Center Hospital of the National Center for Global Health and Medicine	Tokyo
Japan	Nagata Hospital; Department of pulmonary medicine	Yanagawa-shi
Korea, Republic of	The Catholic University of Korea Incheon St. Mary's Hospital	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	ChungAng University Hospital	Seoul
Korea, Republic of	Hallym University Kangnam Sacred Heart Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Mexico	Hospital Civil Fray Antonio Alcalde; Instituto de Patologia Infecciosa	Guadalajara
Mexico	Instituto Nacional de Ciencias Médicas y Nutricion Dr. Salvador Zubiran; Hamatologia y Oncologia	Mexico	Mexico CITY (federal District)
Mexico	Hospital Universitario Dr. Jose Eleuterio González; Enfermedades Pulmonares Crónicas	Monterrey
Mexico	Hospital General de Tijuana	Tijuana
Netherlands	Leids Universitair Medisch Centrum; C5-P Stafcentrum Hartziekten	Leiden
Netherlands	Canisius Wilhelmina Ziekenhuis; Department Hematology	Nijmegen
Netherlands	Ikazia Ziekenhuis	Rotterdam
Netherlands	Zuyderland Medisch Centrum - Sittard Geleen	Sittard-Geleen
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
New Zealand	Wellington Hospital	Wellington
Peru	Hospital Alberto Sabogal Sologuren	Callao
Peru	Hospital Nacional Adolfo Guevara Velasco - ESSALUD; Servicio de Cardiología	Cusco
Romania	Dr. Victor Babes Clinical Hospital For Tropical and Infectious Diseases	Bucharest
Romania	Prof. Dr. Matei Bals Institute of Infectious Diseases	Bucharest
Romania	Spitalul Clinic de Boli Infectioase	Cluj Napoca
Romania	Sf.Cuv. Parascheva Infectious Diseases Clinical Hospital	Galati
Romania	Spitalul Clinic de Boli Infectioase "Sfanta Parascheva" Iasi	Iasi
Romania	Sibiu Emergency Clinical County Hospital	Sibiu
Romania	Sf. Ioan cel Nou Emergency County Hospital	Suceava
Serbia	Clinical Center of Serbia	Belgrade
Serbia	Clinical Hospital Center Zvezdara	Belgrade
Serbia	Clinical Center Kragujevac	Kragujevac
Serbia	Clinical Center Nis; Clinic for Pulmonary Diseases and Tuberculosis Knez Selo	Nis
Serbia	Clinical Centre of Vojvodina	Nova Sad
Serbia	General Hospital Dr Radivoj Simonovic Sombor	Sombor
Serbia	Institute of Lung Diseases Vojvodina	Sremska Kamenica
Singapore	Tan Tock Seng Hospital	Singapore
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Universitario Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario Vall d'Hebron - PPDS	Barcelona
Spain	Hospital Sant Joan de Deu - PIN; Unitat de Recerca - Farmacia	Esplugues de Llobregat	Barcelona
Spain	Hospital Universitario Fundacion Jimenez Diaz.	Madrid
Spain	Hospital General Universitario Reina Sofia; Servicio de Nefrologia	Murcia
Spain	Hospital Universitario Marques de Valdecilla	Santander	Cantabria
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Mutua de Terrassa	Terrassa	Barcelona
Spain	Hospital Universitario de Torrejon	Torrejon de Ardoz	Madrid
Spain	Hospital de La Ribera	Valencia
Sweden	Sahlgrenska Universitetssjukhuset	Goteborg
Sweden	Skånes Universitetssjukhus Malmö; Infektionskliniken	Malmö
Turkey	Hacettepe University Medical Faculty	Ankara
Turkey	Akdeniz University Medical Faculty	Antalya
Turkey	Selcuk University Medical Faculty; Internal Medicine	Konya
Turkey	Karadeniz Technical University Faculty of Medicine	Trabzon
Ukraine	Regional Municipal Institution Chernivtsi Regional Clinical Hospital	Chernivtsi	Chernihiv Governorate
Ukraine	MI Dnipropetrovsk City Clinical Hospital #21 n.a. Prof. Popkova of DRC; The First Department	Dnipro	Podolia Governorate
Ukraine	Kyiv Oleksandrivska Clinical Hospital; Infectious Box Department #2	Kyiv	Katerynoslav Governorate
Ukraine	Municipal Institution City Clinical Infectious Diseases Hospital	Odesa
Ukraine	Regional Municipal Institution Sumy Regional Infectious Clinical Hospital n.a. Z.Y. Krasovytskyi	Sumy	Katerynoslav Governorate
Ukraine	Ternopil City Municipal Emergency Hospital; Infectious Department	Ternopil	KIEV Governorate
Ukraine	Communal Non-Commercial Enterprise "Vinnytsia City Clinical Hospital ?1"; Infectious Department	Vinnytsia	KIEV Governorate
Ukraine	MI Vinnytsia Regional Clinical Children's Infectious Hospital; Infectiuos Box department	Vinnytsia	KIEV Governorate
United States	New York-Presbyterian Brooklyn Methodist Hospital; Department of Emergency Medicine	Brooklyn	New York
United States	Mercury Street Medical Group	Butte	Montana
United States	University of Chicago; Oncology Dept	Chicago	Illinois
United States	Atlanta Institute For Medical Research, Inc; DeKalb Medical Pharmacy	Decatur	Georgia
United States	Denver Health Medical Center	Denver	Colorado
United States	Detroit Receiving Hospital	Detroit	Michigan
United States	NorthShore University HealthSystem	Evanston	Illinois
United States	Froedtert and The Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Barnum Medical Research, Inc.	Natchitoches	Louisiana
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Temple University Hospital ; Lung Center	Philadelphia	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Salem Veterans Affairs Medical Center - NAVREF; Pharmacy	Salem	Virginia
United States	Torrance Memorial Medical Center	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  Czechia,  Estonia,  Finland,  France,  Germany,  Hong Kong,  Israel,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  New Zealand,  Peru,  Romania,  Serbia,  Singapore,  Spain,  Sweden,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Clinical Improvement	Time to Clinical Improvement (TTCI) is defined as Time to Hospital Discharge OR Time to NEWS2 (National Early Warning Score 2) of = 2 maintained for 24 hours.	Up to Day 35
Secondary	Response Rates of the 6-Point Ordinal Scale at Day 7	The ordinal scale categories are: Category 1) Discharged (or "ready for discharge") Category 2) Non-ICU hospital ward (or "ready for hospital ward") not requiring supplemental oxygen/non-invasive ventilation Category 3) Non-ICU hospital ward (or "ready for hospital ward") requiring supplemental oxygen/non-invasive ventilation Category 4) ICU without mechanical (invasive) ventilation (or "ready for ICU admission") Category 5) Mechanical (invasive) ventilation Category 6) Death	Day 7
Secondary	Time to Clinical Response	Time to Clinical Response is based on temperature ranges, oxygen saturation, respiratory status, heart rate, and hospitalization status.	Up to Day 35
Secondary	Percentage of Participants on Mechanical Ventilation		Up to Day 35
Secondary	Duration of Mechanical Ventilation		Up to Day 35
Secondary	Percentage of Participants Requiring ICU Stay		Up to Day 35
Secondary	Duration of ICU Stay		Up to Day 35
Secondary	Time to Clinical Failure	Time to clinical failure, defined as the time to death, mechanical ventilation, or ICU admission, corresponding to ordinal scale categories 6, 5, and 4, respectively, from baseline	Up to Day 35
Secondary	Time to Hospital Discharge		Up to Day 35
Secondary	Percentage of Participants With Post-Treatment Influenza-Related Complications	Influenza-related complications included pneumonia, myositis or rhabdomyolysis, encephalitis or encephalopathy, myocarditis and/or pericarditis, otitis media, sinusitis, exacerbation of COPD/asthma, sepsis, acute lung injury or acute respiratory distress syndrome.	Up to Day 35
Secondary	Mortality Rate at Day 7		Up to Day 7
Secondary	Mortality Rate at Day 28		Up to Day 28
Secondary	Time to NEWS2 of = 2 Maintained for 24 Hours	A score of 0 (Range 0 - 3) indicates normal health conditions.	Up to Day 35
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 study treatment and first time when the influenza virus titer is below the limit of detection (0.75 log10 TCID50/mL)	Screening (baseline) and on Days 2, 3, 4, 5, 7, and 10
Secondary	Change From Baseline in Influenza Virus Titer at Each Timepoint	Influenza virus titer 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.	Days 2, 3, 4, 5, 7, and 10
Secondary	Percentage of Participants With Positive Influenza Virus Titer at Each Timepoint	Influenza virus titer 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 (log10 TCID50/mL). A lower value indicates lower viral titer.	Days 2, 3, 4, 5, 7, and 10
Secondary	Area Under the Curve in Virus Titer		Days 1, 2, 3, 4, 5, 7, and 10
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 study treatment and first time when the virus RNA by RT-PCR is below the limit of detection (2.05 for flu A and 2.83 for flu B log10 virus particles/mL)	Screening (baseline) and on Days 2, 3, 4, 5, 7, and 10
Secondary	Change From Baseline in the Amount of Virus RNA (RT-PCR) at Each Timepoint	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)	Days 2, 3, 4, 5, 7, and 10
Secondary	Percentage of Participants Positive by RT-PCR at Each Timepoint	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)	Days 2, 3, 4, 5, 7, and 10
Secondary	Area Under the Curve in the Amount of Virus RNA (RT-PCR)		Days 1, 2, 3, 4, 5, 7, and 10
Secondary	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.	Up to Day 35
Secondary	Percentage of Participants With AEs and SAEs Leading to Discontinuation From Treatment	Discontinuation from study treatment.	Up to Day 35
Secondary	Percentage of Participants With Any Post-Treatment ALT and AST Above Baseline and >3 × ULN, >5 × ULN, >10 × ULN	ALT = alanine aminotransferase AST = aspartate transaminase	Up to Day 35
Secondary	Plasma Concentration of Baloxavir (Active Metabolite) at Specified Time Points		Day 1, 2, 4, 5, 7 and 8
Secondary	Area Under the Concentration to Time Curve From Time 0 to 72 Hours (AUC0-72) of Baloxavir		0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8
Secondary	Maximum Plasma Concentration (Cmax) of Baloxavir		0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8
Secondary	Apparent Half-Life (T1/2) of Baloxavir		0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8
Secondary	Concentration at 24 Hours (C24) of Baloxavir		0, 0.5, 2, 4, 10, 24, 72 hours from dose on Day 1 and on Day 4, and Day 7, Day 8