Influenza
Conditions
Keywords
Flu, Baloxavir Marboxil, Oseltamivir, Tamiflu®
Brief summary
The primary objective of this study is to evaluate the efficacy of a single, oral dose of baloxavir marboxil compared with placebo by measuring the time to alleviation of symptoms in patients with uncomplicated influenza virus infection.
Interventions
2 to4 X 20-mg tablets taken orally
2 to4 X 20-mg tablets taken orally
DRUGOseltamivir
75 mg capsules taken orally
Placebo capsules matching oseltamivir 75 mg capsules
Sponsors
Shionogi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
1. Patients who are able to understand the study and comply with all study procedures, and willing to provide written informed consent/assent prior to the predose examinations appropriately. As for adolescent patients, informed consent/assent of voluntary participation should be obtained in accordance with local requirements 2. Male or female patients aged ≥ 12 to ≤ 64 years at the time of signing the informed consent/assent form. 3. Patients with a diagnosis of influenza virus infection confirmed by all of the following: 1. Fever ≥ 38ºC (axillary) in the predose examinations or \> 4 hours after dosing of antipyretics if they were taken 2. At least one of the following general systemic symptoms associated with influenza are present with a severity of moderate or greater * Headache * Feverishness or chills * Muscle or joint pain * Fatigue 3. At least one of the following respiratory symptoms associated with influenza are present with a severity of moderate or greater * Cough * Sore throat * Nasal congestion 4. The time interval between the onset of symptoms and the predose examinations is 48 hours or less. The onset of symptoms is defined as either: 1. Time of the first increase in body temperature (an increase of at least 1ºC from normal body temperature) 2. Time when the patient experiences at least one general or respiratory symptom 5. Women of childbearing potential who agree to use a highly effective method of contraception for 3 months after the first dose of study drug
Exclusion criteria
1. Patients with severe influenza virus infection requiring inpatient treatment. 2. Patients aged ≥ 20 years with known allergy to oseltamivir (Tamiflu®). 3. Patients with any of the following risk factors 1. Women who are pregnant or within 2 weeks post-partum 2. Residents of long-term care facilities (eg, welfare facilities for the elderly, nursing homes) 3. Chronic respiratory diseases including bronchial asthma 4. Neurological and neurodevelopmental disorders including disorders of the brain, spinal cord, peripheral nerve, and muscle (eg, cerebral palsy, epilepsy \[seizure disorders\], stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury) 5. Heart disease (such as congenital heart disease, congestive heart failure, or coronary artery disease), excluding hypertension without any other heart-related symptoms) 6. American Indians and Alaskan natives 7. Blood disorders (such as sickle cell disease) 8. Endocrine disorders (including diabetes mellitus) 9. Kidney disorders 10. Liver disorders 11. Metabolic disorders 12. Compromised immune system (including patients receiving immunosuppressant therapy, or those with cancer or human immunodeficiency virus \[HIV\] infection) 13. Morbid obesity (body mass index \[BMI\] ≥ 40) 4. Patients unable to swallow tablets or capsules. 5. Patients who have previously received Baloxavir Marboxil. 6. Patients weighing \< 40 kg 7. Patients who have been exposed to an investigational drug within 30 days prior to the predose examinations. 8. Women who are breastfeeding or have a positive pregnancy test in the predose examinations. The following female patients who have documentation of either a or b below do not need to undergo a pregnancy test in the predose examinations: 1. Postmenopausal (defined as cessation of regular menstrual periods for 2 years or more and confirmed by a follicle-stimulating hormone test) women 2. Women who are surgically sterile by hysterectomy, bilateral oophorectomy, or tubal ligation 9. Patients with concurrent infections requiring systemic antimicrobial and/or antiviral therapy at the predose examinations. 10. Patients who have received peramivir, laninamivir, oseltamivir, zanamivir, rimantadine, umifenovir, or amantadine within 30 days prior to the predose examinations. 11. Patients who have received an investigational monoclonal antibody for a viral disease in the last year. 12. Patients with severe underlying diseases. 13. Patients with known creatinine clearance ≤ 60 mL/min. 14. Patients who, in the opinion of the investigator, would be unlikely to comply with required study visits, self-assessments, and interventions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Alleviation of Symptoms in Participants Randomized to Baloxavir or Placebo | Initiation of study treatment up to Day 14 | Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of symptoms was defined as the time from the start of the study treatment to the time when all seven influenza-related symptoms were assessed by the participant as absent (0) or mild (1) for at least 21.5 hours. Time to alleviation of symptoms was analyzed using the Kaplan-Meier (KM) method; participants who did not experience alleviation of symptoms were censored at the last observation time point. |
| Time to Alleviation of Symptoms in Adults Randomized to Baloxavir or Oseltamivir | Initiation of study treatment up to Day 14 | Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of symptoms was defined as the time from the start of the study treatment to the time when all seven influenza-related symptoms were assessed by the participant as absent (0) or mild (1) for at least 21.5 hours. Time to alleviation of symptoms was analyzed using the Kaplan-Meier(KM) method; participants who did not experience alleviation of symptoms were censored at the last observation time point. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo | Days 2, 3, 4 (optional), 5, 6 (optional), and 9 | Influenza virus ribonucleic acid (RNA) was quantified from nasopharyngeal swabs (or throat swabs, if nasopharyngeal swabbing was not feasible). The percentage of participants with detectable virus RNA (2.05 for flu A and 2.83 for flu B log₁₀ virus particles/mL) among those assessed measured by reverse transcription polymerase chain reaction (RT-PCR) on Days 2, 3, 4, 5, 6 and 9. |
| Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Days 2, 3, 4 (optional), 5, 6 (optional), and 9 | Influenza virus RNA was quantified from nasopharyngeal swabs (or throat swabs, if nasopharyngeal swabbing was not feasible). The percentage of participants with detectable virus RNA (2.05 for flu A and 2.83 for flu B log₁₀ virus particles/mL) among those assessed measured by reverse transcription polymerase chain reaction (RT-PCR) on Days 2, 3, 4, 5, 6 and 9. |
| Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9 | Virus titer was quantified from nasopharyngeal swabs (or throat swabs if nasopharyngeal swabbing was not feasible) by tissue culture methods. If virus titer was less than the lower limit of quantification, the virus titer was imputed 0.7 (TCID₅₀/mL). |
| Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9 | Virus titer was quantified from nasopharyngeal swabs (or throat swabs if nasopharyngeal swabbing was not feasible) by tissue culture methods. If virus titer was less than the lower limit of quantification, the virus titer was imputed 0.7 (TCID₅₀/mL). |
| Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9 | Nasopharyngeal swabs (or throat swabs, if nasopharyngeal swabbing was not feasible) were obtained for viral quantitation. Virus RNA is measured by reverse transcription polymerase chain reaction (RT-PCR). |
| Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9 | Nasopharyngeal swabs (or throat swabs, if nasopharyngeal swabbing was not feasible) were obtained for viral quantitation. Virus RNA was measured by reverse transcription polymerase chain reaction (RT-PCR). |
| Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Participants Randomized to Baloxavir or Placebo | Day 1 to Day 9 | This endpoint was defined as AUC of change from Baseline in virus titer from Day 1 to Day 9. AUC was calculated using the trapezoidal method. |
| Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Adults Randomized to Baloxavir or Oseltamivir | Day 1 to Day 9 | This endpoint was defined as AUC of change from Baseline in virus titer from Day 1 to Day 9. AUC was calculated using the trapezoidal method. |
| Area Under the Curve (AUC) Adjusted by Baseline of Influenza Virus RNA in Participants Randomized to Baloxavir or Placebo | Day 1 to Day 9 | This endpoint was defined as AUC of change from baseline in the amount of virus RNA (RT-PCR) from Day 1 to Day 9. The AUC was calculated using the trapezoidal method. |
| Area Under the Curve (AUC) Adjusted by Baseline of Influenza Virus RNA in Adults Randomized to Baloxavir or Oseltamivir | Day 1 to Day 9 | This endpoint was defined as AUC of change from baseline in the amount of virus RNA (RT-PCR) from Day 1 to Day 9. The AUC was calculated using the trapezoidal method. |
| Time to Cessation of Viral Shedding Determined by Virus Titer in Participants Randomized to Baloxavir or Placebo | Day 1 to Day 9 | Time to cessation of viral shedding by virus titer was defined as the time between the initiation of the study treatment and first time when the virus titer was below the limit of detection (0.7 log₁₀\[TCID₅₀/mL\]). The median and 95% confidence interval (CI) for time to cessation of viral shedding determined by virus titer was analyzed using the Kaplan-Meier (KM) method; participants whose virus titer had not reached cessation by the last observation time point were treated as censored at that time point. |
| Time to Cessation of Viral Shedding Determined by Virus Titer in Adults Randomized to Baloxavir or Oseltamivir | Day 1 to Day 9 | Time to cessation of viral shedding by virus titer was defined as the time between the initiation of the study treatment and first time when the virus titer was below the limit of detection (0.7 log₁₀\[TCID₅₀/mL\]). The time to cessation of viral shedding determined by virus titer was analyzed using the Kaplan-Meier (KM) method; participants whose virus titer had not reached cessation by the last observation time point were treated as censored at that time point. |
| Time to Cessation of Viral Shedding Determined by Virus RNA in Participants Randomized to Baloxavir or Placebo | Day 1 to Day 9 | Time to cessation of viral shedding by RT-PCR was defined as the time between the initiation of the study treatment and first time when the virus RNA was below the limit of detection measured by RT-PCR. Time to cessation of viral shedding by RT-PCR was analyzed using the KM method; participants whose virus RNA had not reached cessation by the last observation time point were treated as censored at that time point. |
| Time to Cessation of Viral Shedding Determined by Virus RNA in Adults Randomized to Baloxavir or Oseltamivir | Day 1 to Day 9 | Time to cessation of viral shedding by RT-PCR was defined as the time between the initiation of the study treatment and first time when the virus RNA was below the limit of detection measured by RT-PCR. Time to cessation of viral shedding by RT-PCR was analyzed using the KM method; participants whose virus RNA had not reached cessation by the last observation time point were treated as censored at that time point. |
| Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 12, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours after the initial dose of study treatment | Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Alleviation of symptoms was defined as all seven influenza-related symptoms assessed by the participant as absent (0) or mild (1) . |
| Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 12, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours after the initial dose of study treatment | Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Alleviation of symptoms was defined as all seven influenza-related symptoms assessed by the participant as absent (0) or mild (1) . |
| Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 12, 24, 36, 48, 72, 96 and 120 hours after the initial dose of study treatment | Participant's self-measured axillary temperature using an electronic thermometer. |
| Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Days 2, 3, 4 (optional), 5, 6 (optional), and 9 | Virus titer was quantified from nasopharyngeal swabs (or throat swabs if nasopharyngeal swabbing was not feasible) by tissue culture methods. Positive influenza virus titer was defined as virus titer not less than the lower limit of quantification (0.7 log₁₀ of the 50% tissue culture infective dose (TCID₅₀/mL) among those assessed for virus titer on Days 2, 3, 4, 5, 6 and 9. |
| Time to Alleviation of the Four Systemic Symptoms in Adults Randomized to Baloxavir or Oseltamivir | Initiation of study treatment up to Day 14 | Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of the 4 systemic symptoms was defined as the time between the initiation of the study treatment to the time when all 4 systemic symptoms (headache, feverishness or chills, muscle or joint pain, and fatigue) were assessed by the participant as 0 (None) or 1 (Mild) for a duration of at least 21.5 hours. Time to alleviation of the 4 systemic symptoms was analyzed using KM methods; participants who did not experience alleviation of symptoms were censored at the last observation time point. |
| Time to Alleviation of the Three Respiratory Symptoms in Participants Randomized to Baloxavir or Placebo | Initiation of study treatment up to Day 14 | Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of the 3 respiratory symptoms was defined as the time from the start of study treatment to the time when all 3 respiratory symptoms (cough, sore throat and nasal congestion) were assessed by the participant as absent (0) or mild (1) for at least 21.5 hours. Time to alleviation of the 3 respiratory symptoms was analyzed using the KM method; participants who did not experience alleviation of symptoms were censored at the last observation time point. |
| Time to Alleviation of the Three Respiratory Symptoms in Adults Randomized to Baloxavir or Oseltamivir | Initiation of study treatment up to Day 14 | Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of the 3 respiratory symptoms was defined as the time from the start of study treatment to the time when all 3 respiratory symptoms (cough, sore throat and nasal congestion) were assessed by the participant as absent (0) or mild (1) for at least 21.5 hours. Time to alleviation of the 3 respiratory symptoms was analyzed using the KM method; participants who did not experience alleviation of symptoms were censored at the last observation time point. |
| Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 1 pretreatment (Baseline) and 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, and 216 hours after the initial dose of study treatment. | Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). The composite symptom score is the total score of the 7 influenza symptoms as assessed by the participant, and ranges from 0 to 21. |
| Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 1 pretreatment (Baseline) and 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, and 216 hours after the initial dose of study treatment. | Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). The composite symptom score is the total score of the 7 influenza symptoms as assessed by the participant, and ranges from 0 to 21. |
| Time to Resolution of Fever in Participants Randomized to Baloxavir or Placebo | Initiation of study treatment up to Day 14 | Time to resolution of fever was defined as the time between the initiation of the study treatment and the resolution of fever. The resolution of fever was defined as the time when the participant's self-measured axillary temperature became less than 37ºC and was maintained at less than 37ºC for a duration of at least 12 hours. Time to resolution of fever was analyzed using KM methods; participants who did not experience resolution of fever by the last observation time point were censored at that time point. |
| Time to Resolution of Fever in Adults Randomized to Baloxavir or Oseltamivir | Initiation of study treatment up to Day 14 | Time to resolution of fever was defined as the time between the initiation of the study treatment and the resolution of fever. The resolution of fever was defined as the time when the participant's self-measured axillary temperature became less than 37ºC and was maintained at less than 37ºC for a duration of at least 12 hours. Time to resolution of fever was analyzed using KM methods; participants who did not experience resolution of fever by the last observation time point were censored at that time point. |
| Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 12, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours after the initial dose of study treatment | Defined as the percentage of patients whose axillary temperature dropped to less than 37ºC after the initiation of study treatment. |
| Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 12, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours after the initial dose of study treatment | Defined as the percentage of patients whose axillary temperature dropped to less than 37ºC after the initiation of study treatment. |
| Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 12, 24, 36, 48, 72, 96 and 120 hours after the initial dose of study treatment | Participant's self-measured axillary temperature using an electronic thermometer. |
| Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo | Initiation of study treatment up to Day 14 | Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of each symptom was defined as the time from the start of treatment to the start of the time period when the individual symptom was assessed by the participant as 0 (None) or 1 (Mild) for a duration of at least 21.5 hours. |
| Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir | Initiation of study treatment up to Day 14 | Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of each symptom was defined as the time from the start of treatment to the start of the time period when the individual symptom was assessed by the participant as 0 (None) or 1 (Mild) for a duration of at least 21.5 hours. |
| Time to Return to Preinfluenza Health Status in Participants Randomized to Baloxavir or Placebo | Initiation of study treatment up to Day 14 | Participants were asked to record their preinfluenza health status on a scale from 0 (worst possible health) to 10 (normal health \[for someone your age and your health condition\]), and their health status every day after initiation of study treatment on the same scale. Return to preinfluenza health status was defined as time from the initiation of the study treatment to the first time when the health status score was equal to or higher than the preinfluenza health status score. Time to return to preinfluenza health status was analyzed using KM methods; participants with a smaller number on the scale for health status by the last observation time point were censored at that time point. |
| Time to Return to Preinfluenza Health Status in Adults Randomized to Baloxavir or Oseltamivir | Initiation of study treatment up to Day 14 | Participants were asked to record their preinfluenza health status on a scale from 0 (worst possible health) to 10 (normal health \[for someone your age and your health condition\]), and their health status every day after initiation of study treatment on the same scale. Return to preinfluenza health status was defined as time from the initiation of the study treatment to the first time when the health status score was equal to or higher than the preinfluenza health status score. Time to return to preinfluenza health status was analyzed using KM methods; participants with a smaller number on the scale for health status by the last observation time point were censored at that time point. |
| Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo | Initiation of study treatment up to Day 14 | The percentage of participants who experienced each influenza-related complication (hospitalization, death, sinusitis, otitis media, bronchitis, and radiologically confirmed pneumonia) as an adverse event after the initiation of the study treatment. |
| Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir | Initiation of study treatment up to Day 14 | The percentage of participants who experienced each influenza-related complication (hospitalization, death, sinusitis, otitis media, bronchitis, and radiologically confirmed pneumonia) as an adverse event after the initiation of the study treatment. |
| Percentage of Participants With Adverse Events (AEs) | From first dose of study drug to Day 22 | — |
| Time to Alleviation of the Four Systemic Symptoms in Participants Randomized to Baloxavir or Placebo | Initiation of study treatment up to Day 14 | Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of the 4 systemic symptoms was defined as the time between the initiation of the study treatment to the time when all 4 systemic symptoms (headache, feverishness or chills, muscle or joint pain, and fatigue) were assessed by the participant as 0 (None) or 1 (Mild) for a duration of at least 21.5 hours. Time to alleviation of the 4 systemic symptoms was analyzed using KM methods; participants who did not experience alleviation of symptoms were censored at the last observation time point. |
| Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Days 2, 3, 4 (optional), 5, 6 (optional), and 9 | Virus titer was quantified from nasopharyngeal swabs (or throat swabs if nasopharyngeal swabbing was not feasible) by tissue culture methods. Positive influenza virus titer was defined as virus titer not less than the lower limit of quantification (0.7 log₁₀ of the 50% tissue culture infective dose (TCID₅₀/mL) among those assessed for virus titer on Days 2, 3, 4, 5, 6 and 9. |
Participant flow
Recruitment details
This study was conducted at 297 sites, consisting of 141 sites in Japan, 149 sites in the United States, and 7 sites in Canada. Participants were enrolled from December 2016 to April 2017.
Pre-assignment details
Participants 20 to 64 years of age were randomly assigned in a 2:2:1 ratio to receive a single oral dose of baloxavir, 75 mg oseltamivir twice daily for 5 days, or matching placebos. Participants 12 to 19 years of age were randomly assigned in a 2:1 ratio to receive a single dose of either baloxavir or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Baloxavir Participants aged 20 to 64 years received 40 mg or 80 mg baloxavir (depending on weight) orally on Day 1 and placebo to oseltamivir orally twice a day (BID) on Days 1 to 5.
Participants aged 12 to 19 years received 40 mg or 80 mg baloxavir (depending on weight) on Day 1. | 456 |
| Placebo Participants aged 20 to 64 years received placebo to baloxavir on Day 1 and placebo to oseltamivir orally twice a day on Days 1 to 5. Participants aged 12 to 19 years received placebo to baloxavir on Day 1. | 231 |
| Oseltamivir Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. | 377 |
| Total | 1,064 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 4 |
| Overall Study | Failure to Meet Eligibility Criteria | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 2 | 0 |
| Overall Study | Lost to Follow-up | 12 | 5 | 0 |
| Overall Study | Miscellaneous | 2 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 17 | 9 | 11 |
Baseline characteristics
| Characteristic | Placebo | Oseltamivir | Baloxavir | Total |
|---|---|---|---|---|
| Age, Continuous | 33.9 Years STANDARD_DEVIATION 13.7 | 36.0 Years STANDARD_DEVIATION 11.8 | 33.5 Years STANDARD_DEVIATION 13.5 | 34.5 Years STANDARD_DEVIATION 13 |
| Age, Customized ≥ 12 to ≤ 19 years | 38 Participants | 0 Participants | 80 Participants | 118 Participants |
| Age, Customized ≥ 20 to ≤ 29 years | 61 Participants | 134 Participants | 121 Participants | 316 Participants |
| Age, Customized ≥ 30 to ≤ 39 years | 47 Participants | 104 Participants | 92 Participants | 243 Participants |
| Age, Customized ≥ 40 to ≤ 49 years | 48 Participants | 77 Participants | 97 Participants | 222 Participants |
| Age, Customized ≥ 50 to ≤ 59 years | 30 Participants | 51 Participants | 52 Participants | 133 Participants |
| Age, Customized ≥ 60 to ≤ 64 years | 7 Participants | 11 Participants | 14 Participants | 32 Participants |
| Composite Symptom Score ≤ 11 | 72 Participants | 119 Participants | 144 Participants | 335 Participants |
| Composite Symptom Score ≥ 12 | 159 Participants | 258 Participants | 312 Participants | 729 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 25 Participants | 32 Participants | 68 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 220 Participants | 352 Participants | 424 Participants | 996 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Influenza Virus Type or Subtype on RT-PCR Assay at Enrollment A/H1N1pdm | 7 Participants | 2 Participants | 7 Participants | 16 Participants |
| Influenza Virus Type or Subtype on RT-PCR Assay at Enrollment A/H3 | 196 Participants | 332 Participants | 393 Participants | 921 Participants |
| Influenza Virus Type or Subtype on RT-PCR Assay at Enrollment B | 20 Participants | 34 Participants | 38 Participants | 92 Participants |
| Influenza Virus Type or Subtype on RT-PCR Assay at Enrollment Mixed infection | 3 Participants | 6 Participants | 8 Participants | 17 Participants |
| Influenza Virus Type or Subtype on RT-PCR Assay at Enrollment Other | 5 Participants | 3 Participants | 10 Participants | 18 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 178 Participants | 305 Participants | 349 Participants | 832 Participants |
| Race/Ethnicity, Customized Black or African American | 11 Participants | 9 Participants | 18 Participants | 38 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 2 Participants | 4 Participants | 8 Participants |
| Race/Ethnicity, Customized White | 40 Participants | 60 Participants | 85 Participants | 185 Participants |
| Region Japan/Asia | 175 Participants | 303 Participants | 343 Participants | 821 Participants |
| Region Rest of the world | 56 Participants | 74 Participants | 113 Participants | 243 Participants |
| Sex: Female, Male Female | 111 Participants | 159 Participants | 224 Participants | 494 Participants |
| Sex: Female, Male Male | 120 Participants | 218 Participants | 232 Participants | 570 Participants |
| Time From Symptom Onset to Initiation of the Trial Regimen ≥ 0 to ≤ 12 hours | 34 Participants | 41 Participants | 60 Participants | 135 Participants |
| Time From Symptom Onset to Initiation of the Trial Regimen > 12 to ≤ 24 hours | 87 Participants | 163 Participants | 178 Participants | 428 Participants |
| Time From Symptom Onset to Initiation of the Trial Regimen > 24 to ≤ 36 hours | 67 Participants | 94 Participants | 139 Participants | 300 Participants |
| Time From Symptom Onset to Initiation of the Trial Regimen > 36 to ≤ 48 hours | 43 Participants | 79 Participants | 79 Participants | 201 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 610 | 0 / 309 | 0 / 513 |
| other Total, other adverse events | 47 / 610 | 40 / 309 | 45 / 513 |
| serious Total, serious adverse events | 2 / 610 | 0 / 309 | 0 / 513 |
Outcome results
Primary
Time to Alleviation of Symptoms in Adults Randomized to Baloxavir or Oseltamivir
Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of symptoms was defined as the time from the start of the study treatment to the time when all seven influenza-related symptoms were assessed by the participant as absent (0) or mild (1) for at least 21.5 hours. Time to alleviation of symptoms was analyzed using the Kaplan-Meier(KM) method; participants who did not experience alleviation of symptoms were censored at the last observation time point.
Time frame: Initiation of study treatment up to Day 14
Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, and with available time to alleviation of symptoms data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baloxavir | Time to Alleviation of Symptoms in Adults Randomized to Baloxavir or Oseltamivir | 53.5 hours |
| Placebo | Time to Alleviation of Symptoms in Adults Randomized to Baloxavir or Oseltamivir | 53.8 hours |
Comparison: A secondary analysis of time to alleviation of symptoms, consisting of a comparison between the 20 to 64 years of age stratum of the baloxavir group and the oseltamivir group, was conducted if statistical significance was observed in the primary analysis in order to maintain the overall Type I error.p-value: 0.75695% CI: [-6.6, 6.6]Generalized Wilcoxon test
Comparison: Analysis using the stratified log rank test was performed as a sensitivity analysis.p-value: 0.3761Log Rank
Primary
Time to Alleviation of Symptoms in Participants Randomized to Baloxavir or Placebo
Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of symptoms was defined as the time from the start of the study treatment to the time when all seven influenza-related symptoms were assessed by the participant as absent (0) or mild (1) for at least 21.5 hours. Time to alleviation of symptoms was analyzed using the Kaplan-Meier (KM) method; participants who did not experience alleviation of symptoms were censored at the last observation time point.
Time frame: Initiation of study treatment up to Day 14
Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo with available time to alleviation of symptoms data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baloxavir | Time to Alleviation of Symptoms in Participants Randomized to Baloxavir or Placebo | 53.7 hours |
| Placebo | Time to Alleviation of Symptoms in Participants Randomized to Baloxavir or Placebo | 80.2 hours |
Comparison: The primary analysis of time to alleviation of symptoms was a comparison of baloxavir with placebo in all participants in the intention-to-treat infection population. Statistical tests were performed at the 0.05 significance level.p-value: <0.000195% CI: [-35.8, -17.8]Generalized Wilcoxon test
Comparison: Analysis using the stratified log rank test was performed as a sensitivity analysis.p-value: <0.0001Log Rank
Secondary
Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Adults Randomized to Baloxavir or Oseltamivir
This endpoint was defined as AUC of change from Baseline in virus titer from Day 1 to Day 9. AUC was calculated using the trapezoidal method.
Time frame: Day 1 to Day 9
Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, with a positive virus titer on Day 1 and available sample on Day 9.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baloxavir | Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Adults Randomized to Baloxavir or Oseltamivir | -829.6 log₁₀[TCID₅₀/mL]*hours | Standard Deviation 350.3 |
| Placebo | Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Adults Randomized to Baloxavir or Oseltamivir | -790.2 log₁₀[TCID₅₀/mL]*hours | Standard Deviation 328.4 |
p-value: 0.0313van Elteren test
Secondary
Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Participants Randomized to Baloxavir or Placebo
This endpoint was defined as AUC of change from Baseline in virus titer from Day 1 to Day 9. AUC was calculated using the trapezoidal method.
Time frame: Day 1 to Day 9
Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo, with a positive virus titer on Day 1 and available sample on Day 9.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baloxavir | Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Participants Randomized to Baloxavir or Placebo | -836.2 log₁₀[TCID₅₀/mL]*hours | Standard Deviation 348.9 |
| Placebo | Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Participants Randomized to Baloxavir or Placebo | -641.8 log₁₀[TCID₅₀/mL]*hours | Standard Deviation 377.6 |
p-value: <0.0001van Elteren test
Secondary
Area Under the Curve (AUC) Adjusted by Baseline of Influenza Virus RNA in Adults Randomized to Baloxavir or Oseltamivir
This endpoint was defined as AUC of change from baseline in the amount of virus RNA (RT-PCR) from Day 1 to Day 9. The AUC was calculated using the trapezoidal method.
Time frame: Day 1 to Day 9
Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, with a positive virus RNA determined by RT-PCR at baseline and available sample on Day 9.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baloxavir | Area Under the Curve (AUC) Adjusted by Baseline of Influenza Virus RNA in Adults Randomized to Baloxavir or Oseltamivir | -581.0 log₁₀ virus particles/mL*hours | Standard Deviation 231.2 |
| Placebo | Area Under the Curve (AUC) Adjusted by Baseline of Influenza Virus RNA in Adults Randomized to Baloxavir or Oseltamivir | -569.7 log₁₀ virus particles/mL*hours | Standard Deviation 228.8 |
p-value: 0.2424van Elteren test
Secondary
Area Under the Curve (AUC) Adjusted by Baseline of Influenza Virus RNA in Participants Randomized to Baloxavir or Placebo
This endpoint was defined as AUC of change from baseline in the amount of virus RNA (RT-PCR) from Day 1 to Day 9. The AUC was calculated using the trapezoidal method.
Time frame: Day 1 to Day 9
Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo with a positive virus RNA determined by RT-PCR at baseline and available sample on Day 9.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baloxavir | Area Under the Curve (AUC) Adjusted by Baseline of Influenza Virus RNA in Participants Randomized to Baloxavir or Placebo | -582.0 log₁₀ virus particles/mL*hours | Standard Deviation 230.9 |
| Placebo | Area Under the Curve (AUC) Adjusted by Baseline of Influenza Virus RNA in Participants Randomized to Baloxavir or Placebo | -456.8 log₁₀ virus particles/mL*hours | Standard Deviation 269.6 |
p-value: <0.0001van Elteren test
Secondary
Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Participant's self-measured axillary temperature using an electronic thermometer.
Time frame: 12, 24, 36, 48, 72, 96 and 120 hours after the initial dose of study treatment
Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, with available temperature data at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir | Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 48 hours | 36.34 °C | Standard Error 0.03 |
| Baloxavir | Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 72 hours | 36.30 °C | Standard Error 0.03 |
| Baloxavir | Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 24 hours | 36.78 °C | Standard Error 0.04 |
| Baloxavir | Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 96 hours | 36.26 °C | Standard Error 0.03 |
| Baloxavir | Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 12 hours | 37.47 °C | Standard Error 0.05 |
| Baloxavir | Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 120 hours | 36.27 °C | Standard Error 0.03 |
| Baloxavir | Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 36 hours | 36.55 °C | Standard Error 0.04 |
| Placebo | Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 120 hours | 36.21 °C | Standard Error 0.03 |
| Placebo | Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 12 hours | 37.35 °C | Standard Error 0.05 |
| Placebo | Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 24 hours | 36.73 °C | Standard Error 0.04 |
| Placebo | Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 48 hours | 36.36 °C | Standard Error 0.03 |
| Placebo | Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 72 hours | 36.31 °C | Standard Error 0.03 |
| Placebo | Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 96 hours | 36.23 °C | Standard Error 0.03 |
| Placebo | Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 36 hours | 36.54 °C | Standard Error 0.04 |
Comparison: 12 hoursp-value: 0.093795% CI: [-0.02, 0.24]ANCOVA
Comparison: 24 hoursp-value: 0.334395% CI: [-0.05, 0.16]ANCOVA
Comparison: 36 hoursp-value: 0.925895% CI: [-0.09, 0.1]ANCOVA
Comparison: 48 hoursp-value: 0.657495% CI: [-0.1, 0.06]ANCOVA
Comparison: 72 hoursp-value: 0.85295% CI: [-0.09, 0.07]ANCOVA
Comparison: 96 hoursp-value: 0.453295% CI: [-0.05, 0.11]ANCOVA
Comparison: 120 hoursp-value: 0.15795% CI: [-0.02, 0.13]ANCOVA
Secondary
Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
Participant's self-measured axillary temperature using an electronic thermometer.
Time frame: 12, 24, 36, 48, 72, 96 and 120 hours after the initial dose of study treatment
Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo with available temperature data at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir | Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 36 hours | 36.49 °C | Standard Error 0.04 |
| Baloxavir | Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 72 hours | 36.26 °C | Standard Error 0.03 |
| Baloxavir | Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 24 hours | 36.73 °C | Standard Error 0.04 |
| Baloxavir | Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 96 hours | 36.27 °C | Standard Error 0.03 |
| Baloxavir | Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 48 hours | 36.32 °C | Standard Error 0.03 |
| Baloxavir | Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 120 hours | 36.28 °C | Standard Error 0.03 |
| Baloxavir | Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 12 hours | 37.40 °C | Standard Error 0.05 |
| Placebo | Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 120 hours | 36.25 °C | Standard Error 0.04 |
| Placebo | Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 12 hours | 37.49 °C | Standard Error 0.07 |
| Placebo | Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 24 hours | 37.07 °C | Standard Error 0.05 |
| Placebo | Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 36 hours | 36.90 °C | Standard Error 0.05 |
| Placebo | Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 48 hours | 36.69 °C | Standard Error 0.05 |
| Placebo | Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 72 hours | 36.48 °C | Standard Error 0.04 |
| Placebo | Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 96 hours | 36.31 °C | Standard Error 0.04 |
Comparison: 12 hoursp-value: 0.255795% CI: [-0.24, 0.06]ANCOVA
Comparison: 24 hoursp-value: <0.000195% CI: [-0.46, -0.22]ANCOVA
Comparison: 36 hoursp-value: <0.000195% CI: [-0.52, -0.29]ANCOVA
Comparison: 48 hoursp-value: <0.000195% CI: [-0.48, -0.27]ANCOVA
Comparison: 72 hoursp-value: <0.000195% CI: [-0.31, -0.13]ANCOVA
Comparison: 96 hoursp-value: 0.448495% CI: [-0.13, 0.06]ANCOVA
Comparison: ANCOVA with baseline composite symptom score and region (Japan/Asia, Rest of the world) and body temperature at baseline as covariates.p-value: 0.596395% CI: [-0.07, 0.11]ANCOVA
Secondary
Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). The composite symptom score is the total score of the 7 influenza symptoms as assessed by the participant, and ranges from 0 to 21.
Time frame: Day 1 pretreatment (Baseline) and 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, and 216 hours after the initial dose of study treatment.
Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, with available composite symptom scores at Baseline and each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 48 hours | -7.6 scores on a scale | Standard Error 0.2 |
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 120 hours | -11.0 scores on a scale | Standard Error 0.2 |
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 36 hours | -6.5 scores on a scale | Standard Error 0.2 |
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 144 hours | -11.8 scores on a scale | Standard Error 0.2 |
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 72 hours | -9.6 scores on a scale | Standard Error 0.2 |
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 168 hours | -11.9 scores on a scale | Standard Error 0.2 |
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 24 hours | -4.5 scores on a scale | Standard Error 0.2 |
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 192 hours | -12.0 scores on a scale | Standard Error 0.1 |
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 96 hours | -10.5 scores on a scale | Standard Error 0.2 |
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 216 hours | -12.4 scores on a scale | Standard Error 0.2 |
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 12 hours | -2.2 scores on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 216 hours | -12.5 scores on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 12 hours | -2.4 scores on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 24 hours | -4.7 scores on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 36 hours | -6.3 scores on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 48 hours | -7.8 scores on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 72 hours | -9.7 scores on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 96 hours | -10.6 scores on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 120 hours | -11.3 scores on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 144 hours | -11.8 scores on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 168 hours | -12.1 scores on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 192 hours | -12.4 scores on a scale | Standard Error 0.2 |
Comparison: 12 hoursp-value: 0.409195% CI: [-0.3, 0.8]ANCOVA
Comparison: 24 hoursp-value: 0.307395% CI: [-0.3, 0.8]ANCOVA
Comparison: 36 hoursp-value: 0.346595% CI: [-0.8, 0.3]ANCOVA
Comparison: 48 hoursp-value: 0.428595% CI: [-0.3, 0.7]ANCOVA
Comparison: 72 hoursp-value: 0.670395% CI: [-0.4, 0.6]ANCOVA
Comparison: 96 hoursp-value: 0.718795% CI: [-0.3, 0.5]ANCOVA
Comparison: 120 hoursp-value: 0.13595% CI: [-0.1, 0.7]ANCOVA
Comparison: 144 hoursp-value: 0.704695% CI: [-0.3, 0.5]ANCOVA
Comparison: 168 hoursp-value: 0.276595% CI: [-0.2, 0.6]ANCOVA
Comparison: 192 hoursp-value: 0.027495% CI: [0, 0.8]ANCOVA
Comparison: 216 hoursp-value: 0.600195% CI: [-0.3, 0.6]ANCOVA
Secondary
Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo
Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). The composite symptom score is the total score of the 7 influenza symptoms as assessed by the participant, and ranges from 0 to 21.
Time frame: Day 1 pretreatment (Baseline) and 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, and 216 hours after the initial dose of study treatment.
Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo with available composite symptom scores at Baseline and each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 48 hours | -7.8 scores on a scale | Standard Error 0.2 |
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 120 hours | -10.9 scores on a scale | Standard Error 0.2 |
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 36 hours | -6.7 scores on a scale | Standard Error 0.2 |
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 144 hours | -11.6 scores on a scale | Standard Error 0.1 |
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 72 hours | -9.4 scores on a scale | Standard Error 0.2 |
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 168 hours | -11.9 scores on a scale | Standard Error 0.1 |
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 24 hours | -4.7 scores on a scale | Standard Error 0.2 |
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 192 hours | -12.0 scores on a scale | Standard Error 0.1 |
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 96 hours | -10.5 scores on a scale | Standard Error 0.2 |
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 216 hours | -12.4 scores on a scale | Standard Error 0.2 |
| Baloxavir | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 12 hours | -2.4 scores on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 216 hours | -12.4 scores on a scale | Standard Error 0.3 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 12 hours | -2.5 scores on a scale | Standard Error 0.3 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 24 hours | -3.6 scores on a scale | Standard Error 0.3 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 36 hours | -4.9 scores on a scale | Standard Error 0.3 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 48 hours | -6.0 scores on a scale | Standard Error 0.3 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 72 hours | -8.0 scores on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 96 hours | -9.5 scores on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 120 hours | -10.6 scores on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 144 hours | -11.2 scores on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 168 hours | -11.8 scores on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo | 192 hours | -12.0 scores on a scale | Standard Error 0.2 |
Comparison: 12 hoursp-value: 0.717395% CI: [-0.5, 0.7]ANCOVA
Comparison: 24 hoursp-value: 0.000995% CI: [-1.7, -0.4]ANCOVA
Comparison: 36 hoursp-value: <0.000195% CI: [-2.4, -1.1]ANCOVA
Comparison: 48 hoursp-value: <0.000195% CI: [-2.4, -1.2]ANCOVA
Comparison: 72 hoursp-value: <0.000195% CI: [-2, -0.9]ANCOVA
Comparison: 96 hoursp-value: 0.000195% CI: [-1.5, -0.5]ANCOVA
Comparison: 120 hoursp-value: 0.197995% CI: [-0.8, 0.2]ANCOVA
Comparison: 144 hoursp-value: 0.107995% CI: [-0.8, 0.1]ANCOVA
Comparison: 168 hoursp-value: 0.580595% CI: [-0.6, 0.3]ANCOVA
Comparison: 192 hoursp-value: 0.805795% CI: [-0.4, 0.5]ANCOVA
Comparison: 216 hoursp-value: 0.952595% CI: [-0.6, 0.6]ANCOVA
Secondary
Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Nasopharyngeal swabs (or throat swabs, if nasopharyngeal swabbing was not feasible) were obtained for viral quantitation. Virus RNA was measured by reverse transcription polymerase chain reaction (RT-PCR).
Time frame: Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Population: Participants in the intention-to-treat infection population ≥ 20 years of age and assigned to baloxavir or oseltamivir, with positive influenza virus titer on Day 1 and with available virus RNA data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 2 | -1.61 log₁₀ virus particles/mL | Standard Deviation 1.06 |
| Baloxavir | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 3 | -2.79 log₁₀ virus particles/mL | Standard Deviation 1.21 |
| Baloxavir | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 4 | -2.94 log₁₀ virus particles/mL | Standard Deviation 1.62 |
| Baloxavir | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 5 | -3.76 log₁₀ virus particles/mL | Standard Deviation 1.44 |
| Baloxavir | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 6 | -3.81 log₁₀ virus particles/mL | Standard Deviation 1.52 |
| Baloxavir | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 9 | -4.43 log₁₀ virus particles/mL | Standard Deviation 1.43 |
| Placebo | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 6 | -3.88 log₁₀ virus particles/mL | Standard Deviation 1.35 |
| Placebo | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 2 | -1.10 log₁₀ virus particles/mL | Standard Deviation 1.1 |
| Placebo | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 5 | -3.62 log₁₀ virus particles/mL | Standard Deviation 1.34 |
| Placebo | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 3 | -2.44 log₁₀ virus particles/mL | Standard Deviation 1.24 |
| Placebo | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 9 | -4.52 log₁₀ virus particles/mL | Standard Deviation 1.22 |
| Placebo | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 4 | -2.97 log₁₀ virus particles/mL | Standard Deviation 1.29 |
Comparison: Day 2p-value: <0.0001van Elteren test
Comparison: Day 3p-value: <0.0001van Elteren test
Comparison: Day 4p-value: 0.4148van Elteren test
Comparison: Day 5p-value: 0.0338van Elteren test
Comparison: Day 6p-value: 0.9619van Elteren test
Comparison: Day 9p-value: 0.8491van Elteren test
Secondary
Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo
Nasopharyngeal swabs (or throat swabs, if nasopharyngeal swabbing was not feasible) were obtained for viral quantitation. Virus RNA is measured by reverse transcription polymerase chain reaction (RT-PCR).
Time frame: Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo, with positive influenza virus titer on Day 1 and with available virus RNA data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 2 | -1.63 log₁₀ virus particles/mL | Standard Deviation 1.03 |
| Baloxavir | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 3 | -2.80 log₁₀ virus particles/mL | Standard Deviation 1.2 |
| Baloxavir | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 4 | -3.07 log₁₀ virus particles/mL | Standard Deviation 1.59 |
| Baloxavir | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 5 | -3.75 log₁₀ virus particles/mL | Standard Deviation 1.47 |
| Baloxavir | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 6 | -3.83 log₁₀ virus particles/mL | Standard Deviation 1.64 |
| Baloxavir | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 9 | -4.43 log₁₀ virus particles/mL | Standard Deviation 1.42 |
| Placebo | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 6 | -3.03 log₁₀ virus particles/mL | Standard Deviation 1.85 |
| Placebo | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 2 | -0.56 log₁₀ virus particles/mL | Standard Deviation 1.37 |
| Placebo | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 5 | -3.04 log₁₀ virus particles/mL | Standard Deviation 1.62 |
| Placebo | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 3 | -1.61 log₁₀ virus particles/mL | Standard Deviation 1.76 |
| Placebo | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 9 | -4.06 log₁₀ virus particles/mL | Standard Deviation 1.47 |
| Placebo | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 4 | -1.95 log₁₀ virus particles/mL | Standard Deviation 1.76 |
Comparison: Day 2p-value: <0.0001van Elteren test
Comparison: Day 3p-value: <0.0001van Elteren test
Comparison: Day 4p-value: <0.0001van Elteren test
Comparison: Day 5p-value: <0.0001van Elteren test
Comparison: Day 6p-value: 0.001van Elteren test
Comparison: Day 9p-value: 0.0002van Elteren test
Secondary
Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Virus titer was quantified from nasopharyngeal swabs (or throat swabs if nasopharyngeal swabbing was not feasible) by tissue culture methods. If virus titer was less than the lower limit of quantification, the virus titer was imputed 0.7 (TCID₅₀/mL).
Time frame: Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, with positive influenza virus titer on Day 1 and with available virus titer data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir | Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 2 | -4.39 log₁₀[TCID₅₀/mL] | Standard Deviation 2.07 |
| Baloxavir | Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 3 | -4.79 log₁₀[TCID₅₀/mL] | Standard Deviation 2.03 |
| Baloxavir | Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 4 | -4.46 log₁₀[TCID₅₀/mL] | Standard Deviation 2.03 |
| Baloxavir | Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 5 | -4.95 log₁₀[TCID₅₀/mL] | Standard Deviation 1.94 |
| Baloxavir | Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 6 | -4.56 log₁₀[TCID₅₀/mL] | Standard Deviation 1.99 |
| Baloxavir | Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 9 | -5.03 log₁₀[TCID₅₀/mL] | Standard Deviation 1.89 |
| Placebo | Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 6 | -4.85 log₁₀[TCID₅₀/mL] | Standard Deviation 1.95 |
| Placebo | Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 2 | -2.53 log₁₀[TCID₅₀/mL] | Standard Deviation 2.03 |
| Placebo | Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 5 | -4.98 log₁₀[TCID₅₀/mL] | Standard Deviation 1.81 |
| Placebo | Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 3 | -4.20 log₁₀[TCID₅₀/mL] | Standard Deviation 2.02 |
| Placebo | Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 9 | -5.22 log₁₀[TCID₅₀/mL] | Standard Deviation 1.7 |
| Placebo | Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 4 | -4.63 log₁₀[TCID₅₀/mL] | Standard Deviation 1.89 |
Comparison: Day 2p-value: <0.0001van Elteren test
Comparison: Day 3p-value: <0.0001van Elteren test
Comparison: Day 4p-value: 0.801van Elteren test
Comparison: Day 5p-value: 0.9451van Elteren test
Comparison: Day 6p-value: 0.2256van Elteren test
Comparison: Day 9p-value: 0.3332van Elteren test
Secondary
Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo
Virus titer was quantified from nasopharyngeal swabs (or throat swabs if nasopharyngeal swabbing was not feasible) by tissue culture methods. If virus titer was less than the lower limit of quantification, the virus titer was imputed 0.7 (TCID₅₀/mL).
Time frame: Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo, with positive influenza virus titer on Day 1 and with available virus titer data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baloxavir | Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 2 | -4.45 log₁₀[TCID₅₀/mL] | Standard Deviation 2.03 |
| Baloxavir | Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 3 | -4.82 log₁₀[TCID₅₀/mL] | Standard Deviation 1.99 |
| Baloxavir | Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 4 | -4.50 log₁₀[TCID₅₀/mL] | Standard Deviation 2.02 |
| Baloxavir | Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 5 | -4.95 log₁₀[TCID₅₀/mL] | Standard Deviation 1.93 |
| Baloxavir | Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 6 | -4.58 log₁₀[TCID₅₀/mL] | Standard Deviation 1.99 |
| Baloxavir | Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 9 | -5.06 log₁₀[TCID₅₀/mL] | Standard Deviation 1.87 |
| Placebo | Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 6 | -4.68 log₁₀[TCID₅₀/mL] | Standard Deviation 2.12 |
| Placebo | Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 2 | -1.19 log₁₀[TCID₅₀/mL] | Standard Deviation 2.43 |
| Placebo | Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 5 | -4.47 log₁₀[TCID₅₀/mL] | Standard Deviation 2.21 |
| Placebo | Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 3 | -2.88 log₁₀[TCID₅₀/mL] | Standard Deviation 2.88 |
| Placebo | Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 9 | -4.87 log₁₀[TCID₅₀/mL] | Standard Deviation 1.85 |
| Placebo | Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 4 | -3.31 log₁₀[TCID₅₀/mL] | Standard Deviation 2.34 |
Comparison: Day 2p-value: <0.0001van Elteren test
Comparison: Day 3p-value: <0.0001van Elteren test
Comparison: Day 4p-value: 0.0008van Elteren test
Comparison: Day 5p-value: 0.0132van Elteren test
Comparison: Day 6p-value: 0.9307van Elteren test
Comparison: Day 9p-value: 0.1677van Elteren test
Secondary
Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Defined as the percentage of patients whose axillary temperature dropped to less than 37ºC after the initiation of study treatment.
Time frame: 12, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours after the initial dose of study treatment
Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, whose body temperature at baseline was more than 37°C with available body temperature data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 48 hours | 90.1 percentage of participants |
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 120 hours | 93.8 percentage of participants |
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 36 hours | 81.9 percentage of participants |
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 144 hours | 92.8 percentage of participants |
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 72 hours | 93.8 percentage of participants |
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 168 hours | 93.6 percentage of participants |
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 24 hours | 64.3 percentage of participants |
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 192 hours | 94.6 percentage of participants |
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 96 hours | 93.9 percentage of participants |
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 216 hours | 92.8 percentage of participants |
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 12 hours | 25.0 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 216 hours | 94.5 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 12 hours | 28.3 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 24 hours | 66.8 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 36 hours | 79.1 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 48 hours | 89.9 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 72 hours | 89.5 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 96 hours | 94.9 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 120 hours | 95.8 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 144 hours | 94.5 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 168 hours | 95.9 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 192 hours | 95.8 percentage of participants |
Comparison: 12 hoursp-value: 0.2953Mantel Haenszel
Comparison: 24 hoursp-value: 0.5414Mantel Haenszel
Comparison: 36 hoursp-value: 0.2079Mantel Haenszel
Comparison: 48 hoursp-value: 0.7771Mantel Haenszel
Comparison: 72 hoursp-value: 0.0215Mantel Haenszel
Comparison: 96 hoursp-value: 0.8033Mantel Haenszel
Comparison: 120 hoursp-value: 0.4157Mantel Haenszel
Comparison: 144 hoursp-value: 0.5908Mantel Haenszel
Comparison: 168 hoursp-value: 0.2975Mantel Haenszel
Comparison: 192 hoursp-value: 0.8644Mantel Haenszel
Comparison: 216 hoursp-value: 0.5573Mantel Haenszel
Secondary
Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
Defined as the percentage of patients whose axillary temperature dropped to less than 37ºC after the initiation of study treatment.
Time frame: 12, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours after the initial dose of study treatment
Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo whose body temperature at baseline was more than 37°C with available body temperature data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 48 hours | 89.3 percentage of participants |
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 120 hours | 92.9 percentage of participants |
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 36 hours | 80.8 percentage of participants |
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 144 hours | 93.4 percentage of participants |
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 72 hours | 93.7 percentage of participants |
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 168 hours | 93.3 percentage of participants |
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 24 hours | 64.3 percentage of participants |
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 192 hours | 94.1 percentage of participants |
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 96 hours | 92.8 percentage of participants |
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 216 hours | 92.5 percentage of participants |
| Baloxavir | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 12 hours | 26.5 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 216 hours | 92.7 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 12 hours | 25.3 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 24 hours | 48.4 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 36 hours | 58.3 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 48 hours | 67.3 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 72 hours | 83.8 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 96 hours | 93.9 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 120 hours | 92.8 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 144 hours | 93.6 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 168 hours | 93.6 percentage of participants |
| Placebo | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo | 192 hours | 93.7 percentage of participants |
Comparison: 12 hoursp-value: 0.7866Mantel Haenszel
Comparison: 24 hoursp-value: <0.0001Mantel Haenszel
Comparison: 36 hoursp-value: <0.0001Mantel Haenszel
Comparison: 48 hoursp-value: <0.0001Mantel Haenszel
Comparison: 72 hoursp-value: <0.0001Mantel Haenszel
Comparison: 96 hoursp-value: 0.7044Mantel Haenszel
Comparison: 120 hoursp-value: 0.8512Mantel Haenszel
Comparison: 144 hoursp-value: 0.8783Mantel Haenszel
Comparison: 168 hoursp-value: 0.8291Mantel Haenszel
Comparison: 192 hoursp-value: 0.8644Mantel Haenszel
Comparison: 216 hoursp-value: 0.9312Mantel Haenszel
Secondary
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Alleviation of symptoms was defined as all seven influenza-related symptoms assessed by the participant as absent (0) or mild (1) .
Time frame: 12, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours after the initial dose of study treatment
Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, with available alleviation of symptoms data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 120 hours | 86.1 percentage of participants |
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 12 hours | 8.7 percentage of participants |
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 24 hours | 21.3 percentage of participants |
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 36 hours | 41.1 percentage of participants |
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 48 hours | 51.0 percentage of participants |
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 72 hours | 70.7 percentage of participants |
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 96 hours | 79.8 percentage of participants |
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 144 hours | 89.2 percentage of participants |
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 168 hours | 91.4 percentage of participants |
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 192 hours | 90.8 percentage of participants |
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 216 hours | 90.9 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 168 hours | 94.3 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 96 hours | 80.5 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 12 hours | 4.9 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 120 hours | 87.0 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 24 hours | 22.7 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 216 hours | 96.3 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 36 hours | 38.7 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 144 hours | 91.3 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 48 hours | 54.4 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 192 hours | 95.5 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | 72 hours | 73.0 percentage of participants |
Comparison: 12 hoursp-value: 0.0458Mantel Haenszel
Comparison: 24 hoursp-value: 0.7565Mantel Haenszel
Comparison: 36 hoursp-value: 0.3297Mantel Haenszel
Comparison: 48 hoursp-value: 0.4442Mantel Haenszel
Comparison: 72 hoursp-value: 0.6029Mantel Haenszel
Comparison: 96 hoursp-value: 0.9881Mantel Haenszel
Comparison: 120 hoursp-value: 0.9257Mantel Haenszel
Comparison: 144 hoursp-value: 0.5317Mantel Haenszel
Comparison: 168 hoursp-value: 0.2144Mantel Haenszel
Comparison: 192 hoursp-value: 0.0413Mantel Haenszel
Comparison: 216 hoursp-value: 0.0409Mantel Haenszel
Secondary
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo
Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Alleviation of symptoms was defined as all seven influenza-related symptoms assessed by the participant as absent (0) or mild (1) .
Time frame: 12, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours after the initial dose of study treatment
Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo with available alleviation of symptoms data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 36 hours | 42.4 percentage of participants |
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 48 hours | 50.7 percentage of participants |
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 96 hours | 78.6 percentage of participants |
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 120 hours | 85.5 percentage of participants |
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 12 hours | 9.7 percentage of participants |
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 24 hours | 23.1 percentage of participants |
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 72 hours | 68.9 percentage of participants |
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 144 hours | 89.1 percentage of participants |
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 168 hours | 91.6 percentage of participants |
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 192 hours | 90.9 percentage of participants |
| Baloxavir | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 216 hours | 91.1 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 192 hours | 91.4 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 36 hours | 23.1 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 24 hours | 12.8 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 48 hours | 26.4 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 72 hours | 49.5 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 168 hours | 88.3 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 96 hours | 69.9 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 216 hours | 91.9 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 120 hours | 81.6 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 144 hours | 85.4 percentage of participants |
| Placebo | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo | 12 hours | 8.1 percentage of participants |
Comparison: 24 hoursp-value: 0.001Mantel Haenszel
Comparison: 36 hoursp-value: <0.0001Mantel Haenszel
Comparison: 12 hoursp-value: 0.5973Mantel Haenszel
Comparison: 48 hoursp-value: <0.0001Mantel Haenszel
Comparison: 72 hoursp-value: <0.0001Mantel Haenszel
Comparison: 96 hoursp-value: 0.0115Mantel Haenszel
Comparison: 120 hoursp-value: 0.1298Mantel Haenszel
Comparison: 144 hoursp-value: 0.117Mantel Haenszel
Comparison: 168 hoursp-value: 0.0757Mantel Haenszel
Comparison: 192 hoursp-value: 0.9453Mantel Haenszel
Comparison: 216 hoursp-value: 0.8657Mantel Haenszel
Secondary
Percentage of Participants With Adverse Events (AEs)
Time frame: From first dose of study drug to Day 22
Population: All participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baloxavir | Percentage of Participants With Adverse Events (AEs) | Adverse events (AEs) | 20.7 percentage of participants |
| Baloxavir | Percentage of Participants With Adverse Events (AEs) | Serious adverse events (SAEs) | 0.3 percentage of participants |
| Baloxavir | Percentage of Participants With Adverse Events (AEs) | AEs leading to withdrawal of study drug | 0.3 percentage of participants |
| Baloxavir | Percentage of Participants With Adverse Events (AEs) | Treatment-related adverse events (TRAEs) | 4.4 percentage of participants |
| Baloxavir | Percentage of Participants With Adverse Events (AEs) | Treatment-related serious adverse events | 0.0 percentage of participants |
| Baloxavir | Percentage of Participants With Adverse Events (AEs) | TRAEs leading to withdrawal of study drug | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Adverse Events (AEs) | TRAEs leading to withdrawal of study drug | 0.3 percentage of participants |
| Placebo | Percentage of Participants With Adverse Events (AEs) | Adverse events (AEs) | 24.6 percentage of participants |
| Placebo | Percentage of Participants With Adverse Events (AEs) | Treatment-related adverse events (TRAEs) | 3.9 percentage of participants |
| Placebo | Percentage of Participants With Adverse Events (AEs) | Treatment-related serious adverse events | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Adverse Events (AEs) | Serious adverse events (SAEs) | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Adverse Events (AEs) | AEs leading to withdrawal of study drug | 0.3 percentage of participants |
| Oseltamivir | Percentage of Participants With Adverse Events (AEs) | Serious adverse events (SAEs) | 0.0 percentage of participants |
| Oseltamivir | Percentage of Participants With Adverse Events (AEs) | AEs leading to withdrawal of study drug | 0.4 percentage of participants |
| Oseltamivir | Percentage of Participants With Adverse Events (AEs) | TRAEs leading to withdrawal of study drug | 0.2 percentage of participants |
| Oseltamivir | Percentage of Participants With Adverse Events (AEs) | Treatment-related adverse events (TRAEs) | 8.4 percentage of participants |
| Oseltamivir | Percentage of Participants With Adverse Events (AEs) | Adverse events (AEs) | 24.8 percentage of participants |
| Oseltamivir | Percentage of Participants With Adverse Events (AEs) | Treatment-related serious adverse events | 0.0 percentage of participants |
Secondary
Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir
The percentage of participants who experienced each influenza-related complication (hospitalization, death, sinusitis, otitis media, bronchitis, and radiologically confirmed pneumonia) as an adverse event after the initiation of the study treatment.
Time frame: Initiation of study treatment up to Day 14
Population: Participants in the intention-to-treat infection population ≥ 20 years of age and assigned to baloxavir or oseltamivir.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baloxavir | Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir | Hospitalization | 0 percentage of participants |
| Baloxavir | Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir | Otitis media | 0.5 percentage of participants |
| Baloxavir | Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir | Death | 0 percentage of participants |
| Baloxavir | Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir | Bronchitis | 2.4 percentage of participants |
| Baloxavir | Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir | Sinusitis | 0.8 percentage of participants |
| Baloxavir | Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir | Pneumonia | 0.5 percentage of participants |
| Baloxavir | Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir | Any complication | 4.0 percentage of participants |
| Placebo | Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir | Pneumonia | 0.3 percentage of participants |
| Placebo | Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir | Any complication | 2.4 percentage of participants |
| Placebo | Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir | Death | 0 percentage of participants |
| Placebo | Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir | Hospitalization | 0.3 percentage of participants |
| Placebo | Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir | Sinusitis | 0 percentage of participants |
| Placebo | Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir | Otitis media | 0.3 percentage of participants |
| Placebo | Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir | Bronchitis | 1.6 percentage of participants |
Comparison: Any Complicationsp-value: 0.2217Fisher Exact
Secondary
Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo
The percentage of participants who experienced each influenza-related complication (hospitalization, death, sinusitis, otitis media, bronchitis, and radiologically confirmed pneumonia) as an adverse event after the initiation of the study treatment.
Time frame: Initiation of study treatment up to Day 14
Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baloxavir | Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo | Hospitalization | 0 percentage of participants |
| Baloxavir | Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo | Otitis media | 0.4 percentage of participants |
| Baloxavir | Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo | Death | 0 percentage of participants |
| Baloxavir | Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo | Bronchitis | 2.0 percentage of participants |
| Baloxavir | Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo | Sinusitis | 0.9 percentage of participants |
| Baloxavir | Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo | Pneumonia | 0.4 percentage of participants |
| Baloxavir | Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo | Any complication | 3.5 percentage of participants |
| Placebo | Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo | Pneumonia | 0.4 percentage of participants |
| Placebo | Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo | Any complication | 4.3 percentage of participants |
| Placebo | Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo | Death | 0 percentage of participants |
| Placebo | Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo | Hospitalization | 0 percentage of participants |
| Placebo | Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo | Sinusitis | 0.9 percentage of participants |
| Placebo | Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo | Otitis media | 0 percentage of participants |
| Placebo | Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo | Bronchitis | 3.5 percentage of participants |
Comparison: Any Complicationsp-value: 0.6728Fisher Exact
Secondary
Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Influenza virus RNA was quantified from nasopharyngeal swabs (or throat swabs, if nasopharyngeal swabbing was not feasible). The percentage of participants with detectable virus RNA (2.05 for flu A and 2.83 for flu B log₁₀ virus particles/mL) among those assessed measured by reverse transcription polymerase chain reaction (RT-PCR) on Days 2, 3, 4, 5, 6 and 9.
Time frame: Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, with positive influenza virus RNA determined by RT-PCR on Day 1, and with available data at each time point were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baloxavir | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 2 | 97.3 percentage of participants |
| Baloxavir | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 3 | 95.3 percentage of participants |
| Baloxavir | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 4 | 93.6 percentage of participants |
| Baloxavir | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 5 | 86.6 percentage of participants |
| Baloxavir | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 6 | 69.3 percentage of participants |
| Baloxavir | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 9 | 60.2 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 6 | 80.7 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 2 | 98.6 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 5 | 92.1 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 3 | 97.5 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 9 | 64.7 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 4 | 93.0 percentage of participants |
Comparison: Day 2p-value: 0.2266Mantel Haenszel
Comparison: Day 3p-value: 0.1379Mantel Haenszel
Comparison: Day 4p-value: 0.5479Mantel Haenszel
Comparison: Day 5p-value: 0.0241Mantel Haenszel
Comparison: Day 6p-value: 0.0898Mantel Haenszel
Comparison: Day 9p-value: 0.2548Mantel Haenszel
Secondary
Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo
Influenza virus ribonucleic acid (RNA) was quantified from nasopharyngeal swabs (or throat swabs, if nasopharyngeal swabbing was not feasible). The percentage of participants with detectable virus RNA (2.05 for flu A and 2.83 for flu B log₁₀ virus particles/mL) among those assessed measured by reverse transcription polymerase chain reaction (RT-PCR) on Days 2, 3, 4, 5, 6 and 9.
Time frame: Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo, with positive influenza virus RNA determined by RT-PCR on Day 1 and with available data at each time point were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baloxavir | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 2 | 97.3 percentage of participants |
| Baloxavir | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 3 | 95.6 percentage of participants |
| Baloxavir | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 4 | 93.4 percentage of participants |
| Baloxavir | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 5 | 87.4 percentage of participants |
| Baloxavir | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 6 | 74.8 percentage of participants |
| Baloxavir | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 9 | 61.5 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 6 | 77.2 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 2 | 97.7 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 5 | 93.9 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 3 | 97.2 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 9 | 72.4 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 4 | 91.0 percentage of participants |
Comparison: Day 2p-value: 0.6145Mantel Haenszel
Comparison: Day 3p-value: 0.2505Mantel Haenszel
Comparison: Day 4p-value: 0.419Mantel Haenszel
Comparison: Day 5p-value: 0.0095Mantel Haenszel
Comparison: Day 6p-value: 0.7393Mantel Haenszel
Comparison: Day 9p-value: 0.0049Mantel Haenszel
Secondary
Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Virus titer was quantified from nasopharyngeal swabs (or throat swabs if nasopharyngeal swabbing was not feasible) by tissue culture methods. Positive influenza virus titer was defined as virus titer not less than the lower limit of quantification (0.7 log₁₀ of the 50% tissue culture infective dose (TCID₅₀/mL) among those assessed for virus titer on Days 2, 3, 4, 5, 6 and 9.
Time frame: Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, with positive influenza virus titer on Day 1 and with available virus titer data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baloxavir | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 2 | 47.4 percentage of participants |
| Baloxavir | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 3 | 20.0 percentage of participants |
| Baloxavir | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 4 | 16.1 percentage of participants |
| Baloxavir | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 5 | 12.9 percentage of participants |
| Baloxavir | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 6 | 5.6 percentage of participants |
| Baloxavir | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 9 | 3.0 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 6 | 9.0 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 2 | 91.1 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 5 | 20.8 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 3 | 57.3 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 9 | 3.2 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir | Day 4 | 27.6 percentage of participants |
Comparison: Day 2p-value: <0.0001Mantel Haenszel
Comparison: Day 3p-value: <0.0001Mantel Haenszel
Comparison: Day 4p-value: 0.0852Mantel Haenszel
Comparison: Day 5p-value: 0.0063Mantel Haenszel
Comparison: Day 6p-value: 0.6187Mantel Haenszel
Comparison: Day 9p-value: 0.8637Mantel Haenszel
Secondary
Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo
Virus titer was quantified from nasopharyngeal swabs (or throat swabs if nasopharyngeal swabbing was not feasible) by tissue culture methods. Positive influenza virus titer was defined as virus titer not less than the lower limit of quantification (0.7 log₁₀ of the 50% tissue culture infective dose (TCID₅₀/mL) among those assessed for virus titer on Days 2, 3, 4, 5, 6 and 9.
Time frame: Days 2, 3, 4 (optional), 5, 6 (optional), and 9
Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo, with positive influenza virus titer on Day 1 and with available virus titer data at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Baloxavir | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 2 | 47.6 percentage of participants |
| Baloxavir | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 3 | 21.7 percentage of participants |
| Baloxavir | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 4 | 16.7 percentage of participants |
| Baloxavir | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 5 | 13.5 percentage of participants |
| Baloxavir | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 6 | 8.2 percentage of participants |
| Baloxavir | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 9 | 2.9 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 6 | 12.5 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 2 | 96.0 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 5 | 29.7 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 3 | 70.5 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 9 | 4.6 percentage of participants |
| Placebo | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo | Day 4 | 56.1 percentage of participants |
Comparison: Day 2p-value: <0.0001Mantel Haenszel
Comparison: Day 3p-value: <0.0001Mantel Haenszel
Comparison: Day 4p-value: <0.0001Mantel Haenszel
Comparison: Day 5p-value: <0.0001Mantel Haenszel
Comparison: Day 6p-value: 0.4767Mantel Haenszel
Comparison: Day 9p-value: 0.3353Mantel Haenszel
Secondary
Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir
Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of each symptom was defined as the time from the start of treatment to the start of the time period when the individual symptom was assessed by the participant as 0 (None) or 1 (Mild) for a duration of at least 21.5 hours.
Time frame: Initiation of study treatment up to Day 14
Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, whose symptom score at baseline was moderate (2) or severe (3) with available time to alleviation of symptoms data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Baloxavir | Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir | Headache | 26.9 hours |
| Baloxavir | Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir | Feverishness or chills | 21.0 hours |
| Baloxavir | Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir | Sore Throat | 32.1 hours |
| Baloxavir | Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir | Muscle or joint pain | 23.3 hours |
| Baloxavir | Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir | Nasal Congestion | 33.0 hours |
| Baloxavir | Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir | Fatigue | 28.9 hours |
| Baloxavir | Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir | Cough | 38.2 hours |
| Placebo | Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir | Fatigue | 26.6 hours |
| Placebo | Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir | Cough | 31.4 hours |
| Placebo | Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir | Sore Throat | 30.4 hours |
| Placebo | Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir | Headache | 25.6 hours |
| Placebo | Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir | Nasal Congestion | 31.3 hours |
| Placebo | Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir | Feverishness or chills | 21.2 hours |
| Placebo | Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir | Muscle or joint pain | 24.0 hours |
Comparison: Coughp-value: 0.6623Generalized Wilcoxon test
Comparison: Sore throatp-value: 0.8184Generalized Wilcoxon test
Comparison: Headachep-value: 0.9989Generalized Wilcoxon test
Comparison: Nasal congestionp-value: 0.3706Generalized Wilcoxon test
Comparison: Feverishness or chillsp-value: 0.9973Generalized Wilcoxon test
Comparison: Muscle or joint painp-value: 0.676Generalized Wilcoxon test
Comparison: Fatiguep-value: 0.4241Generalized Wilcoxon test
Secondary
Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo
Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of each symptom was defined as the time from the start of treatment to the start of the time period when the individual symptom was assessed by the participant as 0 (None) or 1 (Mild) for a duration of at least 21.5 hours.
Time frame: Initiation of study treatment up to Day 14
Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo whose symptom score at baseline was moderate (2) or severe (3) with available time to alleviation of symptoms data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Baloxavir | Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo | Headache | 26.1 hours |
| Baloxavir | Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo | Feverishness or chills | 20.9 hours |
| Baloxavir | Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo | Sore Throat | 31.5 hours |
| Baloxavir | Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo | Muscle or joint pain | 23.2 hours |
| Baloxavir | Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo | Nasal Congestion | 31.8 hours |
| Baloxavir | Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo | Fatigue | 25.3 hours |
| Baloxavir | Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo | Cough | 38.3 hours |
| Placebo | Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo | Fatigue | 40.5 hours |
| Placebo | Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo | Cough | 61.4 hours |
| Placebo | Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo | Sore Throat | 40.5 hours |
| Placebo | Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo | Headache | 37.9 hours |
| Placebo | Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo | Nasal Congestion | 52.5 hours |
| Placebo | Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo | Feverishness or chills | 25.8 hours |
| Placebo | Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo | Muscle or joint pain | 31.3 hours |
Comparison: Nasal Congestionp-value: 0.0027Generalized Wilcoxon test
Comparison: Coughp-value: 0.0001Generalized Wilcoxon test
Comparison: Sore throatp-value: 0.0298Generalized Wilcoxon test
Comparison: Headachep-value: 0.0297Generalized Wilcoxon test
Comparison: Feverishness or chillsp-value: 0.0003Generalized Wilcoxon test
Comparison: Muscle or joint painp-value: 0.0094Generalized Wilcoxon test
Comparison: Fatiguep-value: 0.0007Generalized Wilcoxon test
Secondary
Time to Alleviation of the Four Systemic Symptoms in Adults Randomized to Baloxavir or Oseltamivir
Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of the 4 systemic symptoms was defined as the time between the initiation of the study treatment to the time when all 4 systemic symptoms (headache, feverishness or chills, muscle or joint pain, and fatigue) were assessed by the participant as 0 (None) or 1 (Mild) for a duration of at least 21.5 hours. Time to alleviation of the 4 systemic symptoms was analyzed using KM methods; participants who did not experience alleviation of symptoms were censored at the last observation time point.
Time frame: Initiation of study treatment up to Day 14
Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, with available time to alleviation of the 4 systemic symptoms data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baloxavir | Time to Alleviation of the Four Systemic Symptoms in Adults Randomized to Baloxavir or Oseltamivir | 36.7 hours |
| Placebo | Time to Alleviation of the Four Systemic Symptoms in Adults Randomized to Baloxavir or Oseltamivir | 37.4 hours |
p-value: 0.4194Generalized Wilcoxon test
Secondary
Time to Alleviation of the Four Systemic Symptoms in Participants Randomized to Baloxavir or Placebo
Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of the 4 systemic symptoms was defined as the time between the initiation of the study treatment to the time when all 4 systemic symptoms (headache, feverishness or chills, muscle or joint pain, and fatigue) were assessed by the participant as 0 (None) or 1 (Mild) for a duration of at least 21.5 hours. Time to alleviation of the 4 systemic symptoms was analyzed using KM methods; participants who did not experience alleviation of symptoms were censored at the last observation time point.
Time frame: Initiation of study treatment up to Day 14
Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo with available time to alleviation of the 4 systemic symptoms data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baloxavir | Time to Alleviation of the Four Systemic Symptoms in Participants Randomized to Baloxavir or Placebo | 33.8 hours |
| Placebo | Time to Alleviation of the Four Systemic Symptoms in Participants Randomized to Baloxavir or Placebo | 53.5 hours |
p-value: <0.0001Generalized Wilcoxon test
Secondary
Time to Alleviation of the Three Respiratory Symptoms in Adults Randomized to Baloxavir or Oseltamivir
Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of the 3 respiratory symptoms was defined as the time from the start of study treatment to the time when all 3 respiratory symptoms (cough, sore throat and nasal congestion) were assessed by the participant as absent (0) or mild (1) for at least 21.5 hours. Time to alleviation of the 3 respiratory symptoms was analyzed using the KM method; participants who did not experience alleviation of symptoms were censored at the last observation time point.
Time frame: Initiation of study treatment up to Day 14
Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, with available time to alleviation of the 3 respiratory symptoms data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baloxavir | Time to Alleviation of the Three Respiratory Symptoms in Adults Randomized to Baloxavir or Oseltamivir | 46.0 hours |
| Placebo | Time to Alleviation of the Three Respiratory Symptoms in Adults Randomized to Baloxavir or Oseltamivir | 44.6 hours |
p-value: 0.4856Generalized Wilcoxon test
Secondary
Time to Alleviation of the Three Respiratory Symptoms in Participants Randomized to Baloxavir or Placebo
Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of the 3 respiratory symptoms was defined as the time from the start of study treatment to the time when all 3 respiratory symptoms (cough, sore throat and nasal congestion) were assessed by the participant as absent (0) or mild (1) for at least 21.5 hours. Time to alleviation of the 3 respiratory symptoms was analyzed using the KM method; participants who did not experience alleviation of symptoms were censored at the last observation time point.
Time frame: Initiation of study treatment up to Day 14
Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo with available time to alleviation of the 3 respiratory symptoms data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baloxavir | Time to Alleviation of the Three Respiratory Symptoms in Participants Randomized to Baloxavir or Placebo | 46.0 hours |
| Placebo | Time to Alleviation of the Three Respiratory Symptoms in Participants Randomized to Baloxavir or Placebo | 69.1 hours |
p-value: <0.0001Generalized Wilcoxon test
Secondary
Time to Cessation of Viral Shedding Determined by Virus RNA in Adults Randomized to Baloxavir or Oseltamivir
Time to cessation of viral shedding by RT-PCR was defined as the time between the initiation of the study treatment and first time when the virus RNA was below the limit of detection measured by RT-PCR. Time to cessation of viral shedding by RT-PCR was analyzed using the KM method; participants whose virus RNA had not reached cessation by the last observation time point were treated as censored at that time point.
Time frame: Day 1 to Day 9
Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, with positive influenza virus RNA determined by RT-PCR on Day 1 whose time to cessation of viral shedding by RTPCR was not missing were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baloxavir | Time to Cessation of Viral Shedding Determined by Virus RNA in Adults Randomized to Baloxavir or Oseltamivir | 216.0 hours |
| Placebo | Time to Cessation of Viral Shedding Determined by Virus RNA in Adults Randomized to Baloxavir or Oseltamivir | 240.0 hours |
p-value: 0.010295% CI: [-48, 24]Generalized Wilcoxon test
Secondary
Time to Cessation of Viral Shedding Determined by Virus RNA in Participants Randomized to Baloxavir or Placebo
Time to cessation of viral shedding by RT-PCR was defined as the time between the initiation of the study treatment and first time when the virus RNA was below the limit of detection measured by RT-PCR. Time to cessation of viral shedding by RT-PCR was analyzed using the KM method; participants whose virus RNA had not reached cessation by the last observation time point were treated as censored at that time point.
Time frame: Day 1 to Day 9
Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo, with positive influenza virus RNA determined by RT-PCR on Day 1 whose time to cessation of viral shedding by RTPCR was not missing were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baloxavir | Time to Cessation of Viral Shedding Determined by Virus RNA in Participants Randomized to Baloxavir or Placebo | 216.0 hours |
| Placebo | Time to Cessation of Viral Shedding Determined by Virus RNA in Participants Randomized to Baloxavir or Placebo | 240.0 hours |
p-value: 0.00295% CI: [-120, 0]Generalized Wilcoxon test
Secondary
Time to Cessation of Viral Shedding Determined by Virus Titer in Adults Randomized to Baloxavir or Oseltamivir
Time to cessation of viral shedding by virus titer was defined as the time between the initiation of the study treatment and first time when the virus titer was below the limit of detection (0.7 log₁₀\[TCID₅₀/mL\]). The time to cessation of viral shedding determined by virus titer was analyzed using the Kaplan-Meier (KM) method; participants whose virus titer had not reached cessation by the last observation time point were treated as censored at that time point.
Time frame: Day 1 to Day 9
Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, with a positive virus titer on Day 1 whose time to cessation of viral shedding by virus titer was not missing..
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baloxavir | Time to Cessation of Viral Shedding Determined by Virus Titer in Adults Randomized to Baloxavir or Oseltamivir | 24.0 hours |
| Placebo | Time to Cessation of Viral Shedding Determined by Virus Titer in Adults Randomized to Baloxavir or Oseltamivir | 72.0 hours |
p-value: <0.000195% CI: [-72, -24]Generalized Wilcoxon test
Secondary
Time to Cessation of Viral Shedding Determined by Virus Titer in Participants Randomized to Baloxavir or Placebo
Time to cessation of viral shedding by virus titer was defined as the time between the initiation of the study treatment and first time when the virus titer was below the limit of detection (0.7 log₁₀\[TCID₅₀/mL\]). The median and 95% confidence interval (CI) for time to cessation of viral shedding determined by virus titer was analyzed using the Kaplan-Meier (KM) method; participants whose virus titer had not reached cessation by the last observation time point were treated as censored at that time point.
Time frame: Day 1 to Day 9
Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo with a positive virus titer on Day 1 whose time to cessation of viral shedding by virus titer was not missing were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baloxavir | Time to Cessation of Viral Shedding Determined by Virus Titer in Participants Randomized to Baloxavir or Placebo | 24.0 hours |
| Placebo | Time to Cessation of Viral Shedding Determined by Virus Titer in Participants Randomized to Baloxavir or Placebo | 96.0 hours |
p-value: <0.000195% CI: [-72, -48]Generalized Wilcoxon test
Secondary
Time to Resolution of Fever in Adults Randomized to Baloxavir or Oseltamivir
Time to resolution of fever was defined as the time between the initiation of the study treatment and the resolution of fever. The resolution of fever was defined as the time when the participant's self-measured axillary temperature became less than 37ºC and was maintained at less than 37ºC for a duration of at least 12 hours. Time to resolution of fever was analyzed using KM methods; participants who did not experience resolution of fever by the last observation time point were censored at that time point.
Time frame: Initiation of study treatment up to Day 14
Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, whose body temperature at baseline was more than 37°C and time to resolution of fever was not missing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baloxavir | Time to Resolution of Fever in Adults Randomized to Baloxavir or Oseltamivir | 24.4 hours |
| Placebo | Time to Resolution of Fever in Adults Randomized to Baloxavir or Oseltamivir | 24.0 hours |
p-value: 0.9225Generalized Wilcoxon test
Secondary
Time to Resolution of Fever in Participants Randomized to Baloxavir or Placebo
Time to resolution of fever was defined as the time between the initiation of the study treatment and the resolution of fever. The resolution of fever was defined as the time when the participant's self-measured axillary temperature became less than 37ºC and was maintained at less than 37ºC for a duration of at least 12 hours. Time to resolution of fever was analyzed using KM methods; participants who did not experience resolution of fever by the last observation time point were censored at that time point.
Time frame: Initiation of study treatment up to Day 14
Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo whose body temperature at baseline was more than 37°C and time to resolution of fever was not missing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baloxavir | Time to Resolution of Fever in Participants Randomized to Baloxavir or Placebo | 24.5 hours |
| Placebo | Time to Resolution of Fever in Participants Randomized to Baloxavir or Placebo | 42.0 hours |
p-value: <0.000195% CI: [-21.1, -11.9]Generalized Wilcoxon test
Secondary
Time to Return to Preinfluenza Health Status in Adults Randomized to Baloxavir or Oseltamivir
Participants were asked to record their preinfluenza health status on a scale from 0 (worst possible health) to 10 (normal health \[for someone your age and your health condition\]), and their health status every day after initiation of study treatment on the same scale. Return to preinfluenza health status was defined as time from the initiation of the study treatment to the first time when the health status score was equal to or higher than the preinfluenza health status score. Time to return to preinfluenza health status was analyzed using KM methods; participants with a smaller number on the scale for health status by the last observation time point were censored at that time point.
Time frame: Initiation of study treatment up to Day 14
Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, whose health status score at baseline was lower than the preinfluenza health status score and with available time to return to preinfluenza health status data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baloxavir | Time to Return to Preinfluenza Health Status in Adults Randomized to Baloxavir or Oseltamivir | 127.8 hours |
| Placebo | Time to Return to Preinfluenza Health Status in Adults Randomized to Baloxavir or Oseltamivir | 128.5 hours |
p-value: 0.7176Generalized Wilcoxon test
Secondary
Time to Return to Preinfluenza Health Status in Participants Randomized to Baloxavir or Placebo
Participants were asked to record their preinfluenza health status on a scale from 0 (worst possible health) to 10 (normal health \[for someone your age and your health condition\]), and their health status every day after initiation of study treatment on the same scale. Return to preinfluenza health status was defined as time from the initiation of the study treatment to the first time when the health status score was equal to or higher than the preinfluenza health status score. Time to return to preinfluenza health status was analyzed using KM methods; participants with a smaller number on the scale for health status by the last observation time point were censored at that time point.
Time frame: Initiation of study treatment up to Day 14
Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo whose health status score at baseline was lower than the preinfluenza health status score and with available time to return to preinfluenza health status data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baloxavir | Time to Return to Preinfluenza Health Status in Participants Randomized to Baloxavir or Placebo | 129.2 hours |
| Placebo | Time to Return to Preinfluenza Health Status in Participants Randomized to Baloxavir or Placebo | 168.8 hours |
p-value: 0.0563Generalized Wilcoxon test