CAPSTONE 1: A Study of S-033188 (Baloxavir Marboxil) Compared With Placebo or Oseltamivir in Otherwise Healthy Patients With Influenza
Sponsor
Shionogi (Industry)
Overall Status
Completed
CT.gov ID
NCT02954354
Collaborator
(none)
1,436
5
4.5
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
1436 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Multicenter, Randomized, Double-blind Study of a Single Dose of S-033188 (Baloxavir Marboxil) Compared With Placebo or Oseltamivir 75 mg Twice Daily for 5 Days in Otherwise Healthy Patients With Influenza
Actual Study Start Date
:
Dec 8, 2016
Actual Primary Completion Date
:
Apr 4, 2017
Actual Study Completion Date
:
Apr 24, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Adults: Baloxavir Marboxil Participants aged 20 to 64 years will receive two or four 20 mg baloxavir marboxil tablets orally on Day 1 and one oseltamivir placebo capsule orally twice a day (BID) on Days 1 to 5. |
Drug: Baloxavir Marboxil
2 to4 X 20-mg tablets taken orally
Other Names:
Drug: Placebo to Oseltamivir
Placebo capsules matching oseltamivir 75 mg capsules
|
| Active Comparator: Adults: Oseltamivir Participants aged 20 to 64 years will receive 75 mg oseltamivir twice a day on Days 1 to 5 and two or four baloxavir marboxil placebo tablets on Day 1. |
Drug: Placebo to Baloxavir Marboxil
2 to4 X 20-mg tablets taken orally
Drug: Oseltamivir
75 mg capsules taken orally
Other Names:
|
| Placebo Comparator: Adults: Placebo Participants aged 20 to 64 years will receive two or four baloxavir marboxil placebo tablets on Day 1 and one oseltamivir placebo capsule orally twice a day on Days 1 to 5. |
Drug: Placebo to Baloxavir Marboxil
2 to4 X 20-mg tablets taken orally
Drug: Placebo to Oseltamivir
Placebo capsules matching oseltamivir 75 mg capsules
|
| Experimental: Adolescents: Baloxavir Marboxil Participants aged 12 to 19 years will receive two or four baloxavir marboxil 20 mg tablets on Day 1. |
Drug: Baloxavir Marboxil
2 to4 X 20-mg tablets taken orally
Other Names:
|
| Placebo Comparator: Adolescents: Placebo Participants aged 12 to 19 years will receive two or four baloxavir marboxil placebo tablets on Day 1. |
Drug: Placebo to Baloxavir Marboxil
2 to4 X 20-mg tablets taken orally
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
- 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) .
- 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.
- 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.
- 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.
- 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]
Eligibility Criteria
Criteria
Ages Eligible for Study:
12 Years
to 64 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
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
-
Male or female patients aged ≥ 12 to ≤ 64 years at the time of signing the informed consent/assent form.
-
Patients with a diagnosis of influenza virus infection confirmed by all of the following:
-
Fever ≥ 38ºC (axillary) in the predose examinations or > 4 hours after dosing of antipyretics if they were taken
-
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
- 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
-
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:
-
Time of the first increase in body temperature (an increase of at least 1ºC from normal body temperature)
-
Time when the patient experiences at least one general or respiratory symptom
-
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:
-
Patients with severe influenza virus infection requiring inpatient treatment.
-
Patients aged ≥ 20 years with known allergy to oseltamivir (Tamiflu®).
-
Patients with any of the following risk factors
-
Women who are pregnant or within 2 weeks post-partum
-
Residents of long-term care facilities (eg, welfare facilities for the elderly, nursing homes)
-
Chronic respiratory diseases including bronchial asthma
-
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)
-
Heart disease (such as congenital heart disease, congestive heart failure, or coronary artery disease), excluding hypertension without any other heart-related symptoms)
-
American Indians and Alaskan natives
-
Blood disorders (such as sickle cell disease)
-
Endocrine disorders (including diabetes mellitus)
-
Kidney disorders
-
Liver disorders
-
Metabolic disorders
-
Compromised immune system (including patients receiving immunosuppressant therapy, or those with cancer or human immunodeficiency virus [HIV] infection)
-
Morbid obesity (body mass index [BMI] ≥ 40)
-
Patients unable to swallow tablets or capsules.
-
Patients who have previously received Baloxavir Marboxil.
-
Patients weighing < 40 kg
-
Patients who have been exposed to an investigational drug within 30 days prior to the predose examinations.
-
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:
-
Postmenopausal (defined as cessation of regular menstrual periods for 2 years or more and confirmed by a follicle-stimulating hormone test) women
-
Women who are surgically sterile by hysterectomy, bilateral oophorectomy, or tubal ligation
-
Patients with concurrent infections requiring systemic antimicrobial and/or antiviral therapy at the predose examinations.
-
Patients who have received peramivir, laninamivir, oseltamivir, zanamivir, rimantadine, umifenovir, or amantadine within 30 days prior to the predose examinations.
-
Patients who have received an investigational monoclonal antibody for a viral disease in the last year.
-
Patients with severe underlying diseases.
-
Patients with known creatinine clearance ≤ 60 mL/min.
-
Patients who, in the opinion of the investigator, would be unlikely to comply with required study visits, self-assessments, and interventions
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Shionogi
Investigators
- Study Director: Clinical Support Help Line Shionogi Clinical Trials Administrator, Shionogi
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Shionogi
ClinicalTrials.gov Identifier:
NCT02954354
Other Study ID Numbers:
- 1601T0831
First Posted:
Nov 3, 2016
Last Update Posted:
May 8, 2019
Last Verified:
Apr 1, 2019
Keywords provided by Shionogi
Additional relevant MeSH terms:
Study Results
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 Detail | 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. |
| Arm/Group Title | Baloxavir | Placebo | Oseltamivir |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Period Title: Overall Study | |||
| STARTED | 612 | 310 | 514 |
| Received Study Drug | 610 | 309 | 513 |
| Intention to Treat Infected Population | 456 | 231 | 377 |
| COMPLETED | 578 | 290 | 498 |
| NOT COMPLETED | 34 | 20 | 16 |
Baseline Characteristics
| Arm/Group Title | Baloxavir | Placebo | Oseltamivir | Total |
|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. | Total of all reporting groups |
| Overall Participants | 456 | 231 | 377 | 1064 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
33.5
(13.5)
|
33.9
(13.7)
|
36.0
(11.8)
|
34.5
(13.0)
|
| Age, Customized (Count of Participants) | ||||
| ≥ 12 to ≤ 19 years |
80
17.5%
|
38
16.5%
|
0
0%
|
118
11.1%
|
| ≥ 20 to ≤ 29 years |
121
26.5%
|
61
26.4%
|
134
35.5%
|
316
29.7%
|
| ≥ 30 to ≤ 39 years |
92
20.2%
|
47
20.3%
|
104
27.6%
|
243
22.8%
|
| ≥ 40 to ≤ 49 years |
97
21.3%
|
48
20.8%
|
77
20.4%
|
222
20.9%
|
| ≥ 50 to ≤ 59 years |
52
11.4%
|
30
13%
|
51
13.5%
|
133
12.5%
|
| ≥ 60 to ≤ 64 years |
14
3.1%
|
7
3%
|
11
2.9%
|
32
3%
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
224
49.1%
|
111
48.1%
|
159
42.2%
|
494
46.4%
|
| Male |
232
50.9%
|
120
51.9%
|
218
57.8%
|
570
53.6%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
32
7%
|
11
4.8%
|
25
6.6%
|
68
6.4%
|
| Not Hispanic or Latino |
424
93%
|
220
95.2%
|
352
93.4%
|
996
93.6%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
349
76.5%
|
178
77.1%
|
305
80.9%
|
832
78.2%
|
| Black or African American |
18
3.9%
|
11
4.8%
|
9
2.4%
|
38
3.6%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
1
0.3%
|
1
0.1%
|
| White |
85
18.6%
|
40
17.3%
|
60
15.9%
|
185
17.4%
|
| Other |
4
0.9%
|
2
0.9%
|
2
0.5%
|
8
0.8%
|
| Time From Symptom Onset to Initiation of the Trial Regimen (Count of Participants) | ||||
| ≥ 0 to ≤ 12 hours |
60
13.2%
|
34
14.7%
|
41
10.9%
|
135
12.7%
|
| > 12 to ≤ 24 hours |
178
39%
|
87
37.7%
|
163
43.2%
|
428
40.2%
|
| > 24 to ≤ 36 hours |
139
30.5%
|
67
29%
|
94
24.9%
|
300
28.2%
|
| > 36 to ≤ 48 hours |
79
17.3%
|
43
18.6%
|
79
21%
|
201
18.9%
|
| Influenza Virus Type or Subtype on RT-PCR Assay at Enrollment (Count of Participants) | ||||
| A/H1N1pdm |
7
1.5%
|
7
3%
|
2
0.5%
|
16
1.5%
|
| A/H3 |
393
86.2%
|
196
84.8%
|
332
88.1%
|
921
86.6%
|
| B |
38
8.3%
|
20
8.7%
|
34
9%
|
92
8.6%
|
| Mixed infection |
8
1.8%
|
3
1.3%
|
6
1.6%
|
17
1.6%
|
| Other |
10
2.2%
|
5
2.2%
|
3
0.8%
|
18
1.7%
|
| Region (Count of Participants) | ||||
| Japan/Asia |
343
75.2%
|
175
75.8%
|
303
80.4%
|
821
77.2%
|
| Rest of the world |
113
24.8%
|
56
24.2%
|
74
19.6%
|
243
22.8%
|
| Composite Symptom Score (Count of Participants) | ||||
| ≤ 11 |
144
31.6%
|
72
31.2%
|
119
31.6%
|
335
31.5%
|
| ≥ 12 |
312
68.4%
|
159
68.8%
|
258
68.4%
|
729
68.5%
|
Outcome Measures
| Title | Time to Alleviation of Symptoms in Participants Randomized to Baloxavir or Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the intention-to-treat infection population assigned to baloxavir or placebo with available time to alleviation of symptoms data. |
| Arm/Group Title | Baloxavir | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 455 | 230 |
| Median (95% Confidence Interval) [hours] |
53.7
|
80.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Adjusted p-value, two-sided significance level of 0.05 | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -26.5 | |
| Confidence Interval |
(2-Sided) 95% -35.8 to -17.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Analysis using the stratified log rank test was performed as a sensitivity analysis. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Log Rank | |
| Comments | Log rank test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Title | Time to Alleviation of Symptoms in Adults Randomized to Baloxavir or Oseltamivir |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Oseltamivir |
|---|---|---|
| Arm/Group Description | 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 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Measure Participants | 375 | 377 |
| Median (95% Confidence Interval) [hours] |
53.5
|
53.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7560 |
| Comments | Adjusted p-value, two-sided significance level of 0.05 | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -6.6 to 6.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Analysis using the stratified log rank test was performed as a sensitivity analysis. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3761 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Log Rank | |
| Comments | Log rank test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Title | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 427 | 210 |
| Day 2 |
47.6
10.4%
|
96.0
41.6%
|
| Day 3 |
21.7
4.8%
|
70.5
30.5%
|
| Day 4 |
16.7
3.7%
|
56.1
24.3%
|
| Day 5 |
13.5
3%
|
29.7
12.9%
|
| Day 6 |
8.2
1.8%
|
12.5
5.4%
|
| Day 9 |
2.9
0.6%
|
4.6
2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 3 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 5 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 6 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4767 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 9 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3353 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Title | Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Oseltamivir |
|---|---|---|
| Arm/Group Description | 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 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Measure Participants | 352 | 359 |
| Day 2 |
47.4
10.4%
|
91.1
39.4%
|
| Day 3 |
20.0
4.4%
|
57.3
24.8%
|
| Day 4 |
16.1
3.5%
|
27.6
11.9%
|
| Day 5 |
12.9
2.8%
|
20.8
9%
|
| Day 6 |
5.6
1.2%
|
9.0
3.9%
|
| Day 9 |
3.0
0.7%
|
3.2
1.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 3 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0852 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 5 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0063 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 6 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6187 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 9 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8637 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | ||
| Title | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 456 | 231 |
| Day 2 |
97.3
21.3%
|
97.7
42.3%
|
| Day 3 |
95.6
21%
|
97.2
42.1%
|
| Day 4 |
93.4
20.5%
|
91.0
39.4%
|
| Day 5 |
87.4
19.2%
|
93.9
40.6%
|
| Day 6 |
74.8
16.4%
|
77.2
33.4%
|
| Day 9 |
61.5
13.5%
|
72.4
31.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6145 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 3 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2505 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4190 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 5 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0095 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 6 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7393 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 9 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0049 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Title | Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Oseltamivir |
|---|---|---|
| Arm/Group Description | 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 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Measure Participants | 376 | 377 |
| Day 2 |
97.3
21.3%
|
98.6
42.7%
|
| Day 3 |
95.3
20.9%
|
97.5
42.2%
|
| Day 4 |
93.6
20.5%
|
93.0
40.3%
|
| Day 5 |
86.6
19%
|
92.1
39.9%
|
| Day 6 |
69.3
15.2%
|
80.7
34.9%
|
| Day 9 |
60.2
13.2%
|
64.7
28%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2266 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 3 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1379 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5479 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 5 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0241 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 6 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0898 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 9 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2548 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Title | Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 427 | 210 |
| Day 2 |
-4.45
(2.03)
|
-1.19
(2.43)
|
| Day 3 |
-4.82
(1.99)
|
-2.88
(2.88)
|
| Day 4 |
-4.50
(2.02)
|
-3.31
(2.34)
|
| Day 5 |
-4.95
(1.93)
|
-4.47
(2.21)
|
| Day 6 |
-4.58
(1.99)
|
-4.68
(2.12)
|
| Day 9 |
-5.06
(1.87)
|
-4.87
(1.85)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 3 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0008 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 5 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0132 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 6 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9307 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 9 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1677 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Title | Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Oseltamivir |
|---|---|---|
| Arm/Group Description | 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 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Measure Participants | 352 | 359 |
| Day 2 |
-4.39
(2.07)
|
-2.53
(2.03)
|
| Day 3 |
-4.79
(2.03)
|
-4.20
(2.02)
|
| Day 4 |
-4.46
(2.03)
|
-4.63
(1.89)
|
| Day 5 |
-4.95
(1.94)
|
-4.98
(1.81)
|
| Day 6 |
-4.56
(1.99)
|
-4.85
(1.95)
|
| Day 9 |
-5.03
(1.89)
|
-5.22
(1.70)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 3 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8010 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 5 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9451 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 6 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2256 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 9 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3332 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Title | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 456 | 231 |
| Day 2 |
-1.63
(1.03)
|
-0.56
(1.37)
|
| Day 3 |
-2.80
(1.20)
|
-1.61
(1.76)
|
| Day 4 |
-3.07
(1.59)
|
-1.95
(1.76)
|
| Day 5 |
-3.75
(1.47)
|
-3.04
(1.62)
|
| Day 6 |
-3.83
(1.64)
|
-3.03
(1.85)
|
| Day 9 |
-4.43
(1.42)
|
-4.06
(1.47)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 3 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 5 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 6 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0010 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 9 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Title | Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Oseltamivir |
|---|---|---|
| Arm/Group Description | 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 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Measure Participants | 376 | 377 |
| Day 2 |
-1.61
(1.06)
|
-1.10
(1.10)
|
| Day 3 |
-2.79
(1.21)
|
-2.44
(1.24)
|
| Day 4 |
-2.94
(1.62)
|
-2.97
(1.29)
|
| Day 5 |
-3.76
(1.44)
|
-3.62
(1.34)
|
| Day 6 |
-3.81
(1.52)
|
-3.88
(1.35)
|
| Day 9 |
-4.43
(1.43)
|
-4.52
(1.22)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 3 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 4 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4148 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 5 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0338 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 6 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9619 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Day 9 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8491 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Title | Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Participants Randomized to Baloxavir or Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 408 | 197 |
| Mean (Standard Deviation) [log₁₀[TCID₅₀/mL]*hours] |
-836.2
(348.9)
|
-641.8
(377.6)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Title | Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Adults Randomized to Baloxavir or Oseltamivir |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Oseltamivir |
|---|---|---|
| Arm/Group Description | 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 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Measure Participants | 336 | 340 |
| Mean (Standard Deviation) [log₁₀[TCID₅₀/mL]*hours] |
-829.6
(350.3)
|
-790.2
(328.4)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0313 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Title | Area Under the Curve (AUC) Adjusted by Baseline of Influenza Virus RNA in Participants Randomized to Baloxavir or Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 426 | 208 |
| Mean (Standard Deviation) [log₁₀ virus particles/mL*hours] |
-582.0
(230.9)
|
-456.8
(269.6)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Title | Area Under the Curve (AUC) Adjusted by Baseline of Influenza Virus RNA in Adults Randomized to Baloxavir or Oseltamivir |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Oseltamivir |
|---|---|---|
| Arm/Group Description | 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 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Measure Participants | 351 | 349 |
| Mean (Standard Deviation) [log₁₀ virus particles/mL*hours] |
-581.0
(231.2)
|
-569.7
(228.8)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2424 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | van Elteren test | |
| Comments | Van Elteren test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Title | Time to Cessation of Viral Shedding Determined by Virus Titer in Participants Randomized to Baloxavir or Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 426 | 209 |
| Median (95% Confidence Interval) [hours] |
24.0
|
96.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -72.0 | |
| Confidence Interval |
(2-Sided) 95% -72.0 to -48.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Cessation of Viral Shedding Determined by Virus Titer in Adults Randomized to Baloxavir or Oseltamivir |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Oseltamivir |
|---|---|---|
| Arm/Group Description | 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 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Measure Participants | 351 | 357 |
| Median (95% Confidence Interval) [hours] |
24.0
|
72.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -48.0 | |
| Confidence Interval |
(2-Sided) 95% -72.0 to -24.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Cessation of Viral Shedding Determined by Virus RNA in Participants Randomized to Baloxavir or Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 455 | 230 |
| Median (95% Confidence Interval) [hours] |
216.0
|
240.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0020 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -24.0 | |
| Confidence Interval |
(2-Sided) 95% -120.0 to 0.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Cessation of Viral Shedding Determined by Virus RNA in Adults Randomized to Baloxavir or Oseltamivir |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Oseltamivir |
|---|---|---|
| Arm/Group Description | 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 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Measure Participants | 375 | 375 |
| Median (95% Confidence Interval) [hours] |
216.0
|
240.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0102 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -24.0 | |
| Confidence Interval |
(2-Sided) 95% -48.0 to 24.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the intention-to-treat infection population assigned to baloxavir or placebo with available alleviation of symptoms data at each time point. |
| Arm/Group Title | Baloxavir | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 456 | 231 |
| 12 hours |
9.7
2.1%
|
8.1
3.5%
|
| 24 hours |
23.1
5.1%
|
12.8
5.5%
|
| 36 hours |
42.4
9.3%
|
23.1
10%
|
| 48 hours |
50.7
11.1%
|
26.4
11.4%
|
| 72 hours |
68.9
15.1%
|
49.5
21.4%
|
| 96 hours |
78.6
17.2%
|
69.9
30.3%
|
| 120 hours |
85.5
18.8%
|
81.6
35.3%
|
| 144 hours |
89.1
19.5%
|
85.4
37%
|
| 168 hours |
91.6
20.1%
|
88.3
38.2%
|
| 192 hours |
90.9
19.9%
|
91.4
39.6%
|
| 216 hours |
91.1
20%
|
91.9
39.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 12 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5973 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 24 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0010 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 36 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 48 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 72 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 96 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0115 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 120 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1298 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 144 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1170 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 168 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0757 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 192 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9453 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 216 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8657 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Title | Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Oseltamivir |
|---|---|---|
| Arm/Group Description | 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 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Measure Participants | 376 | 377 |
| 12 hours |
8.7
1.9%
|
4.9
2.1%
|
| 24 hours |
21.3
4.7%
|
22.7
9.8%
|
| 36 hours |
41.1
9%
|
38.7
16.8%
|
| 48 hours |
51.0
11.2%
|
54.4
23.5%
|
| 72 hours |
70.7
15.5%
|
73.0
31.6%
|
| 96 hours |
79.8
17.5%
|
80.5
34.8%
|
| 120 hours |
86.1
18.9%
|
87.0
37.7%
|
| 144 hours |
89.2
19.6%
|
91.3
39.5%
|
| 168 hours |
91.4
20%
|
94.3
40.8%
|
| 192 hours |
90.8
19.9%
|
95.5
41.3%
|
| 216 hours |
90.9
19.9%
|
96.3
41.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 12 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0458 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 24 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7565 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 36 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3297 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 48 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4442 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 72 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6029 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 96 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9881 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 120 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9257 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 144 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5317 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 168 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2144 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 192 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0413 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 216 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0409 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Title | Time to Alleviation of the Four Systemic Symptoms in Participants Randomized to Baloxavir or Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 455 | 230 |
| Median (95% Confidence Interval) [hours] |
33.8
|
53.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -19.8 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Alleviation of the Four Systemic Symptoms in Adults Randomized to Baloxavir or Oseltamivir |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Oseltamivir |
|---|---|---|
| Arm/Group Description | 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 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Measure Participants | 375 | 377 |
| Median (95% Confidence Interval) [hours] |
36.7
|
37.4
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4194 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -0.7 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Alleviation of the Three Respiratory Symptoms in Participants Randomized to Baloxavir or Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 455 | 230 |
| Median (95% Confidence Interval) [hours] |
46.0
|
69.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -23.1 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Alleviation of the Three Respiratory Symptoms in Adults Randomized to Baloxavir or Oseltamivir |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Oseltamivir |
|---|---|---|
| Arm/Group Description | 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 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Measure Participants | 375 | 377 |
| Median (95% Confidence Interval) [hours] |
46.0
|
44.6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4856 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | 1.3 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 456 | 231 |
| 12 hours |
-2.4
(0.2)
|
-2.5
(0.3)
|
| 24 hours |
-4.7
(0.2)
|
-3.6
(0.3)
|
| 36 hours |
-6.7
(0.2)
|
-4.9
(0.3)
|
| 48 hours |
-7.8
(0.2)
|
-6.0
(0.3)
|
| 72 hours |
-9.4
(0.2)
|
-8.0
(0.2)
|
| 96 hours |
-10.5
(0.2)
|
-9.5
(0.2)
|
| 120 hours |
-10.9
(0.2)
|
-10.6
(0.2)
|
| 144 hours |
-11.6
(0.1)
|
-11.2
(0.2)
|
| 168 hours |
-11.9
(0.1)
|
-11.8
(0.2)
|
| 192 hours |
-12.0
(0.1)
|
-12.0
(0.2)
|
| 216 hours |
-12.4
(0.2)
|
-12.4
(0.3)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 12 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7173 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.5 to 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.3 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 24 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0009 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -1.1 | |
| Confidence Interval |
(2-Sided) 95% -1.7 to -0.4 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.3 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 36 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -1.8 | |
| Confidence Interval |
(2-Sided) 95% -2.4 to -1.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.3 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 48 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -1.8 | |
| Confidence Interval |
(2-Sided) 95% -2.4 to -1.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.3 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 72 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -1.4 | |
| Confidence Interval |
(2-Sided) 95% -2.0 to -0.9 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.3 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 96 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -1.0 | |
| Confidence Interval |
(2-Sided) 95% -1.5 to -0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.3 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 120 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1979 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.8 to 0.2 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 144 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1079 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.4 | |
| Confidence Interval |
(2-Sided) 95% -0.8 to 0.1 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 168 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5805 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 192 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8057 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2 |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 216 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9525 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.3 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Oseltamivir |
|---|---|---|
| Arm/Group Description | 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 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Measure Participants | 376 | 377 |
| 12 hours |
-2.2
(0.2)
|
-2.4
(0.2)
|
| 24 hours |
-4.5
(0.2)
|
-4.7
(0.2)
|
| 36 hours |
-6.5
(0.2)
|
-6.3
(0.2)
|
| 48 hours |
-7.6
(0.2)
|
-7.8
(0.2)
|
| 72 hours |
-9.6
(0.2)
|
-9.7
(0.2)
|
| 96 hours |
-10.5
(0.2)
|
-10.6
(0.2)
|
| 120 hours |
-11.0
(0.2)
|
-11.3
(0.2)
|
| 144 hours |
-11.8
(0.2)
|
-11.8
(0.2)
|
| 168 hours |
-11.9
(0.2)
|
-12.1
(0.2)
|
| 192 hours |
-12.0
(0.1)
|
-12.4
(0.2)
|
| 216 hours |
-12.4
(0.2)
|
-12.5
(0.2)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 12 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4091 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.3 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.3 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 24 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3073 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.3 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.3 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 36 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3465 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.8 to 0.3 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.3 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 48 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4285 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.3 to 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 72 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6703 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.4 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 96 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7187 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.3 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 120 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1350 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.3 | |
| Confidence Interval |
(2-Sided) 95% -0.1 to 0.7 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 144 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7046 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.3 to 0.5 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 168 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2765 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -0.2 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 192 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0274 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.4 | |
| Confidence Interval |
(2-Sided) 95% 0.0 to 0.8 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2 |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 216 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with baseline composite symptom score baseline (≤ 11 or ≥ 12)and region (Japan/Asia, Rest of the world) as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.1 | |
| Confidence Interval |
(2-Sided) 95% -0.3 to 0.6 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.2 |
|
| Estimation Comments | ||
| Title | Time to Resolution of Fever in Participants Randomized to Baloxavir or Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 448 | 230 |
| Median (95% Confidence Interval) [hours] |
24.5
|
42.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -17.5 | |
| Confidence Interval |
(2-Sided) 95% -21.1 to -11.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Resolution of Fever in Adults Randomized to Baloxavir or Oseltamivir |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Oseltamivir |
|---|---|---|
| Arm/Group Description | 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 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Measure Participants | 369 | 374 |
| Median (95% Confidence Interval) [hours] |
24.4
|
24.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9225 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Title | Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 449 | 230 |
| 12 hours |
26.5
5.8%
|
25.3
11%
|
| 24 hours |
64.3
14.1%
|
48.4
21%
|
| 36 hours |
80.8
17.7%
|
58.3
25.2%
|
| 48 hours |
89.3
19.6%
|
67.3
29.1%
|
| 72 hours |
93.7
20.5%
|
83.8
36.3%
|
| 96 hours |
92.8
20.4%
|
93.9
40.6%
|
| 120 hours |
92.9
20.4%
|
92.8
40.2%
|
| 144 hours |
93.4
20.5%
|
93.6
40.5%
|
| 168 hours |
93.3
20.5%
|
93.6
40.5%
|
| 192 hours |
94.1
20.6%
|
93.7
40.6%
|
| 216 hours |
92.5
20.3%
|
92.7
40.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 12 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7866 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 24 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 36 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 48 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 72 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 96 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7044 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 120 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8512 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 144 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8783 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 168 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8291 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 192 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8644 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 216 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9312 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Title | Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Oseltamivir |
|---|---|---|
| Arm/Group Description | 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 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Measure Participants | 370 | 374 |
| 12 hours |
25.0
5.5%
|
28.3
12.3%
|
| 24 hours |
64.3
14.1%
|
66.8
28.9%
|
| 36 hours |
81.9
18%
|
79.1
34.2%
|
| 48 hours |
90.1
19.8%
|
89.9
38.9%
|
| 72 hours |
93.8
20.6%
|
89.5
38.7%
|
| 96 hours |
93.9
20.6%
|
94.9
41.1%
|
| 120 hours |
93.8
20.6%
|
95.8
41.5%
|
| 144 hours |
92.8
20.4%
|
94.5
40.9%
|
| 168 hours |
93.6
20.5%
|
95.9
41.5%
|
| 192 hours |
94.6
20.7%
|
95.8
41.5%
|
| 216 hours |
92.8
20.4%
|
94.5
40.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 12 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2953 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 24 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5414 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 36 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2079 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 48 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7771 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world) | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 72 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0215 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 96 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8033 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world) | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 120 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4157 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 144 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5908 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world) | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 168 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2975 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 192 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8644 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 216 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5573 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05.m | |
| Method | Mantel Haenszel | |
| Comments | Mantel-Haenszel test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Title | Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the intention-to-treat infection population assigned to baloxavir or placebo with available temperature data at each time point. |
| Arm/Group Title | Baloxavir | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 456 | 231 |
| 12 hours |
37.40
(0.05)
|
37.49
(0.07)
|
| 24 hours |
36.73
(0.04)
|
37.07
(0.05)
|
| 36 hours |
36.49
(0.04)
|
36.90
(0.05)
|
| 48 hours |
36.32
(0.03)
|
36.69
(0.05)
|
| 72 hours |
36.26
(0.03)
|
36.48
(0.04)
|
| 96 hours |
36.27
(0.03)
|
36.31
(0.04)
|
| 120 hours |
36.28
(0.03)
|
36.25
(0.04)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 12 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2557 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | ANCOVA with baseline composite symptom score and region (Japan/Asia, Rest of the world) and body temperature at baseline as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.09 | |
| Confidence Interval |
(2-Sided) 95% -0.24 to 0.06 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.08 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 24 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | ANCOVA with baseline composite symptom score and region (Japan/Asia, Rest of the world) and body temperature at baseline as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.34 | |
| Confidence Interval |
(2-Sided) 95% -0.46 to -0.22 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.06 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 36 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | ANCOVA with baseline composite symptom score and region (Japan/Asia, Rest of the world) and body temperature at baseline as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.41 | |
| Confidence Interval |
(2-Sided) 95% -0.52 to -0.29 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.06 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 48 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | ANCOVA with baseline composite symptom score and region (Japan/Asia, Rest of the world) and body temperature at baseline as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.37 | |
| Confidence Interval |
(2-Sided) 95% -0.48 to -0.27 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.05 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 72 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | ANCOVA with baseline composite symptom score and region (Japan/Asia, Rest of the world) and body temperature at baseline as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.22 | |
| Confidence Interval |
(2-Sided) 95% -0.31 to -0.13 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.05 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 96 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4484 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | ANCOVA with baseline composite symptom score and region (Japan/Asia, Rest of the world) and body temperature at baseline as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Dfference |
| Estimated Value | -0.04 | |
| Confidence Interval |
(2-Sided) 95% -0.13 to 0.06 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.05 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | ANCOVA with baseline composite symptom score and region (Japan/Asia, Rest of the world) and body temperature at baseline as covariates. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5963 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | ANCOVA with baseline composite symptom score and region (Japan/Asia, Rest of the world) and body temperature at baseline as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.02 | |
| Confidence Interval |
(2-Sided) 95% -0.07 to 0.11 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.05 |
|
| Estimation Comments | ||
| Title | Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Oseltamivir |
|---|---|---|
| Arm/Group Description | 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 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Measure Participants | 376 | 377 |
| 12 hours |
37.47
(0.05)
|
37.35
(0.05)
|
| 24 hours |
36.78
(0.04)
|
36.73
(0.04)
|
| 36 hours |
36.55
(0.04)
|
36.54
(0.04)
|
| 48 hours |
36.34
(0.03)
|
36.36
(0.03)
|
| 72 hours |
36.30
(0.03)
|
36.31
(0.03)
|
| 96 hours |
36.26
(0.03)
|
36.23
(0.03)
|
| 120 hours |
36.27
(0.03)
|
36.21
(0.03)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 12 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0937 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | ANCOVA with baseline composite symptom score and region (Japan/Asia, Rest of the world) and body temperature at baseline as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.11 | |
| Confidence Interval |
(2-Sided) 95% -0.02 to 0.24 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.07 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 24 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3343 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | ANCOVA with baseline composite symptom score and region (Japan/Asia, Rest of the world) and body temperature at baseline as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.05 | |
| Confidence Interval |
(2-Sided) 95% -0.05 to 0.16 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.05 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 36 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9258 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | ANCOVA with baseline composite symptom score and region (Japan/Asia, Rest of the world) and body temperature at baseline as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.00 | |
| Confidence Interval |
(2-Sided) 95% -0.09 to 0.10 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.05 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 48 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6574 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | ANCOVA with baseline composite symptom score and region (Japan/Asia, Rest of the world) and body temperature at baseline as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.02 | |
| Confidence Interval |
(2-Sided) 95% -0.10 to 0.06 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.04 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 72 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8520 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | ANCOVA with baseline composite symptom score and region (Japan/Asia, Rest of the world) and body temperature at baseline as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.01 | |
| Confidence Interval |
(2-Sided) 95% -0.09 to 0.07 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.04 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 96 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4532 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | ANCOVA with baseline composite symptom score and region (Japan/Asia, Rest of the world) and body temperature at baseline as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.03 | |
| Confidence Interval |
(2-Sided) 95% -0.05 to 0.11 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.04 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | 120 hours | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1570 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | ANCOVA with baseline composite symptom score and region (Japan/Asia, Rest of the world) and body temperature at baseline as covariates. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.05 | |
| Confidence Interval |
(2-Sided) 95% -0.02 to 0.13 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.04 |
|
| Estimation Comments | ||
| Title | Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 455 | 230 |
| Cough |
38.3
|
61.4
|
| Sore Throat |
31.5
|
40.5
|
| Headache |
26.1
|
37.9
|
| Nasal Congestion |
31.8
|
52.5
|
| Feverishness or chills |
20.9
|
25.8
|
| Muscle or joint pain |
23.2
|
31.3
|
| Fatigue |
25.3
|
40.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Cough | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -23.1 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Sore throat | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0298 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -9.0 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Headache | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0297 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -11.8 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Nasal Congestion | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0027 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -20.7 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Feverishness or chills | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world) | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -4.9 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Muscle or joint pain | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0094 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -8.1 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Fatigue | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0007 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -15.3 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Oseltamivir |
|---|---|---|
| Arm/Group Description | 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 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Measure Participants | 375 | 377 |
| Cough |
38.2
|
31.4
|
| Sore Throat |
32.1
|
30.4
|
| Headache |
26.9
|
25.6
|
| Nasal Congestion |
33.0
|
31.3
|
| Feverishness or chills |
21.0
|
21.2
|
| Muscle or joint pain |
23.3
|
24.0
|
| Fatigue |
28.9
|
26.6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Cough | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6623 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | 6.8 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Sore throat | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8184 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | 1.8 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Headache | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9989 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | 1.3 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Nasal congestion | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3706 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | 1.7 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Feverishness or chills | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9973 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -0.1 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Muscle or joint pain | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6760 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -0.7 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Fatigue | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4241 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | 2.2 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Return to Preinfluenza Health Status in Participants Randomized to Baloxavir or Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 378 | 190 |
| Median (95% Confidence Interval) [hours] |
129.2
|
168.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Statistical Test of Hypothesis | p-Value | 0.0563 |
| Comments | ||
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -39.5 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Return to Preinfluenza Health Status in Adults Randomized to Baloxavir or Oseltamivir |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Baloxavir | Oseltamivir |
|---|---|---|
| Arm/Group Description | 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 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Measure Participants | 314 | 308 |
| Median (95% Confidence Interval) [hours] |
127.8
|
128.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7176 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Generalized Wilcoxon test | |
| Comments | Generalized Wilcoxon test stratified by composite symptom scores at baseline (≤ 11 or ≥ 12) and region (Japan/Asia or Rest of the world). | |
| Method of Estimation | Estimation Parameter | Difference |
| Estimated Value | -0.6 | |
| Confidence Interval |
() % to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the intention-to-treat infection population assigned to baloxavir or placebo |
| Arm/Group Title | Baloxavir | Placebo |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 456 | 231 |
| Any complication |
3.5
0.8%
|
4.3
1.9%
|
| Death |
0
0%
|
0
0%
|
| Hospitalization |
0
0%
|
0
0%
|
| Sinusitis |
0.9
0.2%
|
0.9
0.4%
|
| Otitis media |
0.4
0.1%
|
0
0%
|
| Bronchitis |
2.0
0.4%
|
3.5
1.5%
|
| Pneumonia |
0.4
0.1%
|
0.4
0.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Any Complications | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6728 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Fisher Exact | |
| Comments | ||
| Title | Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the intention-to-treat infection population ≥ 20 years of age and assigned to baloxavir or oseltamivir. |
| Arm/Group Title | Baloxavir | Oseltamivir |
|---|---|---|
| Arm/Group Description | 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 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Measure Participants | 376 | 377 |
| Any complication |
4.0
0.9%
|
2.4
1%
|
| Death |
0
0%
|
0
0%
|
| Hospitalization |
0
0%
|
0.3
0.1%
|
| Sinusitis |
0.8
0.2%
|
0
0%
|
| Otitis media |
0.5
0.1%
|
0.3
0.1%
|
| Bronchitis |
2.4
0.5%
|
1.6
0.7%
|
| Pneumonia |
0.5
0.1%
|
0.3
0.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Baloxavir, Placebo |
|---|---|---|
| Comments | Any Complications | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2217 |
| Comments | The p-value was not adjusted for multiplicity, testing was conducted at the two-sided significance level of 0.05. | |
| Method | Fisher Exact | |
| Comments | ||
| Title | Percentage of Participants With Adverse Events (AEs) |
|---|---|
| Description | |
| Time Frame | From first dose of study drug to Day 22 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study drug |
| Arm/Group Title | Baloxavir | Placebo | Oseltamivir |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. |
| Measure Participants | 610 | 309 | 513 |
| Adverse events (AEs) |
20.7
4.5%
|
24.6
10.6%
|
24.8
6.6%
|
| Serious adverse events (SAEs) |
0.3
0.1%
|
0.0
0%
|
0.0
0%
|
| AEs leading to withdrawal of study drug |
0.3
0.1%
|
0.3
0.1%
|
0.4
0.1%
|
| Treatment-related adverse events (TRAEs) |
4.4
1%
|
3.9
1.7%
|
8.4
2.2%
|
| Treatment-related serious adverse events |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| TRAEs leading to withdrawal of study drug |
0.0
0%
|
0.3
0.1%
|
0.2
0.1%
|
Adverse Events
| Time Frame | From first dose of treatment to Day 22 | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Baloxavir | Placebo | Oseltamivir | |||
| Arm/Group Description | 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. | 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. | Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1. | |||
All Cause Mortality |
||||||
| Baloxavir | Placebo | Oseltamivir | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/610 (0%) | 0/309 (0%) | 0/513 (0%) | |||
Serious Adverse Events |
||||||
| Baloxavir | Placebo | Oseltamivir | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/610 (0.3%) | 0/309 (0%) | 0/513 (0%) | |||
| Gastrointestinal disorders | ||||||
| Incarcerated inguinal hernia | 1/610 (0.2%) | 0/309 (0%) | 0/513 (0%) | |||
| Infections and infestations | ||||||
| Meningitis viral | 1/610 (0.2%) | 0/309 (0%) | 0/513 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Baloxavir | Placebo | Oseltamivir | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 47/610 (7.7%) | 40/309 (12.9%) | 45/513 (8.8%) | |||
| Gastrointestinal disorders | ||||||
| Diarrhoea | 18/610 (3%) | 14/309 (4.5%) | 11/513 (2.1%) | |||
| Nausea | 8/610 (1.3%) | 4/309 (1.3%) | 16/513 (3.1%) | |||
| Infections and infestations | ||||||
| Bronchitis | 16/610 (2.6%) | 17/309 (5.5%) | 18/513 (3.5%) | |||
| Sinusitis | 7/610 (1.1%) | 8/309 (2.6%) | 5/513 (1%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The sponsor can embargo results from a PI's center until the combined results from the completed study have been published in full or the sponsor confirms there will be no multicenter study publication. Results communications must be provided to the sponsor for review at least 60 days before submission for publication. By written request, the sponsor can extend the embargo up to an additional 60 days. The sponsor cannot require changes to scientific content and cannot further extend the embargo.
Results Point of Contact
| Name/Title | Shionogi Clinical Trials Administrator |
|---|---|
| Organization | Shionogi Inc. |
| Phone | 800-849-9707 |
| Shionogiclintrials-admin@shionogi.co.jp |
Responsible Party:
Shionogi
ClinicalTrials.gov Identifier:
NCT02954354
Other Study ID Numbers:
- 1601T0831
First Posted:
Nov 3, 2016
Last Update Posted:
May 8, 2019
Last Verified:
Apr 1, 2019