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A Study of S-033188 (Baloxavir Marboxil) Compared With Placebo or Oseltamivir in Otherwise Healthy Patients With Influenza (CAPSTONE 1)

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ClinicalTrials.gov Identifier: NCT02954354
Recruitment Status : Completed
First Posted : November 3, 2016
Results First Posted : December 14, 2018
Last Update Posted : December 14, 2018
Sponsor:
Information provided by (Responsible Party):
Shionogi Inc. ( Shionogi )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Influenza
Interventions Drug: Baloxavir Marboxil
Drug: Placebo to Baloxavir Marboxil
Drug: Oseltamivir
Drug: Placebo to Oseltamivir
Enrollment 1436
Recruitment Details This study was conducted at 297 sites, consisting of 141 sites in Japan, 149 sites in the United States, and 7 sites in Canada. Participants were enrolled from December 2016 to April 2017.
Pre-assignment Details

Participants 20 to 64 years of age were randomly assigned in a 2:2:1 ratio to receive a single oral dose of baloxavir, 75 mg oseltamivir twice daily for 5 days, or matching placebos.

Participants 12 to 19 years of age were randomly assigned in a 2:1 ratio to receive a single dose of either baloxavir or placebo.

Arm/Group Title Baloxavir Placebo Oseltamivir
Hide 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
Reason Not Completed
Adverse Event             2             2             4
Failure to Meet Eligibility Criteria             1             0             0
Lack of Efficacy             0             2             0
Withdrawal by Subject             17             9             11
Lost to Follow-up             12             5             0
Miscellaneous             2             2             1
Arm/Group Title Baloxavir Placebo Oseltamivir Total
Hide 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 Number of Baseline Participants 456 231 377 1064
Hide Baseline Analysis Population Description
Intention-to-treat infection (ITTI) population consisting of participants who received study drug with a confirmed diagnosis of influenza. Confirmation of influenza was based on the results of reverse transcription polymerase chain reaction (RT-PCR) on Day 1.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 456 participants 231 participants 377 participants 1064 participants
33.5  (13.5) 33.9  (13.7) 36.0  (11.8) 34.5  (13.0)
[1]
Measure Description: Note that the baloxavir and placebo groups included participants from 12 to 64 years of age whereas the oseltamivir group only included participants from 20 to 64 years of age.
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 456 participants 231 participants 377 participants 1064 participants
≥ 12 to ≤ 19 years
80
  17.5%
38
  16.5%
0
   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
  13.0%
51
  13.5%
133
  12.5%
≥ 60 to ≤ 64 years
14
   3.1%
7
   3.0%
11
   2.9%
32
   3.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 456 participants 231 participants 377 participants 1064 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)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 456 participants 231 participants 377 participants 1064 participants
Hispanic or Latino
32
   7.0%
11
   4.8%
25
   6.6%
68
   6.4%
Not Hispanic or Latino
424
  93.0%
220
  95.2%
352
  93.4%
996
  93.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 456 participants 231 participants 377 participants 1064 participants
American Indian or Alaska Native
0
   0.0%
0
   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
   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  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 456 participants 231 participants 377 participants 1064 participants
≥ 0 to ≤ 12 hours
60
  13.2%
34
  14.7%
41
  10.9%
135
  12.7%
> 12 to ≤ 24 hours
178
  39.0%
87
  37.7%
163
  43.2%
428
  40.2%
> 24 to ≤ 36 hours
139
  30.5%
67
  29.0%
94
  24.9%
300
  28.2%
> 36 to ≤ 48 hours
79
  17.3%
43
  18.6%
79
  21.0%
201
  18.9%
Influenza Virus Type or Subtype on RT-PCR Assay at Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 456 participants 231 participants 377 participants 1064 participants
A/H1N1pdm
7
   1.5%
7
   3.0%
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
   9.0%
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  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 456 participants 231 participants 377 participants 1064 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   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 456 participants 231 participants 377 participants 1064 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%
[1]
Measure 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.
1.Primary Outcome
Title Time to Alleviation of Symptoms in Participants Randomized to Baloxavir or Placebo
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 455 230
Median (95% Confidence Interval)
Unit of Measure: hours
53.7
(49.5 to 58.5)
80.2
(72.6 to 87.1)
Show Statistical Analysis 1 Hide 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 [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide 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 [Not Specified]
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).
2.Primary Outcome
Title Time to Alleviation of Symptoms in Adults Randomized to Baloxavir or Oseltamivir
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 375 377
Median (95% Confidence Interval)
Unit of Measure: hours
53.5
(48.0 to 58.5)
53.8
(50.2 to 56.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
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 [Not Specified]
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
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Analysis using the stratified log rank test was performed as a sensitivity analysis.
Type of Statistical Test Superiority
Comments [Not Specified]
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).
3.Secondary Outcome
Title Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 427 210
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Day 2 Number Analyzed 414 participants 201 participants
47.6
(42.7 to 52.5)
96.0
(92.3 to 98.3)
Day 3 Number Analyzed 406 participants 193 participants
21.7
(17.8 to 26.0)
70.5
(63.5 to 76.8)
Day 4 Number Analyzed 114 participants 57 participants
16.7
(10.3 to 24.8)
56.1
(42.4 to 69.3)
Day 5 Number Analyzed 406 participants 192 participants
13.5
(10.4 to 17.3)
29.7
(23.3 to 36.7)
Day 6 Number Analyzed 97 participants 48 participants
8.2
(3.6 to 15.6)
12.5
(4.7 to 25.2)
Day 9 Number Analyzed 408 participants 197 participants
2.9
(1.5 to 5.1)
4.6
(2.1 to 8.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 2
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 3
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 4
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 5
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 6
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 9
Type of Statistical Test Superiority
Comments [Not Specified]
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).
4.Secondary Outcome
Title Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 352 359
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Day 2 Number Analyzed 340 participants 348 participants
47.4
(41.9 to 52.8)
91.1
(87.6 to 93.9)
Day 3 Number Analyzed 335 participants 344 participants
20.0
(15.8 to 24.7)
57.3
(51.9 to 62.6)
Day 4 Number Analyzed 87 participants 105 participants
16.1
(9.1 to 25.5)
27.6
(19.3 to 37.2)
Day 5 Number Analyzed 333 participants 336 participants
12.9
(9.5 to 17.0)
20.8
(16.6 to 25.6)
Day 6 Number Analyzed 71 participants 78 participants
5.6
(1.6 to 13.8)
9.0
(3.7 to 17.6)
Day 9 Number Analyzed 336 participants 340 participants
3.0
(1.4 to 5.4)
3.2
(1.6 to 5.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 2
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 3
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 4
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 5
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 6
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 9
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 456 231
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Day 2 Number Analyzed 443 participants 222 participants
97.3
(95.3 to 98.6)
97.7
(94.8 to 99.3)
Day 3 Number Analyzed 436 participants 214 participants
95.6
(93.3 to 97.4)
97.2
(94.0 to 99.0)
Day 4 Number Analyzed 122 participants 67 participants
93.4
(87.5 to 97.1)
91.0
(81.5 to 96.6)
Day 5 Number Analyzed 436 participants 213 participants
87.4
(83.9 to 90.4)
93.9
(89.8 to 96.7)
Day 6 Number Analyzed 103 participants 57 participants
74.8
(65.2 to 82.8)
77.2
(64.2 to 87.3)
Day 9 Number Analyzed 436 participants 217 participants
61.5
(56.7 to 66.1)
72.4
(65.9 to 78.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 2
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 3
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 4
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 5
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 6
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 9
Type of Statistical Test Superiority
Comments [Not Specified]
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).
6.Secondary Outcome
Title Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 376 377
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Day 2 Number Analyzed 364 participants 362 participants
97.3
(95.0 to 98.7)
98.6
(96.8 to 99.6)
Day 3 Number Analyzed 360 participants 362 participants
95.3
(92.5 to 97.2)
97.5
(95.3 to 98.9)
Day 4 Number Analyzed 94 participants 115 participants
93.6
(86.6 to 97.6)
93.0
(86.8 to 96.9)
Day 5 Number Analyzed 358 participants 353 participants
86.6
(82.6 to 89.9)
92.1
(88.7 to 94.7)
Day 6 Number Analyzed 75 participants 83 participants
69.3
(57.6 to 79.5)
80.7
(70.6 to 88.6)
Day 9 Number Analyzed 359 participants 360 participants
60.2
(54.9 to 65.3)
64.7
(59.5 to 69.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 2
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 3
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 4
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 5
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 6
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 9
Type of Statistical Test Superiority
Comments [Not Specified]
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).
7.Secondary Outcome
Title Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 427 210
Mean (Standard Deviation)
Unit of Measure: log₁₀[TCID₅₀/mL]
Day 2 Number Analyzed 414 participants 201 participants
-4.45  (2.03) -1.19  (2.43)
Day 3 Number Analyzed 406 participants 193 participants
-4.82  (1.99) -2.88  (2.88)
Day 4 Number Analyzed 114 participants 57 participants
-4.50  (2.02) -3.31  (2.34)
Day 5 Number Analyzed 406 participants 192 participants
-4.95  (1.93) -4.47  (2.21)
Day 6 Number Analyzed 97 participants 48 participants
-4.58  (1.99) -4.68  (2.12)
Day 9 Number Analyzed 408 participants 197 participants
-5.06  (1.87) -4.87  (1.85)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 2
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 3
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 4
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 5
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 6
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 9
Type of Statistical Test Superiority
Comments [Not Specified]
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).
8.Secondary Outcome
Title Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 352 359
Mean (Standard Deviation)
Unit of Measure: log₁₀[TCID₅₀/mL]
Day 2 Number Analyzed 340 participants 348 participants
-4.39  (2.07) -2.53  (2.03)
Day 3 Number Analyzed 335 participants 344 participants
-4.79  (2.03) -4.20  (2.02)
Day 4 Number Analyzed 87 participants 105 participants
-4.46  (2.03) -4.63  (1.89)
Day 5 Number Analyzed 333 participants 336 participants
-4.95  (1.94) -4.98  (1.81)
Day 6 Number Analyzed 71 participants 78 participants
-4.56  (1.99) -4.85  (1.95)
Day 9 Number Analyzed 336 participants 340 participants
-5.03  (1.89) -5.22  (1.70)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 2
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 3
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 4
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 5
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 6
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 9
Type of Statistical Test Superiority
Comments [Not Specified]
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).
9.Secondary Outcome
Title Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 456 231
Mean (Standard Deviation)
Unit of Measure: log₁₀ virus particles/mL
Day 2 Number Analyzed 431 participants 213 participants
-1.63  (1.03) -0.56  (1.37)
Day 3 Number Analyzed 424 participants 205 participants
-2.80  (1.20) -1.61  (1.76)
Day 4 Number Analyzed 120 participants 66 participants
-3.07  (1.59) -1.95  (1.76)
Day 5 Number Analyzed 424 participants 204 participants
-3.75  (1.47) -3.04  (1.62)
Day 6 Number Analyzed 101 participants 56 participants
-3.83  (1.64) -3.03  (1.85)
Day 9 Number Analyzed 426 participants 208 participants
-4.43  (1.42) -4.06  (1.47)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 2
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 3
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 4
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 5
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 6
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments Day 9
Type of Statistical Test Superiority
Comments [Not Specified]
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).
10.Secondary Outcome
Title Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 376 377
Mean (Standard Deviation)
Unit of Measure: log₁₀ virus particles/mL
Day 2 Number Analyzed 355 participants 354 participants
-1.61  (1.06) -1.10  (1.10)
Day 3 Number Analyzed 350 participants 352 participants
-2.79  (1.21) -2.44  (1.24)
Day 4 Number Analyzed 92 participants 112 participants
-2.94  (1.62) -2.97  (1.29)
Day 5 Number Analyzed 348 participants 343 participants
-3.76  (1.44) -3.62  (1.34)
Day 6 Number Analyzed 73 participants 81 participants
-3.81  (1.52) -3.88  (1.35)
Day 9 Number Analyzed 351 participants 349 participants
-4.43  (1.43) -4.52  (1.22)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 2
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 3
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 4
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 5
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 6
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments Day 9
Type of Statistical Test Superiority
Comments [Not Specified]
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).
11.Secondary Outcome
Title Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Participants Randomized to Baloxavir or Placebo
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 408 197
Mean (Standard Deviation)
Unit of Measure: log₁₀[TCID₅₀/mL]*hours
-836.2  (348.9) -641.8  (377.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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).
12.Secondary Outcome
Title Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Adults Randomized to Baloxavir or Oseltamivir
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 336 340
Mean (Standard Deviation)
Unit of Measure: log₁₀[TCID₅₀/mL]*hours
-829.6  (350.3) -790.2  (328.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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).
13.Secondary Outcome
Title Area Under the Curve (AUC) Adjusted by Baseline of Influenza Virus RNA in Participants Randomized to Baloxavir or Placebo
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 426 208
Mean (Standard Deviation)
Unit of Measure: log₁₀ virus particles/mL*hours
-582.0  (230.9) -456.8  (269.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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).
14.Secondary Outcome
Title Area Under the Curve (AUC) Adjusted by Baseline of Influenza Virus RNA in Adults Randomized to Baloxavir or Oseltamivir
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 351 349
Mean (Standard Deviation)
Unit of Measure: log₁₀ virus particles/mL*hours
-581.0  (231.2) -569.7  (228.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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).
15.Secondary Outcome
Title Time to Cessation of Viral Shedding Determined by Virus Titer in Participants Randomized to Baloxavir or Placebo
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 426 209
Median (95% Confidence Interval)
Unit of Measure: hours
24.0
(24.0 to 48.0)
96.0 [1] 
(NA to NA)
[1]
Could not be estimated because lower limit of 95% CI of KM survival function just before the median survival time was higher than 50% and an upper limit of 95% CI of KM survival function just after the median survival time was lower than 50%.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Time to Cessation of Viral Shedding Determined by Virus Titer in Adults Randomized to Baloxavir or Oseltamivir
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 351 357
Median (95% Confidence Interval)
Unit of Measure: hours
24.0
(24.0 to 48.0)
72.0
(72.0 to 96.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Time to Cessation of Viral Shedding Determined by Virus RNA in Participants Randomized to Baloxavir or Placebo
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 455 230
Median (95% Confidence Interval)
Unit of Measure: hours
216.0
(216.0 to 240.0)
240.0
(240.0 to 336.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Time to Cessation of Viral Shedding Determined by Virus RNA in Adults Randomized to Baloxavir or Oseltamivir
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 375 375
Median (95% Confidence Interval)
Unit of Measure: hours
216.0
(192.0 to 240.0)
240.0
(216.0 to 240.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 456 231
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
12 hours Number Analyzed 373 participants 197 participants
9.7
(6.9 to 13.1)
8.1
(4.7 to 12.9)
24 hours Number Analyzed 445 participants 218 participants
23.1
(19.3 to 27.3)
12.8
(8.7 to 18.0)
36 hours Number Analyzed 361 participants 195 participants
42.4
(37.2 to 47.7)
23.1
(17.4 to 29.6)
48 hours Number Analyzed 444 participants 220 participants
50.7
(45.9 to 55.4)
26.4
(20.7 to 32.7)
72 hours Number Analyzed 431 participants 216 participants
68.9
(64.3 to 73.3)
49.5
(42.7 to 56.4)
96 hours Number Analyzed 429 participants 216 participants
78.6
(74.4 to 82.3)
69.9
(63.3 to 75.9)
120 hours Number Analyzed 415 participants 212 participants
85.5
(81.8 to 88.8)
81.6
(75.7 to 86.6)
144 hours Number Analyzed 404 participants 199 participants
89.1
(85.7 to 92.0)
85.4
(79.7 to 90.0)
168 hours Number Analyzed 403 participants 197 participants
91.6
(88.4 to 94.1)
88.3
(83.0 to 92.5)
192 hours Number Analyzed 406 participants 197 participants
90.9
(87.7 to 93.5)
91.4
(86.5 to 94.9)
216 hours Number Analyzed 224 participants 111 participants
91.1
(86.5 to 94.5)
91.9
(85.2 to 96.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 12 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 24 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 36 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 48 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 72 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 96 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 120 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 144 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 168 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 192 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 216 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
20.Secondary Outcome
Title Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 376 377
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
12 hours Number Analyzed 310 participants 309 participants
8.7
(5.8 to 12.4)
4.9
(2.7 to 7.9)
24 hours Number Analyzed 366 participants 365 participants
21.3
(17.2 to 25.9)
22.7
(18.5 to 27.4)
36 hours Number Analyzed 299 participants 297 participants
41.1
(35.5 to 46.9)
38.7
(33.1 to 44.5)
48 hours Number Analyzed 365 participants 360 participants
51.0
(45.7 to 56.2)
54.4
(49.1 to 59.7)
72 hours Number Analyzed 351 participants 359 participants
70.7
(65.6 to 75.4)
73.0
(68.1 to 77.5)
96 hours Number Analyzed 351 participants 359 participants
79.8
(75.2 to 83.9)
80.5
(76.0 to 84.5)
120 hours Number Analyzed 339 participants 345 participants
86.1
(82.0 to 89.6)
87.0
(82.9 to 90.3)
144 hours Number Analyzed 334 participants 334 participants
89.2
(85.4 to 92.3)
91.3
(87.8 to 94.1)
168 hours Number Analyzed 336 participants 334 participants
91.4
(87.8 to 94.1)
94.3
(91.3 to 96.5)
192 hours Number Analyzed 338 participants 331 participants
90.8
(87.2 to 93.7)
95.5
(92.6 to 97.4)
216 hours Number Analyzed 187 participants 188 participants
90.9
(85.8 to 94.6)
96.3
(92.5 to 98.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments 12 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments 24 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments 36 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments 48 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments 72 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments 96 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments 120 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments 144 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments 168 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments 192 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments 216 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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).
21.Secondary Outcome
Title Time to Alleviation of the Four Systemic Symptoms in Participants Randomized to Baloxavir or Placebo
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 455 230
Median (95% Confidence Interval)
Unit of Measure: hours
33.8
(31.0 to 38.3)
53.5
(45.9 to 57.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Time to Alleviation of the Four Systemic Symptoms in Adults Randomized to Baloxavir or Oseltamivir
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 375 377
Median (95% Confidence Interval)
Unit of Measure: hours
36.7
(32.0 to 40.1)
37.4
(31.5 to 42.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Time to Alleviation of the Three Respiratory Symptoms in Participants Randomized to Baloxavir or Placebo
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 455 230
Median (95% Confidence Interval)
Unit of Measure: hours
46.0
(43.4 to 50.6)
69.1
(63.9 to 78.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments [Not Specified]
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 [Not Specified]
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
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Time to Alleviation of the Three Respiratory Symptoms in Adults Randomized to Baloxavir or Oseltamivir
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 375 377
Median (95% Confidence Interval)
Unit of Measure: hours
46.0
(42.7 to 52.0)
44.6
(40.6 to 49.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
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
Estimation Comments [Not Specified]
25.Secondary Outcome
Title Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo
Hide 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 at each time point.

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.
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 456 231
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
12 hours Number Analyzed 373 participants 197 participants
-2.4  (0.2) -2.5  (0.3)
24 hours Number Analyzed 445 participants 218 participants
-4.7  (0.2) -3.6  (0.3)
36 hours Number Analyzed 361 participants 195 participants
-6.7  (0.2) -4.9  (0.3)
48 hours Number Analyzed 444 participants 220 participants
-7.8  (0.2) -6.0  (0.3)
72 hours Number Analyzed 431 participants 216 participants
-9.4  (0.2) -8.0  (0.2)
96 hours Number Analyzed 429 participants 216 participants
-10.5  (0.2) -9.5  (0.2)
120 hours Number Analyzed 415 participants 212 participants
-10.9  (0.2) -10.6  (0.2)
144 hours Number Analyzed 404 participants 199 participants
-11.6  (0.1) -11.2  (0.2)
168 hours Number Analyzed 403 participants 197 participants
-11.9  (0.1) -11.8  (0.2)
192 hours Number Analyzed 406 participants 197 participants
-12.0  (0.1) -12.0  (0.2)
216 hours Number Analyzed 224 participants 111 participants
-12.4  (0.2) -12.4  (0.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 12 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 24 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 36 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 48 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 72 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 96 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 120 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 144 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 168 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 192 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Baloxavir, Placebo
Comments 216 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
26.Secondary Outcome
Title Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Hide 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 at each time point.

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.
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 376 377
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
12 hours Number Analyzed 310 participants 309 participants
-2.2  (0.2) -2.4  (0.2)
24 hours Number Analyzed 366 participants 365 participants
-4.5  (0.2) -4.7  (0.2)
36 hours Number Analyzed 299 participants 297 participants
-6.5  (0.2) -6.3  (0.2)
48 hours Number Analyzed 365 participants 360 participants
-7.6  (0.2) -7.8  (0.2)
72 hours Number Analyzed 351 participants 359 participants
-9.6  (0.2) -9.7  (0.2)
96 hours Number Analyzed 351 participants 359 participants
-10.5  (0.2) -10.6  (0.2)
120 hours Number Analyzed 339 participants 345 participants
-11.0  (0.2) -11.3  (0.2)
144 hours Number Analyzed 334 participants 334 participants
-11.8  (0.2) -11.8  (0.2)
168 hours Number Analyzed 336 participants 334 participants
-11.9  (0.2) -12.1  (0.2)
192 hours Number Analyzed 338 participants 331 participants
-12.0  (0.1) -12.4  (0.2)
216 hours Number Analyzed 187 participants 188 participants
-12.4  (0.2) -12.5  (0.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments 12 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Baloxavir, Oseltamivir
Comments 24 hours
Type of Statistical Test Superiority
Comments [Not Specified]
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 [Not Specified]
Show Statistical Analysis 3