Trial Outcomes & Findings for A Study of S-033188 (Baloxavir Marboxil) Compared With Placebo or Oseltamivir in Otherwise Healthy Patients With Influenza (NCT NCT02954354)
NCT ID: NCT02954354
Last Updated: 2019-05-08
Results Overview
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.
COMPLETED
PHASE3
1436 participants
Initiation of study treatment up to Day 14
2019-05-08
Participant Flow
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.
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.
Participant milestones
| Measure |
Baloxavir
Participants aged 20 to 64 years received 40 mg or 80 mg baloxavir (depending on weight) orally on Day 1 and placebo to oseltamivir orally twice a day (BID) on Days 1 to 5.
Participants aged 12 to 19 years received 40 mg or 80 mg baloxavir (depending on weight) on Day 1.
|
Placebo
Participants aged 20 to 64 years received placebo to baloxavir on Day 1 and placebo to oseltamivir orally twice a day on Days 1 to 5. Participants aged 12 to 19 years received placebo to baloxavir on Day 1.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Overall Study
STARTED
|
612
|
310
|
514
|
|
Overall Study
Received Study Drug
|
610
|
309
|
513
|
|
Overall Study
Intention to Treat Infected Population
|
456
|
231
|
377
|
|
Overall Study
COMPLETED
|
578
|
290
|
498
|
|
Overall Study
NOT COMPLETED
|
34
|
20
|
16
|
Reasons for withdrawal
| Measure |
Baloxavir
Participants aged 20 to 64 years received 40 mg or 80 mg baloxavir (depending on weight) orally on Day 1 and placebo to oseltamivir orally twice a day (BID) on Days 1 to 5.
Participants aged 12 to 19 years received 40 mg or 80 mg baloxavir (depending on weight) on Day 1.
|
Placebo
Participants aged 20 to 64 years received placebo to baloxavir on Day 1 and placebo to oseltamivir orally twice a day on Days 1 to 5. Participants aged 12 to 19 years received placebo to baloxavir on Day 1.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
2
|
2
|
4
|
|
Overall Study
Failure to Meet Eligibility Criteria
|
1
|
0
|
0
|
|
Overall Study
Lack of Efficacy
|
0
|
2
|
0
|
|
Overall Study
Withdrawal by Subject
|
17
|
9
|
11
|
|
Overall Study
Lost to Follow-up
|
12
|
5
|
0
|
|
Overall Study
Miscellaneous
|
2
|
2
|
1
|
Baseline Characteristics
A Study of S-033188 (Baloxavir Marboxil) Compared With Placebo or Oseltamivir in Otherwise Healthy Patients With Influenza
Baseline characteristics by cohort
| Measure |
Baloxavir
n=456 Participants
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.
|
Placebo
n=231 Participants
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.
|
Oseltamivir
n=377 Participants
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
n=1064 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
33.5 Years
STANDARD_DEVIATION 13.5 • n=5 Participants
|
33.9 Years
STANDARD_DEVIATION 13.7 • n=7 Participants
|
36.0 Years
STANDARD_DEVIATION 11.8 • n=5 Participants
|
34.5 Years
STANDARD_DEVIATION 13.0 • n=4 Participants
|
|
Age, Customized
≥ 12 to ≤ 19 years
|
80 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
118 Participants
n=4 Participants
|
|
Age, Customized
≥ 20 to ≤ 29 years
|
121 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
134 Participants
n=5 Participants
|
316 Participants
n=4 Participants
|
|
Age, Customized
≥ 30 to ≤ 39 years
|
92 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
104 Participants
n=5 Participants
|
243 Participants
n=4 Participants
|
|
Age, Customized
≥ 40 to ≤ 49 years
|
97 Participants
n=5 Participants
|
48 Participants
n=7 Participants
|
77 Participants
n=5 Participants
|
222 Participants
n=4 Participants
|
|
Age, Customized
≥ 50 to ≤ 59 years
|
52 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
133 Participants
n=4 Participants
|
|
Age, Customized
≥ 60 to ≤ 64 years
|
14 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
32 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
224 Participants
n=5 Participants
|
111 Participants
n=7 Participants
|
159 Participants
n=5 Participants
|
494 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
232 Participants
n=5 Participants
|
120 Participants
n=7 Participants
|
218 Participants
n=5 Participants
|
570 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
32 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
68 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
424 Participants
n=5 Participants
|
220 Participants
n=7 Participants
|
352 Participants
n=5 Participants
|
996 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
349 Participants
n=5 Participants
|
178 Participants
n=7 Participants
|
305 Participants
n=5 Participants
|
832 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
18 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
38 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
85 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
185 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Other
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
|
Time From Symptom Onset to Initiation of the Trial Regimen
≥ 0 to ≤ 12 hours
|
60 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
135 Participants
n=4 Participants
|
|
Time From Symptom Onset to Initiation of the Trial Regimen
> 12 to ≤ 24 hours
|
178 Participants
n=5 Participants
|
87 Participants
n=7 Participants
|
163 Participants
n=5 Participants
|
428 Participants
n=4 Participants
|
|
Time From Symptom Onset to Initiation of the Trial Regimen
> 24 to ≤ 36 hours
|
139 Participants
n=5 Participants
|
67 Participants
n=7 Participants
|
94 Participants
n=5 Participants
|
300 Participants
n=4 Participants
|
|
Time From Symptom Onset to Initiation of the Trial Regimen
> 36 to ≤ 48 hours
|
79 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
79 Participants
n=5 Participants
|
201 Participants
n=4 Participants
|
|
Influenza Virus Type or Subtype on RT-PCR Assay at Enrollment
A/H1N1pdm
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
|
Influenza Virus Type or Subtype on RT-PCR Assay at Enrollment
A/H3
|
393 Participants
n=5 Participants
|
196 Participants
n=7 Participants
|
332 Participants
n=5 Participants
|
921 Participants
n=4 Participants
|
|
Influenza Virus Type or Subtype on RT-PCR Assay at Enrollment
B
|
38 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
92 Participants
n=4 Participants
|
|
Influenza Virus Type or Subtype on RT-PCR Assay at Enrollment
Mixed infection
|
8 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
|
Influenza Virus Type or Subtype on RT-PCR Assay at Enrollment
Other
|
10 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
|
Region
Japan/Asia
|
343 Participants
n=5 Participants
|
175 Participants
n=7 Participants
|
303 Participants
n=5 Participants
|
821 Participants
n=4 Participants
|
|
Region
Rest of the world
|
113 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
74 Participants
n=5 Participants
|
243 Participants
n=4 Participants
|
|
Composite Symptom Score
≤ 11
|
144 Participants
n=5 Participants
|
72 Participants
n=7 Participants
|
119 Participants
n=5 Participants
|
335 Participants
n=4 Participants
|
|
Composite Symptom Score
≥ 12
|
312 Participants
n=5 Participants
|
159 Participants
n=7 Participants
|
258 Participants
n=5 Participants
|
729 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Initiation of study treatment up to Day 14Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo with available time to alleviation of symptoms data.
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.
Outcome measures
| Measure |
Baloxavir
n=455 Participants
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.
|
Placebo
n=230 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Time to Alleviation of Symptoms in Participants Randomized to Baloxavir or Placebo
|
53.7 hours
Interval 49.5 to 58.5
|
80.2 hours
Interval 72.6 to 87.1
|
—
|
PRIMARY outcome
Timeframe: Initiation of study treatment up to Day 14Population: 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.
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.
Outcome measures
| Measure |
Baloxavir
n=375 Participants
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.
|
Placebo
n=377 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Time to Alleviation of Symptoms in Adults Randomized to Baloxavir or Oseltamivir
|
53.5 hours
Interval 48.0 to 58.5
|
53.8 hours
Interval 50.2 to 56.4
|
—
|
SECONDARY outcome
Timeframe: Days 2, 3, 4 (optional), 5, 6 (optional), and 9Population: 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.
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.
Outcome measures
| Measure |
Baloxavir
n=427 Participants
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.
|
Placebo
n=210 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 2
|
47.6 percentage of participants
Interval 42.7 to 52.5
|
96.0 percentage of participants
Interval 92.3 to 98.3
|
—
|
|
Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 3
|
21.7 percentage of participants
Interval 17.8 to 26.0
|
70.5 percentage of participants
Interval 63.5 to 76.8
|
—
|
|
Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 4
|
16.7 percentage of participants
Interval 10.3 to 24.8
|
56.1 percentage of participants
Interval 42.4 to 69.3
|
—
|
|
Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 5
|
13.5 percentage of participants
Interval 10.4 to 17.3
|
29.7 percentage of participants
Interval 23.3 to 36.7
|
—
|
|
Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 6
|
8.2 percentage of participants
Interval 3.6 to 15.6
|
12.5 percentage of participants
Interval 4.7 to 25.2
|
—
|
|
Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 9
|
2.9 percentage of participants
Interval 1.5 to 5.1
|
4.6 percentage of participants
Interval 2.1 to 8.5
|
—
|
SECONDARY outcome
Timeframe: Days 2, 3, 4 (optional), 5, 6 (optional), and 9Population: 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.
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.
Outcome measures
| Measure |
Baloxavir
n=352 Participants
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.
|
Placebo
n=359 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 2
|
47.4 percentage of participants
Interval 41.9 to 52.8
|
91.1 percentage of participants
Interval 87.6 to 93.9
|
—
|
|
Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 3
|
20.0 percentage of participants
Interval 15.8 to 24.7
|
57.3 percentage of participants
Interval 51.9 to 62.6
|
—
|
|
Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 4
|
16.1 percentage of participants
Interval 9.1 to 25.5
|
27.6 percentage of participants
Interval 19.3 to 37.2
|
—
|
|
Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 5
|
12.9 percentage of participants
Interval 9.5 to 17.0
|
20.8 percentage of participants
Interval 16.6 to 25.6
|
—
|
|
Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 6
|
5.6 percentage of participants
Interval 1.6 to 13.8
|
9.0 percentage of participants
Interval 3.7 to 17.6
|
—
|
|
Percentage of Participants With Positive Influenza Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 9
|
3.0 percentage of participants
Interval 1.4 to 5.4
|
3.2 percentage of participants
Interval 1.6 to 5.7
|
—
|
SECONDARY outcome
Timeframe: Days 2, 3, 4 (optional), 5, 6 (optional), and 9Population: 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.
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.
Outcome measures
| Measure |
Baloxavir
n=456 Participants
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.
|
Placebo
n=231 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 2
|
97.3 percentage of participants
Interval 95.3 to 98.6
|
97.7 percentage of participants
Interval 94.8 to 99.3
|
—
|
|
Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 3
|
95.6 percentage of participants
Interval 93.3 to 97.4
|
97.2 percentage of participants
Interval 94.0 to 99.0
|
—
|
|
Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 4
|
93.4 percentage of participants
Interval 87.5 to 97.1
|
91.0 percentage of participants
Interval 81.5 to 96.6
|
—
|
|
Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 5
|
87.4 percentage of participants
Interval 83.9 to 90.4
|
93.9 percentage of participants
Interval 89.8 to 96.7
|
—
|
|
Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 6
|
74.8 percentage of participants
Interval 65.2 to 82.8
|
77.2 percentage of participants
Interval 64.2 to 87.3
|
—
|
|
Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 9
|
61.5 percentage of participants
Interval 56.7 to 66.1
|
72.4 percentage of participants
Interval 65.9 to 78.2
|
—
|
SECONDARY outcome
Timeframe: Days 2, 3, 4 (optional), 5, 6 (optional), and 9Population: 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.
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.
Outcome measures
| Measure |
Baloxavir
n=376 Participants
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.
|
Placebo
n=377 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 4
|
93.6 percentage of participants
Interval 86.6 to 97.6
|
93.0 percentage of participants
Interval 86.8 to 96.9
|
—
|
|
Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 5
|
86.6 percentage of participants
Interval 82.6 to 89.9
|
92.1 percentage of participants
Interval 88.7 to 94.7
|
—
|
|
Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 2
|
97.3 percentage of participants
Interval 95.0 to 98.7
|
98.6 percentage of participants
Interval 96.8 to 99.6
|
—
|
|
Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 3
|
95.3 percentage of participants
Interval 92.5 to 97.2
|
97.5 percentage of participants
Interval 95.3 to 98.9
|
—
|
|
Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 6
|
69.3 percentage of participants
Interval 57.6 to 79.5
|
80.7 percentage of participants
Interval 70.6 to 88.6
|
—
|
|
Percentage of Participants With Positive Influenza Virus by RT-PCR at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 9
|
60.2 percentage of participants
Interval 54.9 to 65.3
|
64.7 percentage of participants
Interval 59.5 to 69.7
|
—
|
SECONDARY outcome
Timeframe: Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9Population: 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.
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).
Outcome measures
| Measure |
Baloxavir
n=427 Participants
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.
|
Placebo
n=210 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 2
|
-4.45 log₁₀[TCID₅₀/mL]
Standard Deviation 2.03
|
-1.19 log₁₀[TCID₅₀/mL]
Standard Deviation 2.43
|
—
|
|
Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 3
|
-4.82 log₁₀[TCID₅₀/mL]
Standard Deviation 1.99
|
-2.88 log₁₀[TCID₅₀/mL]
Standard Deviation 2.88
|
—
|
|
Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 4
|
-4.50 log₁₀[TCID₅₀/mL]
Standard Deviation 2.02
|
-3.31 log₁₀[TCID₅₀/mL]
Standard Deviation 2.34
|
—
|
|
Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 5
|
-4.95 log₁₀[TCID₅₀/mL]
Standard Deviation 1.93
|
-4.47 log₁₀[TCID₅₀/mL]
Standard Deviation 2.21
|
—
|
|
Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 6
|
-4.58 log₁₀[TCID₅₀/mL]
Standard Deviation 1.99
|
-4.68 log₁₀[TCID₅₀/mL]
Standard Deviation 2.12
|
—
|
|
Change From Baseline in Virus Titer at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 9
|
-5.06 log₁₀[TCID₅₀/mL]
Standard Deviation 1.87
|
-4.87 log₁₀[TCID₅₀/mL]
Standard Deviation 1.85
|
—
|
SECONDARY outcome
Timeframe: Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9Population: 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.
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).
Outcome measures
| Measure |
Baloxavir
n=352 Participants
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.
|
Placebo
n=359 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 2
|
-4.39 log₁₀[TCID₅₀/mL]
Standard Deviation 2.07
|
-2.53 log₁₀[TCID₅₀/mL]
Standard Deviation 2.03
|
—
|
|
Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 3
|
-4.79 log₁₀[TCID₅₀/mL]
Standard Deviation 2.03
|
-4.20 log₁₀[TCID₅₀/mL]
Standard Deviation 2.02
|
—
|
|
Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 4
|
-4.46 log₁₀[TCID₅₀/mL]
Standard Deviation 2.03
|
-4.63 log₁₀[TCID₅₀/mL]
Standard Deviation 1.89
|
—
|
|
Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 5
|
-4.95 log₁₀[TCID₅₀/mL]
Standard Deviation 1.94
|
-4.98 log₁₀[TCID₅₀/mL]
Standard Deviation 1.81
|
—
|
|
Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 6
|
-4.56 log₁₀[TCID₅₀/mL]
Standard Deviation 1.99
|
-4.85 log₁₀[TCID₅₀/mL]
Standard Deviation 1.95
|
—
|
|
Change From Baseline in Virus Titer at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 9
|
-5.03 log₁₀[TCID₅₀/mL]
Standard Deviation 1.89
|
-5.22 log₁₀[TCID₅₀/mL]
Standard Deviation 1.70
|
—
|
SECONDARY outcome
Timeframe: Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9Population: 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.
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).
Outcome measures
| Measure |
Baloxavir
n=456 Participants
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.
|
Placebo
n=231 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 2
|
-1.63 log₁₀ virus particles/mL
Standard Deviation 1.03
|
-0.56 log₁₀ virus particles/mL
Standard Deviation 1.37
|
—
|
|
Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 3
|
-2.80 log₁₀ virus particles/mL
Standard Deviation 1.20
|
-1.61 log₁₀ virus particles/mL
Standard Deviation 1.76
|
—
|
|
Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 4
|
-3.07 log₁₀ virus particles/mL
Standard Deviation 1.59
|
-1.95 log₁₀ virus particles/mL
Standard Deviation 1.76
|
—
|
|
Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 5
|
-3.75 log₁₀ virus particles/mL
Standard Deviation 1.47
|
-3.04 log₁₀ virus particles/mL
Standard Deviation 1.62
|
—
|
|
Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 6
|
-3.83 log₁₀ virus particles/mL
Standard Deviation 1.64
|
-3.03 log₁₀ virus particles/mL
Standard Deviation 1.85
|
—
|
|
Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Participants Randomized to Baloxavir or Placebo
Day 9
|
-4.43 log₁₀ virus particles/mL
Standard Deviation 1.42
|
-4.06 log₁₀ virus particles/mL
Standard Deviation 1.47
|
—
|
SECONDARY outcome
Timeframe: Day 1 pretreatment (Baseline) and Days 2, 3, 4 (optional), 5, 6 (optional), and 9Population: 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.
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).
Outcome measures
| Measure |
Baloxavir
n=376 Participants
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.
|
Placebo
n=377 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 2
|
-1.61 log₁₀ virus particles/mL
Standard Deviation 1.06
|
-1.10 log₁₀ virus particles/mL
Standard Deviation 1.10
|
—
|
|
Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 3
|
-2.79 log₁₀ virus particles/mL
Standard Deviation 1.21
|
-2.44 log₁₀ virus particles/mL
Standard Deviation 1.24
|
—
|
|
Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 4
|
-2.94 log₁₀ virus particles/mL
Standard Deviation 1.62
|
-2.97 log₁₀ virus particles/mL
Standard Deviation 1.29
|
—
|
|
Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 5
|
-3.76 log₁₀ virus particles/mL
Standard Deviation 1.44
|
-3.62 log₁₀ virus particles/mL
Standard Deviation 1.34
|
—
|
|
Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 6
|
-3.81 log₁₀ virus particles/mL
Standard Deviation 1.52
|
-3.88 log₁₀ virus particles/mL
Standard Deviation 1.35
|
—
|
|
Change From Baseline in Virus RNA (RT-PCR) at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
Day 9
|
-4.43 log₁₀ virus particles/mL
Standard Deviation 1.43
|
-4.52 log₁₀ virus particles/mL
Standard Deviation 1.22
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Day 9Population: 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.
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.
Outcome measures
| Measure |
Baloxavir
n=408 Participants
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.
|
Placebo
n=197 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Participants Randomized to Baloxavir or Placebo
|
-836.2 log₁₀[TCID₅₀/mL]*hours
Standard Deviation 348.9
|
-641.8 log₁₀[TCID₅₀/mL]*hours
Standard Deviation 377.6
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Day 9Population: 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.
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.
Outcome measures
| Measure |
Baloxavir
n=336 Participants
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.
|
Placebo
n=340 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Area Under the Curve (AUC) Adjusted by Baseline in Influenza Virus Titer in Adults Randomized to Baloxavir or Oseltamivir
|
-829.6 log₁₀[TCID₅₀/mL]*hours
Standard Deviation 350.3
|
-790.2 log₁₀[TCID₅₀/mL]*hours
Standard Deviation 328.4
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Day 9Population: 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.
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.
Outcome measures
| Measure |
Baloxavir
n=426 Participants
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.
|
Placebo
n=208 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Area Under the Curve (AUC) Adjusted by Baseline of Influenza Virus RNA in Participants Randomized to Baloxavir or Placebo
|
-582.0 log₁₀ virus particles/mL*hours
Standard Deviation 230.9
|
-456.8 log₁₀ virus particles/mL*hours
Standard Deviation 269.6
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Day 9Population: 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.
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.
Outcome measures
| Measure |
Baloxavir
n=351 Participants
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.
|
Placebo
n=349 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Area Under the Curve (AUC) Adjusted by Baseline of Influenza Virus RNA in Adults Randomized to Baloxavir or Oseltamivir
|
-581.0 log₁₀ virus particles/mL*hours
Standard Deviation 231.2
|
-569.7 log₁₀ virus particles/mL*hours
Standard Deviation 228.8
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Day 9Population: 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.
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.
Outcome measures
| Measure |
Baloxavir
n=426 Participants
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.
|
Placebo
n=209 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Time to Cessation of Viral Shedding Determined by Virus Titer in Participants Randomized to Baloxavir or Placebo
|
24.0 hours
Interval 24.0 to 48.0
|
96.0 hours
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%.
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Day 9Population: 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..
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.
Outcome measures
| Measure |
Baloxavir
n=351 Participants
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.
|
Placebo
n=357 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Time to Cessation of Viral Shedding Determined by Virus Titer in Adults Randomized to Baloxavir or Oseltamivir
|
24.0 hours
Interval 24.0 to 48.0
|
72.0 hours
Interval 72.0 to 96.0
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Day 9Population: 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.
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.
Outcome measures
| Measure |
Baloxavir
n=455 Participants
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.
|
Placebo
n=230 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Time to Cessation of Viral Shedding Determined by Virus RNA in Participants Randomized to Baloxavir or Placebo
|
216.0 hours
Interval 216.0 to 240.0
|
240.0 hours
Interval 240.0 to 336.0
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Day 9Population: 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.
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.
Outcome measures
| Measure |
Baloxavir
n=375 Participants
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.
|
Placebo
n=375 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Time to Cessation of Viral Shedding Determined by Virus RNA in Adults Randomized to Baloxavir or Oseltamivir
|
216.0 hours
Interval 192.0 to 240.0
|
240.0 hours
Interval 216.0 to 240.0
|
—
|
SECONDARY outcome
Timeframe: 12, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours after the initial dose of study treatmentPopulation: Participants in the intention-to-treat infection population assigned to baloxavir or placebo with available alleviation of symptoms data at each time point.
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) .
Outcome measures
| Measure |
Baloxavir
n=456 Participants
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.
|
Placebo
n=231 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo
12 hours
|
9.7 percentage of participants
Interval 6.9 to 13.1
|
8.1 percentage of participants
Interval 4.7 to 12.9
|
—
|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo
24 hours
|
23.1 percentage of participants
Interval 19.3 to 27.3
|
12.8 percentage of participants
Interval 8.7 to 18.0
|
—
|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo
36 hours
|
42.4 percentage of participants
Interval 37.2 to 47.7
|
23.1 percentage of participants
Interval 17.4 to 29.6
|
—
|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo
48 hours
|
50.7 percentage of participants
Interval 45.9 to 55.4
|
26.4 percentage of participants
Interval 20.7 to 32.7
|
—
|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo
72 hours
|
68.9 percentage of participants
Interval 64.3 to 73.3
|
49.5 percentage of participants
Interval 42.7 to 56.4
|
—
|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo
96 hours
|
78.6 percentage of participants
Interval 74.4 to 82.3
|
69.9 percentage of participants
Interval 63.3 to 75.9
|
—
|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo
120 hours
|
85.5 percentage of participants
Interval 81.8 to 88.8
|
81.6 percentage of participants
Interval 75.7 to 86.6
|
—
|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo
144 hours
|
89.1 percentage of participants
Interval 85.7 to 92.0
|
85.4 percentage of participants
Interval 79.7 to 90.0
|
—
|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo
168 hours
|
91.6 percentage of participants
Interval 88.4 to 94.1
|
88.3 percentage of participants
Interval 83.0 to 92.5
|
—
|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo
192 hours
|
90.9 percentage of participants
Interval 87.7 to 93.5
|
91.4 percentage of participants
Interval 86.5 to 94.9
|
—
|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Participants Randomized to Baloxavir or Placebo
216 hours
|
91.1 percentage of participants
Interval 86.5 to 94.5
|
91.9 percentage of participants
Interval 85.2 to 96.2
|
—
|
SECONDARY outcome
Timeframe: 12, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours after the initial dose of study treatmentPopulation: 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.
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) .
Outcome measures
| Measure |
Baloxavir
n=376 Participants
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.
|
Placebo
n=377 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
12 hours
|
8.7 percentage of participants
Interval 5.8 to 12.4
|
4.9 percentage of participants
Interval 2.7 to 7.9
|
—
|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
24 hours
|
21.3 percentage of participants
Interval 17.2 to 25.9
|
22.7 percentage of participants
Interval 18.5 to 27.4
|
—
|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
36 hours
|
41.1 percentage of participants
Interval 35.5 to 46.9
|
38.7 percentage of participants
Interval 33.1 to 44.5
|
—
|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
48 hours
|
51.0 percentage of participants
Interval 45.7 to 56.2
|
54.4 percentage of participants
Interval 49.1 to 59.7
|
—
|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
72 hours
|
70.7 percentage of participants
Interval 65.6 to 75.4
|
73.0 percentage of participants
Interval 68.1 to 77.5
|
—
|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
96 hours
|
79.8 percentage of participants
Interval 75.2 to 83.9
|
80.5 percentage of participants
Interval 76.0 to 84.5
|
—
|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
120 hours
|
86.1 percentage of participants
Interval 82.0 to 89.6
|
87.0 percentage of participants
Interval 82.9 to 90.3
|
—
|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
144 hours
|
89.2 percentage of participants
Interval 85.4 to 92.3
|
91.3 percentage of participants
Interval 87.8 to 94.1
|
—
|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
168 hours
|
91.4 percentage of participants
Interval 87.8 to 94.1
|
94.3 percentage of participants
Interval 91.3 to 96.5
|
—
|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
192 hours
|
90.8 percentage of participants
Interval 87.2 to 93.7
|
95.5 percentage of participants
Interval 92.6 to 97.4
|
—
|
|
Percentage of Participants Whose Symptoms Were Alleviated at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
216 hours
|
90.9 percentage of participants
Interval 85.8 to 94.6
|
96.3 percentage of participants
Interval 92.5 to 98.5
|
—
|
SECONDARY outcome
Timeframe: Initiation of study treatment up to Day 14Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo with available time to alleviation of the 4 systemic symptoms data.
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.
Outcome measures
| Measure |
Baloxavir
n=455 Participants
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.
|
Placebo
n=230 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Time to Alleviation of the Four Systemic Symptoms in Participants Randomized to Baloxavir or Placebo
|
33.8 hours
Interval 31.0 to 38.3
|
53.5 hours
Interval 45.9 to 57.3
|
—
|
SECONDARY outcome
Timeframe: Initiation of study treatment up to Day 14Population: 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.
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.
Outcome measures
| Measure |
Baloxavir
n=375 Participants
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.
|
Placebo
n=377 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Time to Alleviation of the Four Systemic Symptoms in Adults Randomized to Baloxavir or Oseltamivir
|
36.7 hours
Interval 32.0 to 40.1
|
37.4 hours
Interval 31.5 to 42.4
|
—
|
SECONDARY outcome
Timeframe: Initiation of study treatment up to Day 14Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo with available time to alleviation of the 3 respiratory symptoms data.
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.
Outcome measures
| Measure |
Baloxavir
n=455 Participants
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.
|
Placebo
n=230 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Time to Alleviation of the Three Respiratory Symptoms in Participants Randomized to Baloxavir or Placebo
|
46.0 hours
Interval 43.4 to 50.6
|
69.1 hours
Interval 63.9 to 78.1
|
—
|
SECONDARY outcome
Timeframe: Initiation of study treatment up to Day 14Population: 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.
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.
Outcome measures
| Measure |
Baloxavir
n=375 Participants
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.
|
Placebo
n=377 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Time to Alleviation of the Three Respiratory Symptoms in Adults Randomized to Baloxavir or Oseltamivir
|
46.0 hours
Interval 42.7 to 52.0
|
44.6 hours
Interval 40.6 to 49.5
|
—
|
SECONDARY outcome
Timeframe: Day 1 pretreatment (Baseline) and 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, and 216 hours after the initial dose of study treatment.Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo with available composite symptom scores at Baseline and each time point.
Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). The composite symptom score is the total score of the 7 influenza symptoms as assessed by the participant, and ranges from 0 to 21.
Outcome measures
| Measure |
Baloxavir
n=456 Participants
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.
|
Placebo
n=231 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo
12 hours
|
-2.4 scores on a scale
Standard Error 0.2
|
-2.5 scores on a scale
Standard Error 0.3
|
—
|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo
24 hours
|
-4.7 scores on a scale
Standard Error 0.2
|
-3.6 scores on a scale
Standard Error 0.3
|
—
|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo
36 hours
|
-6.7 scores on a scale
Standard Error 0.2
|
-4.9 scores on a scale
Standard Error 0.3
|
—
|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo
48 hours
|
-7.8 scores on a scale
Standard Error 0.2
|
-6.0 scores on a scale
Standard Error 0.3
|
—
|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo
72 hours
|
-9.4 scores on a scale
Standard Error 0.2
|
-8.0 scores on a scale
Standard Error 0.2
|
—
|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo
96 hours
|
-10.5 scores on a scale
Standard Error 0.2
|
-9.5 scores on a scale
Standard Error 0.2
|
—
|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo
120 hours
|
-10.9 scores on a scale
Standard Error 0.2
|
-10.6 scores on a scale
Standard Error 0.2
|
—
|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo
144 hours
|
-11.6 scores on a scale
Standard Error 0.1
|
-11.2 scores on a scale
Standard Error 0.2
|
—
|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo
168 hours
|
-11.9 scores on a scale
Standard Error 0.1
|
-11.8 scores on a scale
Standard Error 0.2
|
—
|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo
192 hours
|
-12.0 scores on a scale
Standard Error 0.1
|
-12.0 scores on a scale
Standard Error 0.2
|
—
|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Participants Randomized to Baloxavir or Placebo
216 hours
|
-12.4 scores on a scale
Standard Error 0.2
|
-12.4 scores on a scale
Standard Error 0.3
|
—
|
SECONDARY outcome
Timeframe: Day 1 pretreatment (Baseline) and 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, and 216 hours after the initial dose of study treatment.Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, with available composite symptom scores at Baseline and each time point.
Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). The composite symptom score is the total score of the 7 influenza symptoms as assessed by the participant, and ranges from 0 to 21.
Outcome measures
| Measure |
Baloxavir
n=376 Participants
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.
|
Placebo
n=377 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
12 hours
|
-2.2 scores on a scale
Standard Error 0.2
|
-2.4 scores on a scale
Standard Error 0.2
|
—
|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
24 hours
|
-4.5 scores on a scale
Standard Error 0.2
|
-4.7 scores on a scale
Standard Error 0.2
|
—
|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
36 hours
|
-6.5 scores on a scale
Standard Error 0.2
|
-6.3 scores on a scale
Standard Error 0.2
|
—
|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
48 hours
|
-7.6 scores on a scale
Standard Error 0.2
|
-7.8 scores on a scale
Standard Error 0.2
|
—
|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
72 hours
|
-9.6 scores on a scale
Standard Error 0.2
|
-9.7 scores on a scale
Standard Error 0.2
|
—
|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
96 hours
|
-10.5 scores on a scale
Standard Error 0.2
|
-10.6 scores on a scale
Standard Error 0.2
|
—
|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
120 hours
|
-11.0 scores on a scale
Standard Error 0.2
|
-11.3 scores on a scale
Standard Error 0.2
|
—
|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
144 hours
|
-11.8 scores on a scale
Standard Error 0.2
|
-11.8 scores on a scale
Standard Error 0.2
|
—
|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
168 hours
|
-11.9 scores on a scale
Standard Error 0.2
|
-12.1 scores on a scale
Standard Error 0.2
|
—
|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
192 hours
|
-12.0 scores on a scale
Standard Error 0.1
|
-12.4 scores on a scale
Standard Error 0.2
|
—
|
|
Change From Baseline in Composite Symptom Score at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
216 hours
|
-12.4 scores on a scale
Standard Error 0.2
|
-12.5 scores on a scale
Standard Error 0.2
|
—
|
SECONDARY outcome
Timeframe: Initiation of study treatment up to Day 14Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo whose body temperature at baseline was more than 37°C and time to resolution of fever was not missing.
Time to resolution of fever was defined as the time between the initiation of the study treatment and the resolution of fever. The resolution of fever was defined as the time when the participant's self-measured axillary temperature became less than 37ºC and was maintained at less than 37ºC for a duration of at least 12 hours. Time to resolution of fever was analyzed using KM methods; participants who did not experience resolution of fever by the last observation time point were censored at that time point.
Outcome measures
| Measure |
Baloxavir
n=448 Participants
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.
|
Placebo
n=230 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Time to Resolution of Fever in Participants Randomized to Baloxavir or Placebo
|
24.5 hours
Interval 22.6 to 26.6
|
42.0 hours
Interval 37.4 to 44.6
|
—
|
SECONDARY outcome
Timeframe: Initiation of study treatment up to Day 14Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, whose body temperature at baseline was more than 37°C and time to resolution of fever was not missing.
Time to resolution of fever was defined as the time between the initiation of the study treatment and the resolution of fever. The resolution of fever was defined as the time when the participant's self-measured axillary temperature became less than 37ºC and was maintained at less than 37ºC for a duration of at least 12 hours. Time to resolution of fever was analyzed using KM methods; participants who did not experience resolution of fever by the last observation time point were censored at that time point.
Outcome measures
| Measure |
Baloxavir
n=369 Participants
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.
|
Placebo
n=374 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Time to Resolution of Fever in Adults Randomized to Baloxavir or Oseltamivir
|
24.4 hours
Interval 22.2 to 26.5
|
24.0 hours
Interval 22.1 to 25.9
|
—
|
SECONDARY outcome
Timeframe: 12, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours after the initial dose of study treatmentPopulation: Participants in the intention-to-treat infection population assigned to baloxavir or placebo whose body temperature at baseline was more than 37°C with available body temperature data at each time point.
Defined as the percentage of patients whose axillary temperature dropped to less than 37ºC after the initiation of study treatment.
Outcome measures
| Measure |
Baloxavir
n=449 Participants
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.
|
Placebo
n=230 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
12 hours
|
26.5 percentage of participants
Interval 22.3 to 30.9
|
25.3 percentage of participants
Interval 19.7 to 31.7
|
—
|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
24 hours
|
64.3 percentage of participants
Interval 59.6 to 68.7
|
48.4 percentage of participants
Interval 41.8 to 55.2
|
—
|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
36 hours
|
80.8 percentage of participants
Interval 76.8 to 84.5
|
58.3 percentage of participants
Interval 51.4 to 64.9
|
—
|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
48 hours
|
89.3 percentage of participants
Interval 86.0 to 92.0
|
67.3 percentage of participants
Interval 60.6 to 73.4
|
—
|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
72 hours
|
93.7 percentage of participants
Interval 90.9 to 95.8
|
83.8 percentage of participants
Interval 77.8 to 88.6
|
—
|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
96 hours
|
92.8 percentage of participants
Interval 89.8 to 95.1
|
93.9 percentage of participants
Interval 89.6 to 96.8
|
—
|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
120 hours
|
92.9 percentage of participants
Interval 89.8 to 95.2
|
92.8 percentage of participants
Interval 88.2 to 96.0
|
—
|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
144 hours
|
93.4 percentage of participants
Interval 90.4 to 95.7
|
93.6 percentage of participants
Interval 89.1 to 96.6
|
—
|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
168 hours
|
93.3 percentage of participants
Interval 90.3 to 95.6
|
93.6 percentage of participants
Interval 89.1 to 96.6
|
—
|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
192 hours
|
94.1 percentage of participants
Interval 91.2 to 96.3
|
93.7 percentage of participants
Interval 89.3 to 96.7
|
—
|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
216 hours
|
92.5 percentage of participants
Interval 89.3 to 94.9
|
92.7 percentage of participants
Interval 88.0 to 95.9
|
—
|
SECONDARY outcome
Timeframe: 12, 24, 36, 48, 72, 96, 120, 144, 168, 192 and 216 hours after the initial dose of study treatmentPopulation: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, whose body temperature at baseline was more than 37°C with available body temperature data at each time point.
Defined as the percentage of patients whose axillary temperature dropped to less than 37ºC after the initiation of study treatment.
Outcome measures
| Measure |
Baloxavir
n=370 Participants
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.
|
Placebo
n=374 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
12 hours
|
25.0 percentage of participants
Interval 20.6 to 29.8
|
28.3 percentage of participants
Interval 23.7 to 33.3
|
—
|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
24 hours
|
64.3 percentage of participants
Interval 59.1 to 69.2
|
66.8 percentage of participants
Interval 61.7 to 71.6
|
—
|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
36 hours
|
81.9 percentage of participants
Interval 77.5 to 85.8
|
79.1 percentage of participants
Interval 74.5 to 83.2
|
—
|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
48 hours
|
90.1 percentage of participants
Interval 86.5 to 93.0
|
89.9 percentage of participants
Interval 86.3 to 92.8
|
—
|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
72 hours
|
93.8 percentage of participants
Interval 90.7 to 96.1
|
89.5 percentage of participants
Interval 85.8 to 92.6
|
—
|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
96 hours
|
93.9 percentage of participants
Interval 90.8 to 96.2
|
94.9 percentage of participants
Interval 92.0 to 97.0
|
—
|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
120 hours
|
93.8 percentage of participants
Interval 90.6 to 96.2
|
95.8 percentage of participants
Interval 93.1 to 97.7
|
—
|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
144 hours
|
92.8 percentage of participants
Interval 89.4 to 95.4
|
94.5 percentage of participants
Interval 91.5 to 96.7
|
—
|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
168 hours
|
93.6 percentage of participants
Interval 90.3 to 96.1
|
95.9 percentage of participants
Interval 93.0 to 97.8
|
—
|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
192 hours
|
94.6 percentage of participants
Interval 91.4 to 96.8
|
95.8 percentage of participants
Interval 92.9 to 97.7
|
—
|
|
Percentage of Participants Reporting Normal Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
216 hours
|
92.8 percentage of participants
Interval 89.3 to 95.4
|
94.5 percentage of participants
Interval 91.3 to 96.8
|
—
|
SECONDARY outcome
Timeframe: 12, 24, 36, 48, 72, 96 and 120 hours after the initial dose of study treatmentPopulation: Participants in the intention-to-treat infection population assigned to baloxavir or placebo with available temperature data at each time point.
Participant's self-measured axillary temperature using an electronic thermometer.
Outcome measures
| Measure |
Baloxavir
n=456 Participants
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.
|
Placebo
n=231 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
12 hours
|
37.40 °C
Standard Error 0.05
|
37.49 °C
Standard Error 0.07
|
—
|
|
Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
24 hours
|
36.73 °C
Standard Error 0.04
|
37.07 °C
Standard Error 0.05
|
—
|
|
Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
36 hours
|
36.49 °C
Standard Error 0.04
|
36.90 °C
Standard Error 0.05
|
—
|
|
Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
48 hours
|
36.32 °C
Standard Error 0.03
|
36.69 °C
Standard Error 0.05
|
—
|
|
Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
72 hours
|
36.26 °C
Standard Error 0.03
|
36.48 °C
Standard Error 0.04
|
—
|
|
Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
96 hours
|
36.27 °C
Standard Error 0.03
|
36.31 °C
Standard Error 0.04
|
—
|
|
Body Temperature at Each Time Point in Participants Randomized to Baloxavir or Placebo
120 hours
|
36.28 °C
Standard Error 0.03
|
36.25 °C
Standard Error 0.04
|
—
|
SECONDARY outcome
Timeframe: 12, 24, 36, 48, 72, 96 and 120 hours after the initial dose of study treatmentPopulation: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, with available temperature data at each time point.
Participant's self-measured axillary temperature using an electronic thermometer.
Outcome measures
| Measure |
Baloxavir
n=376 Participants
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.
|
Placebo
n=377 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
120 hours
|
36.27 °C
Standard Error 0.03
|
36.21 °C
Standard Error 0.03
|
—
|
|
Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
12 hours
|
37.47 °C
Standard Error 0.05
|
37.35 °C
Standard Error 0.05
|
—
|
|
Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
24 hours
|
36.78 °C
Standard Error 0.04
|
36.73 °C
Standard Error 0.04
|
—
|
|
Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
36 hours
|
36.55 °C
Standard Error 0.04
|
36.54 °C
Standard Error 0.04
|
—
|
|
Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
48 hours
|
36.34 °C
Standard Error 0.03
|
36.36 °C
Standard Error 0.03
|
—
|
|
Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
72 hours
|
36.30 °C
Standard Error 0.03
|
36.31 °C
Standard Error 0.03
|
—
|
|
Body Temperature at Each Time Point in Adults Randomized to Baloxavir or Oseltamivir
96 hours
|
36.26 °C
Standard Error 0.03
|
36.23 °C
Standard Error 0.03
|
—
|
SECONDARY outcome
Timeframe: Initiation of study treatment up to Day 14Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo whose symptom score at baseline was moderate (2) or severe (3) with available time to alleviation of symptoms data.
Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of each symptom was defined as the time from the start of treatment to the start of the time period when the individual symptom was assessed by the participant as 0 (None) or 1 (Mild) for a duration of at least 21.5 hours.
Outcome measures
| Measure |
Baloxavir
n=455 Participants
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.
|
Placebo
n=230 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo
Cough
|
38.3 hours
Interval 30.3 to 43.5
|
61.4 hours
Interval 44.8 to 69.5
|
—
|
|
Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo
Sore Throat
|
31.5 hours
Interval 27.3 to 39.2
|
40.5 hours
Interval 31.8 to 48.3
|
—
|
|
Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo
Headache
|
26.1 hours
Interval 22.9 to 29.8
|
37.9 hours
Interval 25.8 to 42.2
|
—
|
|
Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo
Nasal Congestion
|
31.8 hours
Interval 29.9 to 38.7
|
52.5 hours
Interval 41.5 to 62.7
|
—
|
|
Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo
Feverishness or chills
|
20.9 hours
Interval 20.0 to 21.9
|
25.8 hours
Interval 21.7 to 31.5
|
—
|
|
Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo
Muscle or joint pain
|
23.2 hours
Interval 21.4 to 26.3
|
31.3 hours
Interval 25.5 to 39.2
|
—
|
|
Time to Alleviation of Individual Symptoms in Participants Randomized to Baloxavir or Placebo
Fatigue
|
25.3 hours
Interval 22.0 to 29.2
|
40.5 hours
Interval 31.2 to 46.8
|
—
|
SECONDARY outcome
Timeframe: Initiation of study treatment up to Day 14Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, whose symptom score at baseline was moderate (2) or severe (3) with available time to alleviation of symptoms data.
Participants assessed the severity of seven influenza-associated symptoms (cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue) on a 4-point scale (with 0 indicating no symptoms, 1 mild symptoms, 2 moderate symptoms, and 3 severe symptoms). Time to alleviation of each symptom was defined as the time from the start of treatment to the start of the time period when the individual symptom was assessed by the participant as 0 (None) or 1 (Mild) for a duration of at least 21.5 hours.
Outcome measures
| Measure |
Baloxavir
n=375 Participants
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.
|
Placebo
n=377 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir
Cough
|
38.2 hours
Interval 30.3 to 43.4
|
31.4 hours
Interval 28.6 to 36.8
|
—
|
|
Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir
Sore Throat
|
32.1 hours
Interval 27.6 to 39.8
|
30.4 hours
Interval 25.0 to 43.9
|
—
|
|
Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir
Headache
|
26.9 hours
Interval 24.5 to 30.8
|
25.6 hours
Interval 21.9 to 30.4
|
—
|
|
Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir
Nasal Congestion
|
33.0 hours
Interval 30.5 to 40.4
|
31.3 hours
Interval 26.8 to 39.8
|
—
|
|
Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir
Feverishness or chills
|
21.0 hours
Interval 20.0 to 22.0
|
21.2 hours
Interval 20.3 to 22.0
|
—
|
|
Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir
Muscle or joint pain
|
23.3 hours
Interval 21.6 to 26.7
|
24.0 hours
Interval 21.6 to 27.1
|
—
|
|
Time to Alleviation of Individual Symptoms in Adults Randomized to Baloxavir or Oseltamivir
Fatigue
|
28.9 hours
Interval 23.2 to 30.5
|
26.6 hours
Interval 23.0 to 30.8
|
—
|
SECONDARY outcome
Timeframe: Initiation of study treatment up to Day 14Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo whose health status score at baseline was lower than the preinfluenza health status score and with available time to return to preinfluenza health status data.
Participants were asked to record their preinfluenza health status on a scale from 0 (worst possible health) to 10 (normal health \[for someone your age and your health condition\]), and their health status every day after initiation of study treatment on the same scale. Return to preinfluenza health status was defined as time from the initiation of the study treatment to the first time when the health status score was equal to or higher than the preinfluenza health status score. Time to return to preinfluenza health status was analyzed using KM methods; participants with a smaller number on the scale for health status by the last observation time point were censored at that time point.
Outcome measures
| Measure |
Baloxavir
n=378 Participants
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.
|
Placebo
n=190 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Time to Return to Preinfluenza Health Status in Participants Randomized to Baloxavir or Placebo
|
129.2 hours
Interval 122.1 to 152.3
|
168.8 hours
Interval 145.9 to 202.2
|
—
|
SECONDARY outcome
Timeframe: Initiation of study treatment up to Day 14Population: Participants in the intention-to-treat infection population, ≥ 20 years of age and assigned to baloxavir or oseltamivir, whose health status score at baseline was lower than the preinfluenza health status score and with available time to return to preinfluenza health status data.
Participants were asked to record their preinfluenza health status on a scale from 0 (worst possible health) to 10 (normal health \[for someone your age and your health condition\]), and their health status every day after initiation of study treatment on the same scale. Return to preinfluenza health status was defined as time from the initiation of the study treatment to the first time when the health status score was equal to or higher than the preinfluenza health status score. Time to return to preinfluenza health status was analyzed using KM methods; participants with a smaller number on the scale for health status by the last observation time point were censored at that time point.
Outcome measures
| Measure |
Baloxavir
n=314 Participants
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.
|
Placebo
n=308 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Time to Return to Preinfluenza Health Status in Adults Randomized to Baloxavir or Oseltamivir
|
127.8 hours
Interval 121.5 to 152.8
|
128.5 hours
Interval 122.8 to 151.0
|
—
|
SECONDARY outcome
Timeframe: Initiation of study treatment up to Day 14Population: Participants in the intention-to-treat infection population assigned to baloxavir or placebo
The percentage of participants who experienced each influenza-related complication (hospitalization, death, sinusitis, otitis media, bronchitis, and radiologically confirmed pneumonia) as an adverse event after the initiation of the study treatment.
Outcome measures
| Measure |
Baloxavir
n=456 Participants
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.
|
Placebo
n=231 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo
Any complication
|
3.5 percentage of participants
Interval 2.0 to 5.6
|
4.3 percentage of participants
Interval 2.1 to 7.8
|
—
|
|
Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo
Death
|
0 percentage of participants
Interval 0.0 to 0.8
|
0 percentage of participants
Interval 0.0 to 1.6
|
—
|
|
Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo
Hospitalization
|
0 percentage of participants
Interval 0.0 to 0.8
|
0 percentage of participants
Interval 0.0 to 1.6
|
—
|
|
Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo
Sinusitis
|
0.9 percentage of participants
Interval 0.2 to 2.2
|
0.9 percentage of participants
Interval 0.1 to 3.1
|
—
|
|
Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo
Otitis media
|
0.4 percentage of participants
Interval 0.1 to 1.6
|
0 percentage of participants
Interval 0.0 to 1.6
|
—
|
|
Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo
Bronchitis
|
2.0 percentage of participants
Interval 0.9 to 3.7
|
3.5 percentage of participants
Interval 1.5 to 6.7
|
—
|
|
Percentage of Participants With Influenza-related Complications in Participants Randomized to Baloxavir or Placebo
Pneumonia
|
0.4 percentage of participants
Interval 0.1 to 1.6
|
0.4 percentage of participants
Interval 0.0 to 2.4
|
—
|
SECONDARY outcome
Timeframe: Initiation of study treatment up to Day 14Population: Participants in the intention-to-treat infection population ≥ 20 years of age and assigned to baloxavir or oseltamivir.
The percentage of participants who experienced each influenza-related complication (hospitalization, death, sinusitis, otitis media, bronchitis, and radiologically confirmed pneumonia) as an adverse event after the initiation of the study treatment.
Outcome measures
| Measure |
Baloxavir
n=376 Participants
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.
|
Placebo
n=377 Participants
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.
|
Oseltamivir
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir
Any complication
|
4.0 percentage of participants
Interval 2.2 to 6.5
|
2.4 percentage of participants
Interval 1.1 to 4.5
|
—
|
|
Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir
Death
|
0 percentage of participants
Interval 0.0 to 1.0
|
0 percentage of participants
Interval 0.0 to 1.0
|
—
|
|
Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir
Hospitalization
|
0 percentage of participants
Interval 0.0 to 1.0
|
0.3 percentage of participants
Interval 0.0 to 1.5
|
—
|
|
Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir
Sinusitis
|
0.8 percentage of participants
Interval 0.2 to 2.3
|
0 percentage of participants
Interval 0.0 to 1.0
|
—
|
|
Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir
Otitis media
|
0.5 percentage of participants
Interval 0.1 to 1.9
|
0.3 percentage of participants
Interval 0.0 to 1.5
|
—
|
|
Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir
Bronchitis
|
2.4 percentage of participants
Interval 1.1 to 4.5
|
1.6 percentage of participants
Interval 0.6 to 3.4
|
—
|
|
Percentage of Participants With Influenza-related Complications in Adults Randomized to Baloxavir or Oseltamivir
Pneumonia
|
0.5 percentage of participants
Interval 0.1 to 1.9
|
0.3 percentage of participants
Interval 0.0 to 1.5
|
—
|
SECONDARY outcome
Timeframe: From first dose of study drug to Day 22Population: All participants who received at least 1 dose of study drug
Outcome measures
| Measure |
Baloxavir
n=610 Participants
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.
|
Placebo
n=309 Participants
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.
|
Oseltamivir
n=513 Participants
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Percentage of Participants With Adverse Events (AEs)
Adverse events (AEs)
|
20.7 percentage of participants
|
24.6 percentage of participants
|
24.8 percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs)
Serious adverse events (SAEs)
|
0.3 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs)
AEs leading to withdrawal of study drug
|
0.3 percentage of participants
|
0.3 percentage of participants
|
0.4 percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs)
Treatment-related adverse events (TRAEs)
|
4.4 percentage of participants
|
3.9 percentage of participants
|
8.4 percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs)
Treatment-related serious adverse events
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
|
Percentage of Participants With Adverse Events (AEs)
TRAEs leading to withdrawal of study drug
|
0.0 percentage of participants
|
0.3 percentage of participants
|
0.2 percentage of participants
|
Adverse Events
Baloxavir
Placebo
Oseltamivir
Serious adverse events
| Measure |
Baloxavir
n=610 participants at risk
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.
|
Placebo
n=309 participants at risk
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.
|
Oseltamivir
n=513 participants at risk
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Infections and infestations
Meningitis viral
|
0.16%
1/610 • From first dose of treatment to Day 22
|
0.00%
0/309 • From first dose of treatment to Day 22
|
0.00%
0/513 • From first dose of treatment to Day 22
|
|
Gastrointestinal disorders
Incarcerated inguinal hernia
|
0.16%
1/610 • From first dose of treatment to Day 22
|
0.00%
0/309 • From first dose of treatment to Day 22
|
0.00%
0/513 • From first dose of treatment to Day 22
|
Other adverse events
| Measure |
Baloxavir
n=610 participants at risk
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.
|
Placebo
n=309 participants at risk
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.
|
Oseltamivir
n=513 participants at risk
Participants aged 20 to 64 years received 75 mg oseltamivir orally BID on Days 1 to 5 and placebo to baloxavir on Day 1.
|
|---|---|---|---|
|
Infections and infestations
Bronchitis
|
2.6%
16/610 • From first dose of treatment to Day 22
|
5.5%
17/309 • From first dose of treatment to Day 22
|
3.5%
18/513 • From first dose of treatment to Day 22
|
|
Infections and infestations
Sinusitis
|
1.1%
7/610 • From first dose of treatment to Day 22
|
2.6%
8/309 • From first dose of treatment to Day 22
|
0.97%
5/513 • From first dose of treatment to Day 22
|
|
Gastrointestinal disorders
Diarrhoea
|
3.0%
18/610 • From first dose of treatment to Day 22
|
4.5%
14/309 • From first dose of treatment to Day 22
|
2.1%
11/513 • From first dose of treatment to Day 22
|
|
Gastrointestinal disorders
Nausea
|
1.3%
8/610 • From first dose of treatment to Day 22
|
1.3%
4/309 • From first dose of treatment to Day 22
|
3.1%
16/513 • From first dose of treatment to Day 22
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor can embargo results from a PI's center until the combined results from the completed study have been published in full or the sponsor confirms there will be no multicenter study publication. Results communications must be provided to the sponsor for review at least 60 days before submission for publication. By written request, the sponsor can extend the embargo up to an additional 60 days. The sponsor cannot require changes to scientific content and cannot further extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER