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Randomized, Open-label, Active Controlled Trial of Baloxavir Malboxil in Pediatric Patients with Influenza Infection Aged 6 to 11 Years

open-label, active-controlled study of baloxavir in pediatric patients with influenza

199

A total of 211 patients were enrolled in this study, and excluding 12 screen failures, 199 patients were randomized. The 199 patients were randomized to the baloxavir group and oseltamivir group in a 2:1 ratio by dynamic allocation using the minimization method with age (6<= and <9, 9<= and <12 years old) and influenza composite symptom score for cough and nasal mucus/congestion (<=3, 4<= points) as allocation factors, and 131 were assigned to the baloxavir group and 68 were assigned to the oseltamivir group. Of the randomized 199 patients, 195 (baloxavir group: 128, oseltamivir group: 67) were included in the ITTI population, excluding 4 due to no administration of the study drug (1 in the baloxavir group), and unconfirmed infection with influenza virus (baloxavir group: 2, oseltamivir group: 1). Of the randomized 199 patients, 198 were included in the safety analysis population, excluding 1 in the baloxavir group due to no administration of the study drug. 1 patient who was randomized to the baloxavir group but mistakenly given oseltamivir was analyzed as the oseltamivir group in the safety analysis, and the safety analysis population consisted of 129 in the baloxavir actual administration group and 69 in the oseltamivir actual administration group. There was no clear difference in the distribution of background information of the 195 ITTI patients (baloxavir group: 128, oseltamivir group: 67) between these groups. The details of the main background variables were as follows: The mean age (SD: standard deviation) was 9.0 (1.6) years in the baloxavir group and 9.0 (1.6) years in the oseltamivir group, and there were 66 (51.6%) and 38 (56.7%) males, and 62 (48.4%) and 29 (43.3%) females, respectively. The number of patients with a history of influenza infection were 82 (64.1%) in the baloxavir group and 40 (59.7%) in the oseltamivir group. The number of patients who had received pretreatment medications as symptomatic therapy within 2 days before study treatment was 28 (21.9%) and 19 (28.4%) in the baloxavir and oseltamivir group, respectively, and the number of patients who had received pretreatment was 1 (0.8%) and 1 (1.5%) in each group. The mean temperature (SD) was 38.77 (0.52) and 38.63 (0.57) degrees celsius in the baloxavir and oseltamivir group, respectively. Regarding the period between the onset of influenza symptoms and the screening of this study, the number of patients in the baloxavir and oseltamivir groups were as follows: 0 to 12 hours, 27 (21.1%) and 23 (34.3%); 12 to 24 hours, 64 (50.0%) and 26 (38.8%); 24 to 36 hours, 25 (19.5%) and 14 (20.9%); 36 to 48 hours, 12 (9.4%) and 4 (6.0%), respectively. The number of patients who had influenza vaccination was 26 (20.3%) and 18 (26.9%) in the baloxavir and oseltamivir groups, respectively. The types/subtypes of influenza virus were as follows: A/H1N1pdm with 13 (10.2%) in the baloxavir group and 7 (10.4%) in the oseltamivir group; A/H3 with 64 (50.0%) and 35 (52.2%); A/Unknown with 1 (1.5%) in the oseltamivir group; B with 50 (39.1%) and 23 (34.3%); mixed infection of A/H1N1pdm and A/H3 with 1 (0.8%) in the baloxavir group; and mixed infection of A/H3NX and B with 1 (1.5%) in the oseltamivir group. The serum antibody titer for influenza virus were as follows: less than 10-fold with 84 patients (65.6%) in the baloxavir group and 37 patients (55.2%) in the oseltamivir group; 10-fold with 35 patients (27.3%) and 22 patients (32.8%); 20-fold with 7 patients (5.5%) and 3 patients (4.5%); 40-fold with 2 patients (1.6%) and 4 patients (6.0%); and 320-fold with 0 patients (0.0%) and 1 patient (1.5%). The mean total influenza composite symptom scores for cough and nasal mucus/congestion scores (SD) at the time of randomization were 3.5 (1.0) and 3.5 (0.8) in the baloxavir and oseltamivir group, respectively.

Of the randomized 199 patients (baloxavir group: 131, oseltamivir group: 68), 4 (3.1%) and 2 (2.9%) patients in each group discontinued the study, and 127 (96.9%) and 66 (97.1%) in each group completed the study. The mean study treatment duration (minimum, maximum) in the 195 ITTI population was 1.0 (1, 5) days for 128 patients in the baloxavir group and 5.3 (3, 6) days for 67 patients in the oseltamivir group. Medication compliance (SD) was 100.00% in the baloxavir group and 98.96 (3.54%) in the oseltamivir group. Concomitant medications were used in 118 (92.2%) and 63 (94.0%) in the baloxavir and oseltamivir group, respectively. The common concomitant medications used in the baloxavir group were acetaminophen in 85 (66.4%) patients, L-carbocysteine in 51 (39.8%) patients, ambroxol hydrochloride in 37 (28.9%) patients, and dextromethorphan hydrobromide hydrate in 27 (21.1%) patients. While in the oseltamivir group, the common concomitant medications were acetaminophen in 47 (70.1%) patients, L-carbocysteine in 31 (46.3%) patients, ambroxol hydrochloride in 27 (40.3%) patients, tranexamic acid in 16 (23.9%) patients, and dextromethorphan hydrobromide hydrate in 14 (20.9%) patients. The proportion of patients treated with ambroxol hydrochloride in the oseltamivir group was slightly higher than that in the baloxavir group, whilethere were no clear differences in the proportions of patients treated with other concomitant medications between these groups. For concomitant therapy, treatment with nebulizer was performed to 3 (2.3%) patients in the baloxavir group and 2 (3.0%) patients in the oseltamivir group.

In the safety analysis population of the 198 patients (129 patients in baloxavir actual administration group and: 69 patients in oseltamivir actual administration group), 25 adverse events (AEs) occurred in 23 (17.8%) patients in the baloxavir group, and 7 AEs occurred in 7 (10.1%) patients in the oseltamivir group. Among these, 12 AEs in 12 (9.3%) patients and 1 AE in 1 (1.4%) patient were adverse drug reaction (ADR) in each group. In addition to ADRs, 2 AEs for which a causal relationship to this study could not be denied were occurred in 2 patients in the baloxavir actual administration group. Consequently, the occurrence of AEs for which a causal relationship to this study could not be denied was 14 in 14 patients (10.9%) in the baloxavir actual administration group, and 1 in 1 patient (1.4%) in the oseltamivir actual administration group. There were no serious adverse events including deaths and no discontinuation of study treatment due to AEs in either group. Regarding the incidence of AEs in the baloxavir group, diarrhea was occurred in 4 (3.1%), epistaxis was in 3 (2.3%) patients, sinusitis, vomiting, and urticaria were in 2 (1.6%), respectively, and gastroenteritis, nasopharyngitis, bacterial pharyngitis, bacterial tonsillitis, abnormal behavior, asthma, cough variant asthma, constipation, drug rash, eczema, decreased platelet count, and urinary occult blood were in 1 (0.8%), respectively. In the oseltamivir group, vomiting was occurred in 2 (2.9%) patients, bacterial pharyngitis, infectious croup, adenovirus infection, erythema multiforme, and fever were occurred in 1 (1.4%), respectively. Among these, ADRs in the baloxavir group were diarrhea in 4 (3.1%) patients, vomiting in 2 (1.6%) patient, epistaxis, drug rash, eczema, urticaria, decreased platelet count, and urinary occult blood in 1 (0.8%) patient, respectively, in the oseltamivir group, erythema multiforme in 1 (1.4%) patient. Regarding timing of AE onset after the study treatment, 1-7 days was 20 (15.5%) and 7 (10.1%) patients in the baloxabir and oseltamivir group, respectively, and 8-14 days was 3 (2.3%) patients in the baloxavir group. AEs occurred in 8-14 days after the study treatment included sinusitis, gastroenteritis, nasopharyngitis, and asthma, each in 1 (0.8%) patient, and all other AEs occurred 1-7 days after study treatment. All timing of onset of the above-mentioned ADRs in the baloxavir group (12 [9.3%] patients) and in the oseltamivir group (1 [1.4%] patient) were 1-7 days after the study treatment. The outcomes of the AEs were recovered in 21 (16.3%) patients in the baloxavir group and 6 (8.7%) patients in the oseltamivir group, recovering in 2 (1.6%) patients and 1 (1.4%) patient respectively, and there were no patients who were not recovered, had sequelae, or died. The outcomes of all ADRs were recovered. The severity of AEs was Grade 2 in 11 (8.5%) patients in the baloxavir group and 4 (5.8%) patients in the oseltamivir group, Grade 1 was 12 (9.3%) patients and 3 (4.3%) patients, respectively, and there were no AEs of Grade 3- 5. Grade 2 AEs in the baloxavir group included sinusitis and diarrhea each in 2 (1.6%) patients, and gastroenteritis, bacterial tonsillitis, asthma, constipation, urticaria, drug rash, and eczema, each in 1 (0.8%) patient, and in the oseltamivir group, infectious croup, adenovirus infection, erythema multiforme, and fever were reported each in 1 (1.4%) patient. Among these, Grade 2 ADRs were diarrhea in 2 (1.6%) patients, drug rash and eczema each in 1 (0.8%) patient, in the baloxavir group, and erythema multiforme in 1 (1.4%) patient in the oseltamivir group.

1) Primary endpoint The median time (95%CI) to disappearance of influenza symptoms in the ITTI population with Kaplan-Meier method was 44.8 (41.5, 69.7) hours in the baloxavir group and 72.2 (50.9, 96.9) hours in the oseltamivir group, with a median difference (95%CI) of -27.4 (-52.7, 6.5) hours, which was the baloxavir group had a shorter time. The restricted mean survival time (RMST) (95%CI) in day 8 (192 hours) was 74.3 (63.9, 84.8) hours in the baloxavir group and 86.6 (72.3, 100.9) hours in the oseltamivir group, with a difference in RMST (95%CI) of -12.3 (-30.0, 5.4) hours. 2) Secondary endpoints In the ITTI population, the median time (95%CI) to continuous disappearance of influenza symptoms was 67.1 (44.1, 90.5) hours in the baloxavir group and 89.9 (64.7, 113.0) hours in the oseltamivir group, with a median difference (95%CI) of -22.8 (-52.7, 16.1) hours. The RMST (95%CI) in day 8 (192 hours) was 88.3 (76.4, 100.3) hours in the baloxavir group and 102.1 (85.6, 118.5) hours in the oseltamivir group, with a difference in RMST (95%CI) of -13.8 (-34.1, 6.6) hours. The median time (95% CI) to return to normal temperature was 22.0 (20.5, 24.5) hours in the baloxavir group and 23.1 (18.0, 26.9) hours in the oseltamivir group. The median difference between groups was -1.1 (-5.6, 4.6) hours. The median time (95% CI) to continuous return to normal temperature was 22.8 (20.6, 25.5) hours in the baloxavir group and 26.0 (20.2, 34.4) hours in the oseltamivir group. The median difference between groups was -3.2 (-12.1, 3.3) hours. The proportion of patients (95% CI) with fever reduction after the start of study treatment increased in both groups, reaching 46.3% (37.2, 55.6) in the baloxavir group and 58.9% (45.0, 71.9) in the oseltamivir group at 18 hours after the treatment. The proportion of patients (95% CI) with fever reduction at 24 hours (Day 2) after the treatment further increased to 70.4% (61.2, 78.6) in the baloxavir group and slightly increased to 61.7% (48.2, 73.9) in the oseltamivir group. After 36 hours of the treatment, the fever reduction rates changed similar in both groups. The mean temperature (SD) at each evaluation point was 38.77 (0.52) degrees in the baloxavir group and 38.63 (0.57) degrees in the oseltamivir group before the study treatment (Day 1). On Day 2, the temperature was 37.20 (0.69) degrees in the baloxavir group and 37.36 (0.86) degrees in the oseltamivir group, and both groups showed a decrease. The mean temperature (SD) in both groups continued to decrease, remaining below 36.5 degrees from Day 4 (36.46 (0.32) degrees) onwards in the baloxavir group and from Day 5 (36.50 (0.37) degrees) onwards in the oseltamivir group. The median time to disappearance of seven influenza symptoms (cough, sore throat, headache, runny nose/stuffy nose, fever or chills, muscle or joint pain, and fatigue) was 49.0 hours in the baloxavir group and could not be calculated in the oseltamivir group. The median time (95% CI) for the disappearance of each influenza symptom was as follows: for cough, it was 27.3 (20.9, 43.7) hours in the baloxavir group and 45.6 (22.8, 60.4) hours in the oseltamivir group, with a median difference between groups (95% CI) of -18.3 (-33.6, 9.2) hours. For sore throat, there was no disappearance observed in the one evaluable patient in the oseltamivir group. For headache, the median disappearance time in the two evaluable patients in the baloxavir group was 29.7 hours. For runny nose/stuffy nose, it was 30.8 (23.7, 45.0) hours in the baloxavir group and 43.5 (24.9, 65.1) hours in the oseltamivir group, with a median difference between groups (95% CI) of -12.8 (-37.8, 15.8) hours. For fever or chills, it was 12.5 hours in the three evaluable patients in the baloxavir group and 13.5 hours in the one patient in the oseltamivir group. For fatigue, the median disappearance time in the two evaluable patients in the oseltamivir group was 62.5 hours. Influenza-related complications observed after the start of study treatment included sinusitis in 2 patients (1.6%) in the baloxavir group and bronchitis in 1 patient (1.5%) in the oseltamivir group. No influenza-related complications specific to pediatric patients were observed. After the start of the study treatment, systemic antibiotics for influenza-related complications were given to 2 patients (1.6%) only in the baloxavir group. [Virological evaluation] The mean viral titer (SD) at each evaluation point was as follows: before the study treatment (Day 1), it was 6.00 (1.71) log10 TCID50/mL in the baloxavir group and 5.67 (1.92) log10 TCID50/mL in the oseltamivir group. On Day 2, the titers decreased in both groups to 1.28 (1.06) log10 TCID50/mL and 3.68 (2.04) log10 TCID50/mL, respectively, with the baloxavir group showing a lower mean viral titer. On Day 5, the titers were nearly the same in both groups, at 1.49 (1.32) log10 TCID50/mL and 1.65 (1.59) log10 TCID50/mL, respectively. On Day 10, the titers were 0.76 (0.32) log10 TCID50/mL in the baloxavir group and 0.77 (0.34) log10 TCID50/mL in the oseltamivir group. The mean change in viral titer (SD) on Day 2 was -4.72 (1.96) log10 TCID50/mL in the baloxavir group and -2.05 (2.35) log10 TCID50/mL in the oseltamivir group, with a greater change observed in the baloxavir group. On Day 5, the changes were similar in both groups, at -4.49 (2.39) log10 TCID50/mL and -4.11 (1.94) log10 TCID50/mL, respectively. On Day 10, the mean change (SD) was even greater compared to Day 5 in both groups, at -5.20 (1.74) log10 TCID50/mL and -5.00 (1.77) log10 TCID50/mL, respectively. The proportion of patients (95% CI) with positive viral titers after the start of study treatment was as follows: on Day 2, 47.2% (38.3, 56.3) in the baloxavir group and 93.8% (85.0, 98.3) in the oseltamivir group. The difference between groups (95% CI) was -46.6% (-59.4, -32.7), indicating that the baloxavir group had a lower proportion than the oseltamivir group. On Day 5, the proportions were 45.2% (36.4, 54.3) for the baloxavir group and 50.8% (37.9, 63.6) for the oseltamivir group, with a group difference (95% CI) of -5.6% (-20.9, 9.9). On Day 10, the proportions largely decreased in both groups to 6.8% (3.0, 13.0) for the baloxavir group and 11.7% (4.8, 22.6) for the oseltamivir group, with a group difference (95% CI) of -4.8% (-20.4, 10.6). The proportion of patients (95% CI) with positive viral RNA after the start of study treatment was as follows: on Day 2, 99.2% (95.7, 100.0) in the baloxavir group and 97.0% (89.6, 99.6) in the oseltamivir group, with a group difference (95% CI) of 2.2% (-12.6, 17.0). On Day 5, the proportions were 92.9% (86.9, 96.7) for the baloxavir group and 84.6% (73.5, 92.4) for the oseltamivir group, with a group difference (95% CI) of 8.2% (-6.9, 23.1). On Day 10, the proportions largely decreased in both groups to 46.2% (36.9, 55.6) for the baloxavir group and 48.4% (35.5, 61.4) for the oseltamivir group, with a group difference (95% CI) of -2.2% (-17.6, 13.1). The median time (95% CI) to initial cessation of viral shedding was 48.0 hours (48.0, 96.0) in the baloxavir group and 192.0 hours (120.0, 192.0) in the oseltamivir group, with a median difference (95% CI) of -144.0 hours (-144.0, -48.0), indicating a shorter time in the baloxavir group compared to the oseltamivir group. The median time (95% CI) to sustained cessation of viral shedding was 120.0 hours (96.0, 192.0) in the baloxavir group and 192.0 hours (120.0, 216.0) in the oseltamivir group, with a median difference (95% CI) of -72.0 hours (-96.0, 48.0).

The efficacy and safety of a single dose of baloxavir was compared with that of oseltamivir administered twice daily for five days in pediatric patients aged 6<= and <12 years. The median time until disappearance of influenza symptoms, the primary endpoint, was shorter in the baloxavir group than the oseltamivir group. There were no clear differences between these groups in other variables related to influenza symptoms. No safety concerns were reported in either group.

Nov. 19, 2024

Yes

De-identified (anonymized) or coded (pseudonymized) individual clinical trial participant data would be shared when needed, upon request from researchers, authorized by the representative investigator of this study.

https://jrct.mhlw.go.jp/latest-detail/jRCTs011200011

Ishiguro Nobuhisa

Hokkaido University Hospital

Kita-14, Nishi-5, Kita-ku, Sapporo, Hokkaido

nishigur@med.hokudai.ac.jp

Ishiguro Nobuhisa

Hokkaido University Hospital

Kita-14, Nishi-5, Kita-ku, Sapporo, Hokkaido

+81-11-706-5703

nishigur@med.hokudai.ac.jp

Complete

Nov. 20, 2020

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

Patients meeting all of the following criteria are selected.
1) A patient who have provided written consent to participate in clinical research from a proxy consenter.
2) Male or female patients aged 6 to 11 years at the time of acquisition of the Ascent according to consent and age.
3) Patients who met all of the following criteria and were diagnosed with influenza virus infection.
- Fever is more than 38 degrees (axillary temperature) at screening
- In patients aged 6 to 11 years; at least one of respiratory symptoms (cough, nasal discharge/nasal congestion) associated with influenza virus infection are present with a severity of moderate or greater.
- Positive rapid influenza diagnostic test (RIDT) with nasal swab, nasal aspirate, throat swab, or nasal drip (Other appropriate samples) or positive by an influenza test method covered by insurance, such as telescope for endoscopy.
4) Patients within 48 hours of onset (At the time of screening). However, onset is defined as the first confirmed fever of 37.5 degree centigrade or higher.
5) Patients judged by the investigator or subinvestigator (Investigators, etc.) to be able to take (swallowing) Baloxavir tablets and Oseltamivir capsules,tablets or dry syrup.
6) A parent/guardian who is willing and able to comply with the research requirements at the discretion of the investigator, etc.
7) Patients who are able to comply with the study requirements, depending on their level of understanding.
8) Patients who weigh 10 kg or more at screening.

Patients who meet any of the following criteria are excluded:.
1) Patients with severe symptoms due to influenza virus infection who are considered to require inpatient treatment.
2) Patients with chronic respiratory disease including uncontrolled bronchial asthma.
3) Patients with hepatitis/cirrhosis.
4) Patients with neurological disorders and neurodevelopmental disorders (Including brain, spinal, peripheral, and muscle disorders).
5) Patients with endocrine disorders (Diabetes, thyroid disease, adrenal gland abnormalities, etc.).
6) Patients with heart disease (Congenital heart disease, congestive heart failure, coronary artery disease, etc., excluding patients with hypertension only) during drug therapy.
7) Patients receiving systemic corticosteroids or immunosuppressive therapy.
8) Patients with primary immunodeficiency syndrome.
9) Patients with severe renal impairment (CCr: more than 30 (mL/min) or eGFR more than 30 (mL/min/1.73 m2)).
10) Patients with human immunodeficiency virus (HIV) infection.
11) Patients with malignancy within the past 5 years
12) Patients with consciousness disturbed, abnormal behavior * (Sudden start, jump, or other unexpected behavior that, if not stopped, may affect life) or convulsions at the time of screening, or those complicated by encephalitis or encephalopathy.
*"Nationwide trend research on abnormal behavior during influenza-like illness"
13) Patients with a history of encephalitis/encephalopathy, epilepsy not controlled with antiepileptic drugs, or abnormal behavior associated with influenza virus infection * (Sudden start, jump, or other unexpected behavior that, if not stopped, may affect life) within the past 2 years.
*"Nationwide trend research on abnormal behavior during influenza-like illness"
14) Patients with infections requiring systemic antimicrobial therapy and/or antiviral (Exclude anti-influenza drugs) therapy at screening.
15) Patients judged by the investigator etc. to require the use of prohibited concomitant drugs during the study period.
16)Patients who received valoxavir (Zofruza), peramivir (RAPIACTA), raninamivir (Inaville), oseltamivir (Tamiflu), zanamivir (Relenza), or amantadine (Simmetrel) within 30 days before screening.
17) Patients with allergies to anti-influenza virus drugs and/or acetaminophen and/or a history of clinically relevant intolerance.
18) Patients with SARS-CoV -2 positivity or suspected COVID-19.
(The SARS-CoV -2 rapid diagnostic test should be performed according to the New Coronavirus Infection COVID-19 Clinical Practice Guide (Medical Guide Review Committee) and negative for SARS-CoV -2 at entry.)
19) Patients with a severe underlying disorder that may affect evaluation.
20) Patients who have difficulty drawing blood from veins.
21) Patients person who have received the study drug or unapproved drug for 30 days or has not passed 5 times the half-life at the time of screening.
22) Patients with a disease or condition determined by the investigator, etc. to be difficult to ensure patient safety or the quality of the study data.
23) Patients judged to be inappropriate to participate in the clinical study by the investigator, etc.
24) A post-menarche female patient who wishes to become pregnant during pregnancy or during a clinical study. Or a lactating woman.

Both

influenza

Patients with a positive by a rapid influenza diagnostic test (RIDT) or by an influenza test method covered by insurance, such as telescope for endoscopy and moderate or severe influenza symptoms and a negative SARS-CoV -2 test are randomly assigned to receive a single dose of baloxavir or oseltamivir, and the baloxavir group is to receive a single dose of baloxavir and the oseltamivir group is to receive oseltamivir 2 times daily for 5 days.

influenza, human

D007251

Time to alleviation of symptom

1) Time to continuous resolution of influenza symptoms (Cough, "Nasal discharge/nasal congestion", "body temperature") (last at least 72 hours)
- It is defined as the time from the start of administration of the test drug until the symptoms of influenza disappear. Resolution of symptoms is defined as the time point of resolution of influenza symptoms when cough and "Nasal discharge/nasal congestion" are assessed as 0 (None) or 1 (mild) and the clinical condition of the more than 37.5 degrees body temperature has been maintained for at least 72 hours.
2) Time to return to normal temperature (last at least 12 hours)
- It is defined as the time from the start of the test drug administration to normal temperature (more than 37.5 degrees). Recovery to normal body temperature is defined as the time to return to normal body temperature if the subject's self-measured body temperature falls below 37.5 degrees and has been present for at least 12 hours.
3) Time to continuous return to normal temperature (last at least 72 hours)
- It is defined as the time from the start of the test drug administration to normal temperature (more than 37.5 degrees). Recovery to normal body temperature is the time to return to normal body temperature if the subject's self-measured body temperature falls below 37.5 degrees and has been present for at least 72 hours.
4) Whether pyrexia was resolved to normal more than 37.5 degrees at each time point
- Percentage of patients with a temperature more than 37.5 degrees at each time point.
5) Body temperature at each time point
- At each time point, the mean and 95 percentage confidence intervals for body temperature in each treatment group and the between-group difference in mean body temperature and its 95 percentage confidence interval should be calculated.
6) Time to resolution of 7 symptoms of influenza (Cough, "sore throat", "headache", "Nasal discharge/nasal congestion", "Fever or chills", "Pain in muscles or joints", "tiredness")
- It is defined as the time from the start of administration of the test drug until the symptoms of influenza 7 symptoms disappear. The elimination of influenza symptoms is defined as the time point when all 7 influenza symptoms are evaluated as 0 (None) or 1 (mild), and if the state has been maintained for at least 21.5 hours, the time point when the 7 influenza symptoms are eliminated is defined as the time point when the 7 influenza symptoms are eliminated.
7) Time to resolution of each influenza symptom
- It is defined as the time from the start of administration of the test drug until each influenza symptom disappears. The elimination of influenza symptoms is defined as the time point at which each influenza symptom (Cough, "sore throat", "headache", "Nasal discharge/nasal congestion", "Fever or chills", "Pain in muscles or joints", "tiredness") is evaluated to be 0 (None) or 1 (mild), and if the state has been maintained for at least 21.5 hours, the time point at which each symptom is eliminated is defined as the time point at which each symptom is eliminated.
8) Presence or absence of flu-related complications (Radiographically confirmed pneumonia, bronchitis, sinusitis, and otitis media)
- It is defined as the percentage of study subjects who developed any flu-related complication (Sinusitis, otitis media, bronchitis, and radiographically confirmed pneumonia) after the start of treatment with the study drug and the percentage of study subjects who developed each flu-related complication.
9) Presence or absence of influenza-related complications unique to pediatric patients (Influenza encephalitis or encephalopathy, febrile convulsion, myositis)
- It is defined as the percentage of study subjects who developed any pediatric patient-specific flu-related complication (Influenza encephalitis or encephalopathy, febrile convulsion, myositis) after the start of study drug administration and the percentage of study subjects who developed each pediatric patient-specific flu-related complication.
10) Death or hospitalization due to influenza-related complications and influenza-related complications unique to pediatric patients
- It is defined as the proportion of research subjects who died or were hospitalized due to influenza-related complications after the start of study drug administration, the proportion of research subjects who died, and the proportion of research subjects who were hospitalized.
11) Use or nonuse of antibiotics
- Defined as the percentage of study subjects who received systemic antibiotics for infections secondary to influenza virus infection after the start of study drug administration.

+81-11-706-7934

Oct. 22, 2020

none