Safety and effectiveness of baloxavir marboxil for the treatment of influenza in Japanese clinical practice: A postmarketing surveillance of more than 3000 patients

Nakazawa, Masami; Hara, Kanae; Komeda, Takuji; Ogura, Eriko

doi:10.1016/j.jiac.2020.04.014

Cited by 15 publications

(7 citation statements)

References 13 publications

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“…Findings from the two open-label noncomparative studies of weight-adjusted baloxavir suggest that baloxavir is likely to be clinically effective compared with NAIs in Japanese children aged 6 to < 12 years [ 27 , 28 ]. In both studies, there was a rapid reduction in virus titer, and the median TTIA was 45 h. Gastrointestinal events were the most commonly reported AEs in both studies, which is consistent with the findings in non-Japanese children in miniSTONE-2 [ 24 ] and with the findings from a large postmarketing surveillance study of baloxavir in Japan that included 896 children aged < 12 years [ 29 ]. In this surveillance study, adverse drug reactions occurred more frequently in children than in adults, but diarrhea was the most common adverse reaction in all age groups.…”

Section: Discussionsupporting

confidence: 85%

“…Two open-label noncomparative studies in Japanese children have been conducted, which showed that a single weight-adjusted dose of baloxavir granules [ 27 ] or tablet (in accordance with the approved dose regimen) [ 28 ] is well tolerated and appears to be clinically and virologically effective. In addition, findings from a large postmarketing surveillance study enrolling more than 3000 patients in Japan showed that the median time to alleviation of influenza symptoms in the pediatric population aged 6 to < 12 years of age (n = 703), was similar to that in adults [ 29 ]. However, no randomized active-controlled studies comparing baloxavir with oseltamivir have been conducted in a Japanese pediatric population at the Japanese approved dose of baloxavir.…”

Section: Introductionmentioning

confidence: 99%

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Clinical and virological outcomes with baloxavir compared with oseltamivir in pediatric patients aged 6 to < 12 years with influenza: an open-label, randomized, active-controlled trial protocol

et al. 2021

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Background Children with influenza virus infections are prone to complications and are common sources of influenza transmission. Baloxavir marboxil inhibits cap-dependent endonuclease and was approved for influenza treatment in adolescent, adult, and pediatric patients in Japan. The miniSTONE-2 study included pediatric patients with influenza (1 to < 12 years) and demonstrated similar median times to alleviation of signs and symptoms of influenza with a single dose of baloxavir granules (weight < 20 kg: 2 mg/kg, ≥ 20 kg: 40 mg) and oseltamivir. Although the baloxavir dose in miniSTONE-2 was higher than the Japanese-approved dose, baloxavir exposure in miniSTONE-2 was similar to Japanese pediatric patients who receive the Japanese-approved dose. This study will be the first randomized active-controlled study in pediatric patients with influenza using the Japanese-approved dose of baloxavir. Methods This is a multicenter, open-label, randomized, active-controlled trial in which 200 Japanese subjects aged 6 to < 12 years with influenza virus infection are randomly allocated (2:1) to a single dose of baloxavir at the approved dose in Japan (weight ≥ 10 to < 20 kg: 10 mg, ≥ 20 to < 40 kg: 20 mg, ≥ 40 kg: 40 mg) or oseltamivir twice daily for 5 days. The primary clinical endpoint is the time to illness alleviation of influenza, from administration of baloxavir or oseltamivir until the following criteria were met and sustained for at least 21.5 h (24 h—10%): cough and nasal discharge/nasal congestion rated as absent or mild axillary body temperature < 37.5 °C. The primary analysis population is the intention-to-treat infected population, which includes all pediatric subjects who receive at least one dose of study drug and have confirmed influenza virus infection by reverse transcription-polymerase chain reaction. The safety population includes all subjects who receive at least one dose of study drug. Discussion No comparative studies have been conducted to confirm the efficacy and safety of baloxavir versus a comparator in pediatric patients with influenza infection in Japan. The outcomes from this trial will provide evidence on the efficacy and safety of baloxavir as an antiviral treatment option for Japanese pediatric patients with influenza infection. Trial registration Japan Registry of Clinical Trials: jRCTs011200011. Registered November 2020. (https://rctportal.niph.go.jp/en/).

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Clinical and virological outcomes with baloxavir compared with oseltamivir in pediatric patients aged 6 to < 12 years with influenza: an open-label, randomized, active-controlled trial protocol

et al. 2021

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“…The mean numbers of days until fever resolution (approximately 2 days) and until returning to normal life (approximately 5 days) from the initiation of the antivirals are reasonable when considering previous reports as well as regulation in Japan. Although a significant difference was observed among types of influenza viruses, the number of days until fever resolution is reportedly within 2 days from treatment initiation for Japanese pediatric patients, regardless of the type of antiviral [19][20][21]. Students developing influenza are suspended from school for 5 days after the onset of influenza and 2 days (or 3 days for infants) after fever resolution [22,23].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Inconvenience Costs Between Influenza Antivirals for Japanese Pediatric Patients: A Conjoint Analysis of Parental Responses

et al. 2022

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Introduction: Certain drug characteristics, including dosage and form, are associated with either convenience or inconvenience for the patients taking them, and any inconvenience can be considered as a ''cost'' in disease treatment. Multiple antivirals are available for influenza in Japan, with various dosages and forms. This study evaluated the inconvenience costs associated with influenza antivirals for pediatric patients by using conjoint analysis on responses from their parents. Methods: An online survey (May 2021) was conducted for parents whose child took antivirals for influenza at 6-11 years during the 3 years until March 2021. Attributes of the

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“…Subgroup analyses of Asian patients (mostly Japanese) in pivotal phase III studies show that, compared with placebo, baloxavir marboxil results in significantly shorter time to alleviation of symptoms (TTAS; CAPSTONE‐1: 80.2 h vs. 53.7 h and CAPSTONE‐2: 102.8 h vs. 77.0 h, respectively) and time to cessation of viral shedding (CAPSTONE‐1: 96 h vs. 24 h and CAPSTONE‐2: 96 h vs. 48 h, respectively) in otherwise healthy (OwH) and high‐risk (HR) patients 9,11,13 . Moreover, postmarketing surveillance of over 3000 patients across 688 hospitals in Japan indicate that baloxavir marboxil, administered per recommended dosing, is well‐tolerated and efficacious in the treatment of influenza A and B 14 . However, there are no clinical data in Chinese populations.…”

Section: Introductionmentioning

confidence: 99%

“… 9 , 11 , 13 Moreover, postmarketing surveillance of over 3000 patients across 688 hospitals in Japan indicate that baloxavir marboxil, administered per recommended dosing, is well‐tolerated and efficacious in the treatment of influenza A and B. 14 However, there are no clinical data in Chinese populations.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics, safety, and simulated efficacy of an influenza treatment, baloxavir marboxil, in Chinese individuals

Liu

Retout

Duval³

et al. 2022

Clinical Translational Sci

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Baloxavir marboxil is an endonuclease inhibitor indicated for the treatment of influenza in patients ≥12 years. No data exist for Chinese patients in global studies. This randomized, open-label, phase I study evaluated the pharmacokinetics (PK) and safety of baloxavir marboxil in healthy Chinese volunteers and was used to anticipate efficacy in Chinese patients. Patients received a single oral dose of baloxavir marboxil (40 or 80 mg [1:1]). Serial blood samples were collected predose and at various timepoints up to 14 days postdose. Baloxavir marboxil and acid plasma concentrations were determined by liquid chromatography tandem mass spectrometry. PK parameters of baloxavir acid were estimated by noncompartmental analysis. Adverse events (AEs) were recorded. Time to alleviation of symptoms (TTAS) was simulated for otherwise healthy (OwH) and high-risk (HR) Chinese and Asian patients. Thirty-two male patients received baloxavir marboxil. Baloxavir acid plasma concentration peaked 4 h postdose. Mean maximum concentration (C max ) was 107.6 and 206.9 ng/ml, and mean area under the plasma concentration-time curve from zero to infinity (AUC 0-inf ) was 6955 and 9643 ng•h/ml in the 40 and 80 mg cohorts, respectively. AEs were mild and transient; no new safety signals were identified. Simulated median TTAS for OwH and HR Chinese patients agreed with simulated values in Asian patients. PK parameters were similar to Asian populations in other studies. The globally adopted baloxavir marboxil dosing strategy was consistent with the established safety profile of baloxavir marboxil in this population. Simulated efficacy indicated Chinese patients could benefit from similar efficacy to Asian patients. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?Baloxavir marboxil, the prodrug of baloxavir acid, is indicated for the treatment of influenza virus infection and is to be administered within 48 h of symptom onset. At the time of this study, baloxavir marboxil was not approved for the

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Safety and effectiveness of baloxavir marboxil for the treatment of influenza in Japanese clinical practice: A postmarketing surveillance of more than 3000 patients

Cited by 15 publications

References 13 publications

Clinical and virological outcomes with baloxavir compared with oseltamivir in pediatric patients aged 6 to < 12 years with influenza: an open-label, randomized, active-controlled trial protocol

Clinical and virological outcomes with baloxavir compared with oseltamivir in pediatric patients aged 6 to < 12 years with influenza: an open-label, randomized, active-controlled trial protocol

Comparison of Inconvenience Costs Between Influenza Antivirals for Japanese Pediatric Patients: A Conjoint Analysis of Parental Responses

Pharmacokinetics, safety, and simulated efficacy of an influenza treatment, baloxavir marboxil, in Chinese individuals

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