Open-label study of the safety, pharmacokinetics, and effectiveness of a 2 mg/kg dose of baloxavir marboxil 2% granules in children <20 kg with influenza. Issue 8 (August 2021)

• Record Type: Journal Article
• Authors: Sonoyama, Takuhiro; Sakaguchi, Hiroki; Koshimichi, Hiroki; Noshi, Takeshi; Tsuchiya, Kenji; Uehara, Takeki
• Is Part Of: Journal of infection and chemotherapy. Volume 27:Issue 8(2021)
• Page Start: 1223
• Page End: 1229
• Publication Date: 2021-08
• Subjects: Baloxavir -- Child -- Influenza -- Human -- Pharmacokinetics; AE adverse event -- C24 concentration 24 hours after dosing -- CI confidence interval -- CV% coefficient of variation as a percentage -- ITTI intent-to-treat infected -- PA polymerase acidic protein -- PK pharmacokinetics -- RCT randomized controlled trial -- RT-PCR reverse transcription-polymerase chain reaction -- SD standard deviation -- TCID50 50% tissue culture infective dose -- TTIA time to illness alleviation; Chemotherapy -- Periodicals; Infection -- Periodicals; Communicable diseases -- Chemotherapy -- Periodicals; 615.5805
• DOI: 10.1016/j.jiac.2021.05.009
• Languages: English
• ISSNs: 1341-321X

Abstract

Abstract: Introduction: Baloxavir marboxil is an oral anti-influenza drug with demonstrated safety and efficacy in pediatric patients when a 2% granules formulation is administered at 1 mg/kg. This study assessed safety, effectiveness, and pharmacokinetics of a higher dose (2 mg/kg) of baloxavir marboxil 2% granules in pediatric patients weighing &lt;20 kg. Methods: This multicenter, open-label, noncontrolled study was conducted at 15 sites in Japan (January 2019–March 2020; JapicCTI-194577). Patients aged &lt;12 years with confirmed influenza received a single oral dose of baloxavir marboxil at 2 mg/kg if body weight was &lt;10 kg or 20 mg if ≥ 10 to &lt;20 kg. Safety, pharmacokinetics, effectiveness (time to illness alleviation [TTIA] of influenza; time to resolution of fever; virus titer), and polymerase acidic protein (PA) substituted viruses were assessed over 22 days. Results: 45 patients, all aged ≤6 years, were enrolled. Adverse events were reported in 24 (53.3%) patients, most commonly nasopharyngitis, diarrhea, and upper respiratory tract infection. Median (95% confidence interval [CI]) TTIA was 37.8 (27.5–46.7) hours; median (95% CI) time to resolution of fever was 22.0 (20.2–28.6) hours. A &gt;4 log decrease in mean viral titer occurred at day 2 and a subsequent temporary 1–2 log increase in patients with influenza A(H3N2) and B. Treatment-emergent PA/I38X-substituted virus was detected in 16/39 (41.0%) patients, but no prolonged TTIA or time to resolution of fever was associated with its presence. Conclusions: Baloxavir granules administered at 2 mg/kg in children &lt;20 kg were well tolerated, with symptom alleviation similar to 1 mg/kg.