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Baloxavir marboxil in Japanese patients with seasonal influenza: Dose response and virus type/subtype outcomes from a randomized phase 2 study.
Antiviral Res. 2019 03; 163:75-81.AR

Abstract

BACKGROUND

Baloxavir marboxil (baloxavir) is an antiviral drug that inhibits the viral "cap-snatching" step in virus RNA transcription initiation. In Phase 2 study, baloxavir significantly shortend the time to alleviation of symptoms (TTAS) and showed significantly greater reduction in influenza virus titer compared with placebo. This provides additional outcomes including efficacy against virus types/subtypes and pharmacokinetic/pharmacodynamic (PK/PD) analysis.

METHODS

Subgroup analyses by virus types/subtype were conducted for the primary and key secondary endpoints. Blood samples were collected totally at 2 to 5 points including Day 2 after baloxavir dosing. PK/PD analyses were conducted for TTAS and change in virus titer using the liner model and the Emax model, respectively.

RESULTS

The median TTAS in each baloxavir dose group was significantly shorter than in the placebo group for patients with A/H1N1pdm virus, and was numerically shorter than the placebo group for patients with A/H3N2 and type B virus. Baloxavir significantly reduced virus titer within 1 day after treatment: for A/H1N1pdm, A/H3N2, and B virus, all 3 doses of baloxavir marboxil reduced virus titer on Day 2 to a greater extent than placebo. No clear PK/PD relationships were found for the TTAS, but the larger reduction in virus titer was observed in increasing C24.

CONCLUSION

These results support that baloxavir marboxil will be effective against a range of virus types/subtypes.

Authors+Show Affiliations

Research Division for Development of Anti-Infective Agents, Faculty of Medical Science and Welfare, Tohoku Bunka Gakuen University, Sendai, Japan. Electronic address: akiwa@office.tbgu.ac.jp.Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan.Hirotsu Medical Clinic, Kawasaki, Japan.Shionogi & Co., Ltd., Osaka, Japan.Shionogi & Co., Ltd., Osaka, Japan.Shionogi & Co., Ltd., Osaka, Japan.Shionogi & Co., Ltd., Osaka, Japan.Shionogi Inc., Florham Park, NJ, USA.Shionogi & Co., Ltd., Osaka, Japan.Shionogi & Co., Ltd., Osaka, Japan.

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30684563

Citation

Watanabe, Akira, et al. "Baloxavir Marboxil in Japanese Patients With Seasonal Influenza: Dose Response and Virus Type/subtype Outcomes From a Randomized Phase 2 Study." Antiviral Research, vol. 163, 2019, pp. 75-81.
Watanabe A, Ishida T, Hirotsu N, et al. Baloxavir marboxil in Japanese patients with seasonal influenza: Dose response and virus type/subtype outcomes from a randomized phase 2 study. Antiviral Res. 2019;163:75-81.
Watanabe, A., Ishida, T., Hirotsu, N., Kawaguchi, K., Ishibashi, T., Shishido, T., Sato, C., Portsmouth, S., Tsuchiya, K., & Uehara, T. (2019). Baloxavir marboxil in Japanese patients with seasonal influenza: Dose response and virus type/subtype outcomes from a randomized phase 2 study. Antiviral Research, 163, 75-81. https://doi.org/10.1016/j.antiviral.2019.01.012
Watanabe A, et al. Baloxavir Marboxil in Japanese Patients With Seasonal Influenza: Dose Response and Virus Type/subtype Outcomes From a Randomized Phase 2 Study. Antiviral Res. 2019;163:75-81. PubMed PMID: 30684563.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Baloxavir marboxil in Japanese patients with seasonal influenza: Dose response and virus type/subtype outcomes from a randomized phase 2 study. AU - Watanabe,Akira, AU - Ishida,Tadashi, AU - Hirotsu,Nobuo, AU - Kawaguchi,Keiko, AU - Ishibashi,Toru, AU - Shishido,Takao, AU - Sato,Chisako, AU - Portsmouth,Simon, AU - Tsuchiya,Kenji, AU - Uehara,Takeki, Y1 - 2019/01/23/ PY - 2018/09/11/received PY - 2019/01/21/revised PY - 2019/01/22/accepted PY - 2019/1/27/pubmed PY - 2020/3/14/medline PY - 2019/1/27/entrez KW - Antiviral KW - Baloxavir marboxil KW - Influenza KW - Japan SP - 75 EP - 81 JF - Antiviral research JO - Antiviral Res VL - 163 N2 - BACKGROUND: Baloxavir marboxil (baloxavir) is an antiviral drug that inhibits the viral "cap-snatching" step in virus RNA transcription initiation. In Phase 2 study, baloxavir significantly shortend the time to alleviation of symptoms (TTAS) and showed significantly greater reduction in influenza virus titer compared with placebo. This provides additional outcomes including efficacy against virus types/subtypes and pharmacokinetic/pharmacodynamic (PK/PD) analysis. METHODS: Subgroup analyses by virus types/subtype were conducted for the primary and key secondary endpoints. Blood samples were collected totally at 2 to 5 points including Day 2 after baloxavir dosing. PK/PD analyses were conducted for TTAS and change in virus titer using the liner model and the Emax model, respectively. RESULTS: The median TTAS in each baloxavir dose group was significantly shorter than in the placebo group for patients with A/H1N1pdm virus, and was numerically shorter than the placebo group for patients with A/H3N2 and type B virus. Baloxavir significantly reduced virus titer within 1 day after treatment: for A/H1N1pdm, A/H3N2, and B virus, all 3 doses of baloxavir marboxil reduced virus titer on Day 2 to a greater extent than placebo. No clear PK/PD relationships were found for the TTAS, but the larger reduction in virus titer was observed in increasing C24. CONCLUSION: These results support that baloxavir marboxil will be effective against a range of virus types/subtypes. SN - 1872-9096 UR - https://www.unboundmedicine.com/medline/citation/30684563/Baloxavir_marboxil_in_Japanese_patients_with_seasonal_influenza:_Dose_response_and_virus_type/subtype_outcomes_from_a_randomized_phase_2_study_ DB - PRIME DP - Unbound Medicine ER -