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Hepatology International

, Volume 3, Issue 3, pp 445–452 | Cite as

Antiviral activity, dose–response relationship, and safety of entecavir following 24-week oral dosing in nucleoside-naive Japanese adult patients with chronic hepatitis B: a randomized, double-blind, phase II clinical trial

  • Michiko ShindoEmail author
  • Kazuaki Chayama
  • Satoshi Mochida
  • Joji Toyota
  • Eiichi Tomita
  • Hiromitsu Kumada
  • Osamu Yokosuka
  • Michio Sata
  • Norio Hayashi
  • Kazuyuki Suzuki
  • Takeshi Okanoue
  • Hirohito Tsubouchi
  • Hiroki Ishikawa
  • Taku Seriu
  • Masao Omata
Original Article

Abstract

Purpose

A randomized, double-blind, multicenter study (ETV-047) was conducted to evaluate the dose–response relationship of entecavir and compare its antiviral activity and safety with lamivudine in Japanese patients with chronic hepatitis B (CHB).

Methods

One hundred thirty-seven nucleoside-naive adult patients with CHB were randomized to once-daily oral doses of entecavir 0.01, 0.1, or 0.5 mg or lamivudine 100 mg for 24 weeks. The primary efficacy end point used to evaluate the dose–response relationship was mean change from baseline in serum hepatitis B virus (HBV) DNA level at week 22, as determined by polymerase chain reaction assay.

Results

Entecavir demonstrated a clear dose–response relationship, with mean change from baseline in serum HBV DNA level of −3.11, −4.77, and −5.16 log10 copies/ml with entecavir 0.01, 0.1, and 0.5 mg, respectively. Entecavir 0.5 mg was superior to lamivudine 100 mg for the mean change in HBV DNA level (−5.16 vs. −4.29 log10 copies/ml; P = 0.007). The overall incidence of adverse events was comparable between treatment groups. Two patients discontinued treatment because of adverse events (one with liver cirrhosis [entecavir 0.5 mg] and one with grade 4 serum alanine aminotransferase (ALT) elevation, nausea, and malaise [lamivudine 100 mg]). Serum ALT flares were observed in four patients; flares were associated with 2 log10 reductions or more in HBV DNA level and resolved without dose interruption.

Conclusion

Entecavir 0.01–0.5 mg is well tolerated and produces a dose-dependent reduction in viral load in nucleoside-naive Japanese patients with CHB. Compared with lamivudine 100 mg, entecavir 0.1 mg demonstrated noninferiority and entecavir 0.5 mg was superior in this population.

Keywords

Chronic hepatitis B Entecavir Lamivudine HBV DNA ALT flare 

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Copyright information

© Asian Pacific Association for the Study of the Liver 2009

Authors and Affiliations

  • Michiko Shindo
    • 1
    Email author
  • Kazuaki Chayama
    • 2
  • Satoshi Mochida
    • 3
  • Joji Toyota
    • 4
  • Eiichi Tomita
    • 5
  • Hiromitsu Kumada
    • 6
  • Osamu Yokosuka
    • 7
  • Michio Sata
    • 8
  • Norio Hayashi
    • 9
  • Kazuyuki Suzuki
    • 10
  • Takeshi Okanoue
    • 11
  • Hirohito Tsubouchi
    • 12
  • Hiroki Ishikawa
    • 13
  • Taku Seriu
    • 13
  • Masao Omata
    • 14
  1. 1.Division of Liver Disease, Department of Internal MedicineAkashi Municipal HospitalHyogoJapan
  2. 2.Department of Medicine and Molecular Science, Graduate School of Biomedical SciencesHiroshima UniversityHiroshimaJapan
  3. 3.Department of Gastroenterology and HepatologySaitama Medical UniversitySaitamaJapan
  4. 4.Department of HepatologySapporo Kosei General HospitalHokkaidoJapan
  5. 5.Department of GastroenterologyGifu Municipal HospitalGifuJapan
  6. 6.Department of HepatologyToranomon HospitalTokyoJapan
  7. 7.Department of Medicine and Clinical Oncology, Graduate School of MedicineChiba UniversityChibaJapan
  8. 8.Department of GastroenterologyKurume University School of MedicineFukuokaJapan
  9. 9.Department of Gastroenterology and HepatologyOsaka University Graduate School of MedicineOsakaJapan
  10. 10.Department of Internal MedicineIwate Medical UniversityIwateJapan
  11. 11.Department of GastroenterologySaiseikai Suita HospitalOsakaJapan
  12. 12.Department of Digestive Disease and Lifestyle-Related DiseaseKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
  13. 13.Pharmaceutical Research InstituteBristol-Myers Squibb JapanTokyoJapan
  14. 14.Department of Gastroenterology, Graduate School of MedicineUniversity of TokyoTokyoJapan

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