title: Daclatasvir/asunaprevir/beclabuvir fixed-dose combination in Japanese patients with HCV genotype 1 infection.
abstract: BACKGROUND
  DCV-TRIO, a fixed-dose combination of daclatasvir (pangenotypic NS5A inhibitor), asunaprevir (NS3/4A protease inhibitor), and beclabuvir (non-nucleoside NS5B inhibitor), has achieved high rates of sustained virologic response at post-treatment Week 12 (SVR12) in phase 3 studies.
  
  
  METHODS
  In this phase 3 study, DCV-TRIO for 12 weeks and daclatasvir plus asunaprevir (DUAL) for 24 weeks were studied in Japanese patients infected with HCV genotype 1 (99 % genotype 1b).
  
  
  RESULTS
  SVR12 rates ≥95 % were achieved in both treatment-naive (N = 152) and interferon-experienced (N = 65) cohorts treated with DCV-TRIO for 12 weeks and were comparable across patient subgroups, including patients aged ≥65 years and those with cirrhosis. DUAL recipients (N = 75) had an SVR12 rate of 87 %. In the absence of baseline resistance-associated polymorphisms at positions NS5A-Y93H or -L31, SVR12 rates were 98 % with DCV-TRIO or DUAL. Among genotype 1b-infected patients with baseline Y93H or L31 polymorphisms, 35/38 (92 %) DCV-TRIO recipients, and 7/16 (44 %) DUAL recipients achieved SVR12. Adverse events, mostly liver related, led to treatment discontinuation in 10 % of DCV-TRIO recipients. In this group, SVR12 was achieved by 3/9 patients who discontinued before Week 4 and by 12/12 patients who completed ≥4 weeks of DCV-TRIO. Treatment-related serious adverse events occurred in 4 and 3 % of DCV-TRIO and DUAL recipients, respectively. Seven patients (9 %) discontinued DUAL due to adverse events. No deaths occurred.
  
  
  CONCLUSIONS
  SVR12 was achieved by 96 % of Japanese patients with HCV genotype 1 infection after 12 weeks of treatment with the DCV-TRIO regimen. DCV-TRIO and DUAL exhibited comparable safety profiles.
authors: Department of Gastroenterology, Sapporo-Kosei General Hospital, 8-5 Higashi Kita-3-jo Chuo-ku, Sapporo-shi, Hokkaido, Japan. joji.toyota@ja-hokkaidoukouseiren.or.jp.
authors: Joji
authors: J
authors: Toyota
authors: Department of Gastroenterology, Sapporo-Kosei General Hospital, 8-5 Higashi Kita-3-jo Chuo-ku, Sapporo-shi, Hokkaido, Japan.
authors: Yoshiyasu
authors: Y
authors: Karino
authors: Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, Japan.
authors: Fumitaka
authors: F
authors: Suzuki
authors: Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama, Japan.
authors: Fusao
authors: F
authors: Ikeda
authors: Kagoshima University, 8-35-1 Sakuragoka, Kagoshima-shi, Kagoshima, Japan.
authors: Akio
authors: A
authors: Ido
authors: Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa, Japan.
authors: Katsuaki
authors: K
authors: Tanaka
authors: Kagawa Prefectural Central Hospital, 1-2-1 Asahimachi, Takamatsu-shi, Kagawa, Japan.
authors: Koichi
authors: K
authors: Takaguchi
authors: Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki-shi, Gunma, Japan.
authors: Atsushi
authors: A
authors: Naganuma
authors: Gifu Municipal Hospital, 7-1 Kashima-cho, Gifu-shi, Gifu, Japan.
authors: Eiichi
authors: E
authors: Tomita
authors: Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima-shi, Hiroshima, Japan.
authors: Kazuaki
authors: K
authors: Chayama
authors: Kumamoto Shinto General Hospital, 1-17-27 Shinyashiki, Chuo-ku, Kumamoto, Kumamoto, Japan.
authors: Shigetoshi
authors: S
authors: Fujiyama
authors: Miyazaki Medical Center Hospital, 2-16 Takamatsu-cho, Miyazaki-shi, Miyazaki, Japan.
authors: Yukiko
authors: Y
authors: Inada
authors: Nara Medical University, 840 Shijocho, Kashihara-shi, Nara, Japan.
authors: Hitoshi
authors: H
authors: Yoshiji
authors: Bristol-Myers Squibb K.K., 5-1 Nishi-Shinjuku 6-chome, Shinjuku-ku, Tokyo, Japan.
authors: Hideaki
authors: H
authors: Watanabe
authors: Bristol-Myers Squibb K.K., 5-1 Nishi-Shinjuku 6-chome, Shinjuku-ku, Tokyo, Japan.
authors: Hiroki
authors: H
authors: Ishikawa
authors: Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT, USA.
authors: Wenhua
authors: W
authors: Hu
authors: Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT, USA.
authors: Fiona
authors: F
authors: McPhee
authors: Bristol-Myers Squibb, 100 Nassau Park Blvd, Princeton, NJ, USA.
authors: Misti
authors: M
authors: Linaberry
authors: Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT, USA.
authors: Philip D
authors: PD
authors: Yin
authors: Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT, USA.
authors: Eugene Scott
authors: ES
authors: Swenson
authors: Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, Japan.
authors: Hiromitsu
authors: H
authors: Kumada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001552:Benzazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002219:Carbamates; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007546:Isoquinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000821:virology; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D012367:RNA, Viral / Q000097:blood; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives
chemical_list: C587012:8-cyclohexyl-N-((dimethylamino)sulfonyl)-1,1a,2,12b-tetrahydro-11-methoxy-1a-((3-methyl-3,8-diazabicyclo(3.2.1)oct-8-yl)carbonyl)cycloprop(d)indolo(2,1-a)(2)benzazepine-5-carboxamide; D000998:Antiviral Agents; D001552:Benzazepines; D002219:Carbamates; D004338:Drug Combinations; D007093:Imidazoles; D007211:Indoles; D007546:Isoquinolines; D011759:Pyrrolidines; D012367:RNA, Viral; D013449:Sulfonamides; D014633:Valine; C549273:daclatasvir; C571889:asunaprevir
keywords: Direct-acting antiviral; HCV therapy; NS3/4A inhibitor; NS5A inhibitor; NS5B inhibitor