Joji Toyota1, Yoshiyasu Karino2, Fumitaka Suzuki3, Fusao Ikeda4, Akio Ido5, Katsuaki Tanaka6, Koichi Takaguchi7, Atsushi Naganuma8, Eiichi Tomita9, Kazuaki Chayama10, Shigetoshi Fujiyama11, Yukiko Inada12, Hitoshi Yoshiji13, Hideaki Watanabe14, Hiroki Ishikawa14, Wenhua Hu15, Fiona McPhee15, Misti Linaberry16, Philip D Yin15, Eugene Scott Swenson15, Hiromitsu Kumada3. 1. 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. 2. Department of Gastroenterology, Sapporo-Kosei General Hospital, 8-5 Higashi Kita-3-jo Chuo-ku, Sapporo-shi, Hokkaido, Japan. 3. Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, Japan. 4. Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama, Japan. 5. Kagoshima University, 8-35-1 Sakuragoka, Kagoshima-shi, Kagoshima, Japan. 6. Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa, Japan. 7. Kagawa Prefectural Central Hospital, 1-2-1 Asahimachi, Takamatsu-shi, Kagawa, Japan. 8. Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki-shi, Gunma, Japan. 9. Gifu Municipal Hospital, 7-1 Kashima-cho, Gifu-shi, Gifu, Japan. 10. Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima-shi, Hiroshima, Japan. 11. Kumamoto Shinto General Hospital, 1-17-27 Shinyashiki, Chuo-ku, Kumamoto, Kumamoto, Japan. 12. Miyazaki Medical Center Hospital, 2-16 Takamatsu-cho, Miyazaki-shi, Miyazaki, Japan. 13. Nara Medical University, 840 Shijocho, Kashihara-shi, Nara, Japan. 14. Bristol-Myers Squibb K.K., 5-1 Nishi-Shinjuku 6-chome, Shinjuku-ku, Tokyo, Japan. 15. Bristol-Myers Squibb, 5 Research Parkway, Wallingford, CT, USA. 16. Bristol-Myers Squibb, 100 Nassau Park Blvd, Princeton, NJ, USA.
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. CONCLUSION: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.
RCT Entities:
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-infectedpatients 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. CONCLUSION: 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: Fred Poordad; William Sievert; Lindsay Mollison; Michael Bennett; Edmund Tse; Norbert Bräu; James Levin; Thomas Sepe; Samuel S Lee; Peter Angus; Brian Conway; Stanislas Pol; Nathalie Boyer; Jean-Pierre Bronowicki; Ira Jacobson; Andrew J Muir; K Rajender Reddy; Edward Tam; Grisell Ortiz-Lasanta; Victor de Lédinghen; Mark Sulkowski; Navdeep Boparai; Fiona McPhee; Eric Hughes; E Scott Swenson; Philip D Yin Journal: JAMA Date: 2015-05-05 Impact factor: 56.272
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Authors: Fiona McPhee; Amy K Sheaffer; Jacques Friborg; Dennis Hernandez; Paul Falk; Guangzhi Zhai; Steven Levine; Susan Chaniewski; Fei Yu; Diana Barry; Chaoqun Chen; Min S Lee; Kathy Mosure; Li-Qiang Sun; Michael Sinz; Nicholas A Meanwell; Richard J Colonno; Jay Knipe; Paul Scola Journal: Antimicrob Agents Chemother Date: 2012-08-06 Impact factor: 5.191