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.

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: Joji Toyota, Yoshiyasu Karino, Fumitaka Suzuki, Fusao Ikeda, Akio Ido, Katsuaki Tanaka, Koichi Takaguchi, Atsushi Naganuma, Eiichi Tomita, Kazuaki Chayama, Shigetoshi Fujiyama, Yukiko Inada, Hitoshi Yoshiji, Hideaki Watanabe, Hiroki Ishikawa, Wenhua Hu, Fiona McPhee, Misti Linaberry, Philip D Yin, Eugene Scott Swenson, Hiromitsu Kumada
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 52 Issue 3 Pg. 385-395 (Mar 2017) ISSN: 1435-5922 [Electronic] Japan
• PMID: 27502287 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• 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
• Antiviral Agents
• Benzazepines
• Carbamates
• Drug Combinations
• Imidazoles
• Indoles
• Isoquinolines
• Pyrrolidines
• RNA, Viral
• Sulfonamides
• Valine
• daclatasvir
• asunaprevir

Topics

• Adult
• Aged
• Aged, 80 and over
• Antiviral Agents (administration & dosage, adverse effects, therapeutic use)
• Benzazepines (administration & dosage, adverse effects, therapeutic use)
• Carbamates
• Double-Blind Method
• Drug Administration Schedule
• Drug Combinations
• Female
• Genotype
• Hepacivirus (genetics, isolation & purification)
• Hepatitis C, Chronic (complications, drug therapy, virology)
• Humans
• Imidazoles (administration & dosage, adverse effects, therapeutic use)
• Indoles (administration & dosage, adverse effects, therapeutic use)
• Isoquinolines (administration & dosage, adverse effects, therapeutic use)
• Liver Cirrhosis (virology)
• Male
• Middle Aged
• Pyrrolidines
• RNA, Viral (blood)
• Sulfonamides (administration & dosage, adverse effects, therapeutic use)
• Sustained Virologic Response
• Treatment Outcome
• Valine (analogs & derivatives)