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Daclatasvir combined with peginterferon alfa-2a and ribavirin in Japanese patients infected with hepatitis C genotype 1.
Antivir Ther. 2014; 19(5):501-10.AT

Abstract

BACKGROUND

New direct-acting antiviral agents are currently being developed to treat chronic HCV. The efficacy and safety of daclatasvir combined with peginterferon alfa-2a (alfa-2a) and ribavirin were assessed in a randomized, double-blind Phase IIa study of Japanese patients with chronic HCV genotype-1 infection.

METHODS

Japanese patients who were treatment-naive (n=25) or prior null (n=12) or partial (n=5) responders received once-daily daclatasvir 10 mg or 60 mg or placebo in combination with alfa-2a and ribavirin. Daclatasvir recipients with a protocol-defined response (HCV RNA<15 IU/ml at week 4 and undetectable at week 12) were treated for 24 weeks; placebo recipients and patients without a protocol-defined response were treated for 48 weeks.

RESULTS

Sustained virological response at 24 weeks post-treatment (SVR24) was achieved by 89% and 100% of treatment-naive patients receiving daclatasvir 10 mg and 60 mg, respectively, versus 75% in placebo recipients. Virological failure was more frequent in prior non-responder patients, with 50% and 78% achieving SVR24 in daclatasvir 10 mg and 60 mg groups, respectively. Adverse events occurred with similar frequency among treatment groups and were consistent with the adverse event profile of alfa-2a/ribavirin alone. The most commonly reported adverse events included pyrexia, alopecia, anaemia, lymphopenia, neutropenia, pruritus and diarrhoea. Three patients discontinued treatment due to anaemia.

CONCLUSIONS

Daclatasvir combined with alfa-2a/ribavirin in treatment-naive patients showed greater efficacy than alfa-2a/ribavirin alone and was generally well tolerated. The 60-mg dose of daclatasvir achieved the highest rates of SVR24 in both treatment-naive and non-responder populations and will be evaluated in a Phase III clinical trial.

Authors+Show Affiliations

Musashino Red Cross Hospital, Tokyo, Japan. nizumi@musashino.jrc.or.jp.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

24451151

Citation

Izumi, Namiki, et al. "Daclatasvir Combined With Peginterferon Alfa-2a and Ribavirin in Japanese Patients Infected With Hepatitis C Genotype 1." Antiviral Therapy, vol. 19, no. 5, 2014, pp. 501-10.
Izumi N, Yokosuka O, Kawada N, et al. Daclatasvir combined with peginterferon alfa-2a and ribavirin in Japanese patients infected with hepatitis C genotype 1. Antivir Ther (Lond). 2014;19(5):501-10.
Izumi, N., Yokosuka, O., Kawada, N., Osaki, Y., Yamamoto, K., Sata, M., Ishikawa, H., Ueki, T., Hu, W., McPhee, F., Hughes, E. A., & Kumada, H. (2014). Daclatasvir combined with peginterferon alfa-2a and ribavirin in Japanese patients infected with hepatitis C genotype 1. Antiviral Therapy, 19(5), 501-10. https://doi.org/10.3851/IMP2731
Izumi N, et al. Daclatasvir Combined With Peginterferon Alfa-2a and Ribavirin in Japanese Patients Infected With Hepatitis C Genotype 1. Antivir Ther (Lond). 2014;19(5):501-10. PubMed PMID: 24451151.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Daclatasvir combined with peginterferon alfa-2a and ribavirin in Japanese patients infected with hepatitis C genotype 1. AU - Izumi,Namiki, AU - Yokosuka,Osamu, AU - Kawada,Norifumi, AU - Osaki,Yukio, AU - Yamamoto,Kazuhide, AU - Sata,Michio, AU - Ishikawa,Hiroki, AU - Ueki,Tomoko, AU - Hu,Wenhua, AU - McPhee,Fiona, AU - Hughes,Eric A, AU - Kumada,Hiromitsu, Y1 - 2014/01/22/ PY - 2013/12/16/accepted PY - 2014/1/24/entrez PY - 2014/1/24/pubmed PY - 2015/7/15/medline SP - 501 EP - 10 JF - Antiviral therapy JO - Antivir. Ther. (Lond.) VL - 19 IS - 5 N2 - BACKGROUND: New direct-acting antiviral agents are currently being developed to treat chronic HCV. The efficacy and safety of daclatasvir combined with peginterferon alfa-2a (alfa-2a) and ribavirin were assessed in a randomized, double-blind Phase IIa study of Japanese patients with chronic HCV genotype-1 infection. METHODS: Japanese patients who were treatment-naive (n=25) or prior null (n=12) or partial (n=5) responders received once-daily daclatasvir 10 mg or 60 mg or placebo in combination with alfa-2a and ribavirin. Daclatasvir recipients with a protocol-defined response (HCV RNA<15 IU/ml at week 4 and undetectable at week 12) were treated for 24 weeks; placebo recipients and patients without a protocol-defined response were treated for 48 weeks. RESULTS: Sustained virological response at 24 weeks post-treatment (SVR24) was achieved by 89% and 100% of treatment-naive patients receiving daclatasvir 10 mg and 60 mg, respectively, versus 75% in placebo recipients. Virological failure was more frequent in prior non-responder patients, with 50% and 78% achieving SVR24 in daclatasvir 10 mg and 60 mg groups, respectively. Adverse events occurred with similar frequency among treatment groups and were consistent with the adverse event profile of alfa-2a/ribavirin alone. The most commonly reported adverse events included pyrexia, alopecia, anaemia, lymphopenia, neutropenia, pruritus and diarrhoea. Three patients discontinued treatment due to anaemia. CONCLUSIONS: Daclatasvir combined with alfa-2a/ribavirin in treatment-naive patients showed greater efficacy than alfa-2a/ribavirin alone and was generally well tolerated. The 60-mg dose of daclatasvir achieved the highest rates of SVR24 in both treatment-naive and non-responder populations and will be evaluated in a Phase III clinical trial. SN - 2040-2058 UR - https://www.unboundmedicine.com/medline/citation/24451151/Daclatasvir_combined_with_peginterferon_alfa_2a_and_ribavirin_in_Japanese_patients_infected_with_hepatitis_C_genotype_1_ L2 - http://www.diseaseinfosearch.org/result/3332 DB - PRIME DP - Unbound Medicine ER -