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Ann Hepatol ; 15(3): 333-49, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27049487

RESUMEN

INTRODUCTION & AIM: Faldaprevir is a potent once-daily (q.d.) hepatitis C virus (HCV) NS3/4A protease inhibitor. The STARTVerso1 and STARTVerso2 phase 3 studies evaluated faldaprevir plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in treatment-naïve patients with chronic HCV genotype-1 infection. MATERIAL AND METHODS: Patients were randomized 1:2:2 to receive placebo, faldaprevir 120 mg q.d. (12 or 24 weeks) or faldaprevir 240 mg q.d. (12 weeks) all with PegIFN/RBV (24-48 weeks). Faldaprevir 120 mg for 12 weeks only (STARTVerso1 only) required early treatment success (ETS, HCV RNA < 25 IU/mL at week 4 and undetected at week 8). All faldaprevir-treated patients with ETS stopped PegIFN/RBV at week 24. Primary endpoint: sustained virologic response 12 weeks post-treatment (SVR12). RESULTS: SVR12 rates were significantly higher for patients treated with faldaprevir 120 or 240 mg (72% and 73%, respectively) compared with placebo (50%); estimated differences (adjusted for trial, race, and genotype-1 subtype) faldaprevir 120 mg 24% (95% CI: 17-31%, P < 0.0001), faldaprevir 240 mg 23% (95% CI: 16-30%, P < 0.0001). Subgroup analyses consistently showed higher SVR12 rates for patients receiving faldaprevir compared with placebo. The incidence of adverse events (AEs) was similar in faldaprevir 120-mg and placebo groups and slightly higher in the faldaprevir 240-mg group. Serious Aes were reported in 6%, 7%, and 8% of patients in placebo, faldaprevir 120-mg, and faldaprevir 240-mg groups, respectively. CONCLUSION: Addition of faldaprevir to PegIFN/RBV increased SVR12 in patients with HCV genotype-1, and was well tolerated. Faldaprevir 120 mg is effective in the treatment of HCV genotype-1. ClinicalTrials.gov: NCT01343888 and NCT01297270.


Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepatitis C/tratamiento farmacológico , Oligopéptidos/uso terapéutico , Inhibidores de Proteasas/uso terapéutico , Ribavirina/uso terapéutico , Tiazoles/uso terapéutico , Adulto , Ácidos Aminoisobutíricos , Antivirales/efectos adversos , Biomarcadores/sangre , Proteínas Portadoras/antagonistas & inhibidores , Proteínas Portadoras/metabolismo , Ensayos Clínicos Fase III como Asunto , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/enzimología , Hepacivirus/genética , Hepatitis C/sangre , Hepatitis C/diagnóstico , Humanos , Interferón-alfa/efectos adversos , Interferón-alfa/uso terapéutico , Péptidos y Proteínas de Señalización Intracelular , Leucina/análogos & derivados , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Oligopéptidos/efectos adversos , Polietilenglicoles/efectos adversos , Polietilenglicoles/uso terapéutico , Prolina/análogos & derivados , Inhibidores de Proteasas/efectos adversos , Quinolinas , ARN Viral/sangre , Ensayos Clínicos Controlados Aleatorios como Asunto , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Ribavirina/efectos adversos , Tiazoles/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Carga Viral , Proteínas no Estructurales Virales/antagonistas & inhibidores , Proteínas no Estructurales Virales/metabolismo
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