The Safety and Antiviral Activity of BZF961 with or without Ritonavir in Patients Infected with Hepatitis C Virus: A Randomized, Multicenter Trial.
Clin Ther
; 40(9): 1567-1581.e4, 2018 09.
Article
em En
| MEDLINE
| ID: mdl-30185394
ABSTRACT
PURPOSE:
Infection with hepatitis C virus is the leading cause of infectious disease mortality in the United States. BZF961 is a novel small molecule inhibitor of the hepatitis C virus NS3-4A protease. Here we present the results of a randomized, double-blinded, placebo-controlled, multicentered study in treatment-naïve patients with chronic hepatitis C virus genotype-1 infection.METHODS:
Patients were enrolled sequentially in 2 parts and treated for 3days. BZF961 was administered as monotherapy (500mg BID for 3 days) or in combination with the cytochrome P450 3A4 inhibitor ritonavir to boost its exposure (BZF961 10, 20, or 50mg QD or BID).FINDINGS:
BZF961 was safe and well tolerated in the patients studied with no serious adverse events. There were no appreciable differences in adverse events among patients who received BZF961, BZF961 with ritonavir, or placebo. There was a significant, clinically meaningful reduction in viral load from baseline in patients treated either with BZF961 500mg every 12hours alone or BZF961 50mg every 12hours in combination with ritonavir. Activity against the hepatitis C virus of the lower-dose regimens was apparent but more modest. There were no relevant changes from baseline viral loads in placebo-treated patients. IMPLICATIONS Coadministration of ritonavir with BZF961 boosted BZF961 exposure (including Cmin, which is the clinically relevant parameter associated with antiviral activity) in a therapeutic range with less variability compared with BZF961 alone. For strategic reasons, BZF961 is no longer under development.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
/
4_TD
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6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Compostos Orgânicos
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Ritonavir
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Hepatite C Crônica
Tipo de estudo:
Clinical_trials
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Clin Ther
Ano de publicação:
2018
Tipo de documento:
Article