Evaluation of VCH-759 monotherapy in hepatitis C infection
| Autor: | Olivier Nicolas, Samuel S. Lee, Maribel Rodriguez-Torres, Curtis Cooper, Eric Lawitz, Jean Bedard, Frank H. Anderson, Peter Ghali, Nathalie Chauret, L. Proulx, Isabel Boivin, Roch Thibert |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male medicine.medical_specialty Hepatitis C virus Hepacivirus Carboxylic Acids Cmax Thiophenes Viral Nonstructural Proteins medicine.disease_cause Placebo Antiviral Agents Gastroenterology Double-Blind Method Internal medicine medicine Humans Dosing Hepatology biology business.industry Area under the curve Hepatitis C Middle Aged biology.organism_classification medicine.disease Phenotype Tolerability Immunology Female business |
| Zdroj: | Journal of Hepatology. 51:39-46 |
| ISSN: | 0168-8278 |
| DOI: | 10.1016/j.jhep.2009.03.015 |
| Popis: | Background/Aims VCH-759 is a non-nucleoside inhibitor of HCV RNA-dependent polymerase with sub-micromolar IC 50 values versus genotype 1a/1b replicons. Methods The antiviral activity, pharmacokinetics and tolerability of VCH-759 administered as monotherapy for 10 days with a 14 day follow-up period were evaluated in 31 treatment-nai¨ve genotype 1 participants. Three cohorts received: 400mg thrice (t.i.d.), 800mg twice (b.i.d.), 800mg t.i.d or placebo. Results VCH-759 was well tolerated with the most frequent adverse event being gastrointestinal upset in both the active and placebo groups attributable, in part, to the dosing vehicle. VCH-759 was rapidly absorbed and trough plasma levels were at or above the IC 90 (non protein-adjusted) for all dosing regimens. The mean maximal decrease in HCV RNA log 10 (IU/mL) was 1.97, 2.30 and 2.46 for 400mg t.i.d., 800mg b.i.d. and 800mg t.i.d. doses. Viral polymerase genotypic sequencing revealed emergence of HCV variants in a majority of participants that coincided with on-treatment viral rebound. Conclusions VCH-759 was well tolerated and achieved a⩾2 log 10 decline in HCV RNA with 800mg b.i.d. and t.i.d doses. In a subset of participants, viral rebound was observed and associated with resistant variants. This data supports further evaluation of VCH-759 in combination with interferon–ribavirin treatment. |
| Databáze: | OpenAIRE |
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