A randomized, double blind, dose escalation, first time in human study to assess the safety, tolerability, pharmacokinetics, and antiviral activity of single doses of GSK2485852 in chronically infected hepatitis C subjects.
Clin Pharmacol Drug Dev
; 3(6): 439-48, 2014 11.
Article
in En
| MEDLINE
| ID: mdl-27129119
ABSTRACT
This first-time-in-human, randomized, double-blind, placebo-controlled, dose-escalation study assessed the safety, tolerability, pharmacokinetics, and antiviral activity of GSK2485852, a hepatitis C virus (HCV) NS5B inhibitor, in 27 chronically infected HCV genotype-1 subjects. Subjects received GSK2485852 70, 420, and 70 mg with a moderate fat/caloric meal. Safety, pharmacokinetics, antiviral activity, HCV genotype/phenotype, and interleukin 28B genotype were evaluated. A statistically significant reduction in HCV ribonucleic acid (RNA) was observed after a single dose of 420 mg GSK2485852 (-1.33 log10 IU/mL) compared with placebo (-0.09 log10 IU/mL) at 24 hours post-dose. Subjects receiving 70 mg GSK2485852 were exposed to concentrations above the protein-adjusted 90% effective concentration for a short time; none experienced a significant decline in HCV RNA (-0.47 log10 copies/mL). GSK2485852 was readily absorbed; however, the observed geometric mean maximum plasma concentration (Cmax ) and area under the curve (AUC) values were significantly lower than expected due to a higher-than-predicted-oral clearance. Co-administration with food reduced the AUC and Cmax of GSK2485852 by 40% and 70%, respectively. Two metabolites were detected in human blood with one having approximately 50% higher concentrations than those of the parent. GSK2485852 was well-tolerated and exhibited antiviral activity after a single 420 mg dose in HCV subjects.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antiviral Agents
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Protease Inhibitors
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Sulfonamides
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Boronic Acids
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Viral Nonstructural Proteins
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Hepacivirus
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Hepatitis C, Chronic
Type of study:
Clinical_trials
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Diagnostic_studies
/
Prognostic_studies
Limits:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Country/Region as subject:
America do norte
Language:
En
Journal:
Clin Pharmacol Drug Dev
Year:
2014
Document type:
Article
Affiliation country: