2012
DOI: 10.1016/s0168-8278(12)61200-8
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1188 Gs-6620, a Liver-Targeted Nucleotide Prodrug, Exhibits Antiviral Activity and Favorable Safety Profile Over 5 Days in Treatment Naive Chronic HCV Genotype 1 Subjects

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Cited by 9 publications
(13 citation statements)
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“…The safety, tolerability, pharmacokinetics, and anti-HCV activity of GS-6620 were assessed in genotype 1 treatment-naive subjects over 5 days in a first-in-human clinical study (5). GS-6620 demonstrated the potential for potent anti-HCV activity, but substantial intra-and intersubject pharmacokinetic and pharmacodynamic variability were observed.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…The safety, tolerability, pharmacokinetics, and anti-HCV activity of GS-6620 were assessed in genotype 1 treatment-naive subjects over 5 days in a first-in-human clinical study (5). GS-6620 demonstrated the potential for potent anti-HCV activity, but substantial intra-and intersubject pharmacokinetic and pharmacodynamic variability were observed.…”
Section: Discussionmentioning
confidence: 99%
“…The studies we conducted to characterize the metabolic profile of GS-6620 include those regarding: (i) metabolism in primary hepatocytes isolated from hamsters, dogs, monkeys, and humans, (ii) the molecular mechanism of intracellular activation, (iii) stability in plasma and intestinal and hepatic subcellular fractions, (iv) blood plasma and liver pharmacokinetics in golden Syrian hamsters, beagle dogs, and cynomolgus monkeys, and (v) the characterization of factors affecting intestinal absorption. These nonclinical results are used to help interpret findings from the recently reported first-in-human study of GS-6620 in treatment-naive subjects chronically infected with HCV genotype 1 (5).…”
mentioning
confidence: 99%
“…Thus, it was hoped that potent antiviral activity would be observed for GS-6620 in clinical studies. The safety, tolerability, pharmacokinetics, and anti-HCV activity of GS-6620 were assessed in genotype 1 treatment-naive subjects over 5 days in a first-in-human clinical study (37). While demonstrating the potential for potent antiviral activity (viral load reductions Ͼ4 logs in a few patients), high doses of up to 900 mg twice daily (BID) were required for efficacy, and substantial intra-and intersubject pharmacokinetic and pharmacodynamic variability was observed.…”
Section: Discussionmentioning
confidence: 99%
“…This mutation conferred >200-fold resistance in in vitro experiments with purified recombination S282T mutant enzyme (Fenaux et al, 2011). Oral administration of GS-6620 to animals resulted in efficient delivery of the nucleoside triphosphate metabolite into the liver (Lawitz et al, 2012b). …”
Section: Gs-6620mentioning
confidence: 99%
“…Gilead Sciences indicated that without further optimization of drug delivery to improve PK and antiviral activity, future clinical development would not occur for GS-6620 (Lawitz et al, 2012b). …”
Section: Gs-6620mentioning
confidence: 99%