Itx 5061 Quantitation in Human Plasma with Reverse Phase Liquid Chromatography and Mass Spectrometry Detection

Hochreiter, Jill; Lapham, Jill; Wong‐Staal, Flossie; McKelvy, Jeffrey F.; Sulkowski, Mark S.; Glesby, Marshall J.; Johnson, Victoria A.; Morse, Gene D.

doi:10.3851/imp2354

Cited by 2 publications

(1 citation statement)

References 10 publications

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“…Plasma ITX5061 concentrations were measured by liquid chromatography/mass spectrometry . Because ITX5061 is primarily metabolized in the liver, an interim analysis of ITX5061 plasma concentrations was performed on the first 3 treated patients.…”

Section: Methodsmentioning

confidence: 99%

Effect of scavenger receptor class B type I antagonist ITX5061 in patients with hepatitis C virus infection undergoing liver transplantation

et al. 2016

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Hepatitis C virus (HCV) entry inhibitors have been hypothesized to prevent infection of the liver after transplantation. ITX5061 is a Scavenger Receptor B-I (SR-BI) antagonist that blocks HCV entry and infection in vitro. We assessed the safety and efficacy of ITX5061 to limit HCV infection of the graft. The study included 23 HCV infected patients undergoing liver transplantation. The first 13 “control” patients did not receive drug. The subsequent 10 patients received ITX5061 150 mg immediately pre- and post-transplant, and daily for 1 week thereafter. ITX5061 pharmacokinetics and plasma HCV RNA were quantified. Viral genetic diversity was measured by ultradeep pyrosequencing. ITX5061 was well tolerated with measurable plasma concentrations during therapy. Whilst the median HCV RNA reduction was greater in ITX treated patients at all time points in the first week after transplantation there was no difference in the overall change in the area over the HCV RNA curve in the 7-day treatment period. However, in genotype 1 infected patients treatment was associated with a sustained reduction in HCV RNA levels compared to the control group (area over the HCV RNA curve analysis, p=0.004). Ultradeep pyrosequencing revealed a complex and evolving pattern of HCV variants infecting the graft during the first week. ITX5061 significantly limited viral evolution where the median divergence between day 0 and day 7 was 3.5% in the control group compared to 0.1% in the treated group. Conclusions ITX5061 reduces plasma HCV RNA post transplant notably in genotype 1 infected patients and slows viral evolution. Following liver transplantation the likely contribution of extrahepatic reservoirs of HCV necessitates combining entry inhibitors such as ITX5061 with inhibitors of replication in future studies.

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Section: Methodsmentioning

confidence: 99%

Effect of scavenger receptor class B type I antagonist ITX5061 in patients with hepatitis C virus infection undergoing liver transplantation

et al. 2016

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Safety and Antiviral Activity of the HCV Entry Inhibitor ITX5061 in Treatment-Naive HCV-Infected Adults: A Randomized, Double-Blind, Phase 1b Study

Sulkowski

Kang

Matining

et al. 2013

The Journal of Infectious Diseases

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Itx 5061 Quantitation in Human Plasma with Reverse Phase Liquid Chromatography and Mass Spectrometry Detection

Abstract: The ITX 5061 assay is accurate and reproducible with a wide linear range and will be used for pharmacokinetic analysis and dose-finding studies in HCV-monoinfected patients.

Cited by 2 publications

References 10 publications

Effect of scavenger receptor class B type I antagonist ITX5061 in patients with hepatitis C virus infection undergoing liver transplantation

Effect of scavenger receptor class B type I antagonist ITX5061 in patients with hepatitis C virus infection undergoing liver transplantation

Safety and Antiviral Activity of the HCV Entry Inhibitor ITX5061 in Treatment-Naive HCV-Infected Adults: A Randomized, Double-Blind, Phase 1b Study

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