First-in-human study of the pharmacokinetics and antiviral activity of IDX375, a novel nonnucleoside hepatitis C virus polymerase inhibitor

J. De Bruijne; J. Van De Wetering De Rooij; A. A. Van Vliet; X. J. Zhou; M. F. Temam; J. Molles; J. Chen; K. Pietropaolo; J. Z. Sullivan-Bólyai; Mayers; H. W. Reesink

doi:10.1128/AAC.00451-12

First-in-human study of the pharmacokinetics and antiviral activity of IDX375, a novel nonnucleoside hepatitis C virus polymerase inhibitor

J. De Bruijne, J. Van De Wetering De Rooij, A. A. Van Vliet, X. J. Zhou, M. F. Temam, J. Molles, J. Chen, K. Pietropaolo, J. Z. Sullivan-Bólyai, Mayers, H. W. Reesink^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

IDX375 is a potent and selective palm-binding nonnucleoside inhibitor of the hepatitis C virus (HCV) genotype 1 polymerase. This first-in-human study evaluated the safety, tolerability, and pharmacokinetics of IDX375 in healthy volunteers, as well as its antiviral activity in HCV-infected patients. IDX375, as a choline salt, was administered for 1 day to 40 healthy male volunteers (25- to 200-mg IDX375-equivalent single ascending doses and a 200-mg twice-daily [BID] dose) and three patients chronically infected with HCV genotype 1 (200 mg BID only). IDX375 was well absorbed and well tolerated by all of the study participants. A single-day 200-mg BID dose resulted in exposure-related anti-HCV activity with maximal 0.5 to 1.1 log₁₀ reductions in plasma HCV RNA. These observations support further clinical investigations of IDX375.

Original language	English
Pages (from-to)	4525-4528
Number of pages	4
Journal	Antimicrobial Agents and Chemotherapy
Volume	56
Issue number	8
DOIs	https://doi.org/10.1128/AAC.00451-12
Publication status	Published - Aug 2012
Externally published	Yes

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De Bruijne, J., Van De Wetering De Rooij, J., Van Vliet, A. A., Zhou, X. J., Temam, M. F., Molles, J., Chen, J., Pietropaolo, K., Sullivan-Bólyai, J. Z., Mayers, & Reesink, H. W. (2012). First-in-human study of the pharmacokinetics and antiviral activity of IDX375, a novel nonnucleoside hepatitis C virus polymerase inhibitor. Antimicrobial Agents and Chemotherapy, 56(8), 4525-4528. https://doi.org/10.1128/AAC.00451-12

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title = "First-in-human study of the pharmacokinetics and antiviral activity of IDX375, a novel nonnucleoside hepatitis C virus polymerase inhibitor",

abstract = "IDX375 is a potent and selective palm-binding nonnucleoside inhibitor of the hepatitis C virus (HCV) genotype 1 polymerase. This first-in-human study evaluated the safety, tolerability, and pharmacokinetics of IDX375 in healthy volunteers, as well as its antiviral activity in HCV-infected patients. IDX375, as a choline salt, was administered for 1 day to 40 healthy male volunteers (25- to 200-mg IDX375-equivalent single ascending doses and a 200-mg twice-daily [BID] dose) and three patients chronically infected with HCV genotype 1 (200 mg BID only). IDX375 was well absorbed and well tolerated by all of the study participants. A single-day 200-mg BID dose resulted in exposure-related anti-HCV activity with maximal 0.5 to 1.1 log10 reductions in plasma HCV RNA. These observations support further clinical investigations of IDX375.",

author = "{De Bruijne}, J. and {Van De Wetering De Rooij}, J. and {Van Vliet}, {A. A.} and Zhou, {X. J.} and Temam, {M. F.} and J. Molles and J. Chen and K. Pietropaolo and Sullivan-B{\'o}lyai, {J. Z.} and Mayers and Reesink, {H. W.}",

year = "2012",

month = aug,

doi = "10.1128/AAC.00451-12",

language = "English",

volume = "56",

pages = "4525--4528",

journal = "Antimicrobial Agents and Chemotherapy",

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De Bruijne, J, Van De Wetering De Rooij, J, Van Vliet, AA, Zhou, XJ, Temam, MF, Molles, J, Chen, J, Pietropaolo, K, Sullivan-Bólyai, JZ, Mayers & Reesink, HW 2012, 'First-in-human study of the pharmacokinetics and antiviral activity of IDX375, a novel nonnucleoside hepatitis C virus polymerase inhibitor', Antimicrobial Agents and Chemotherapy, vol. 56, no. 8, pp. 4525-4528. https://doi.org/10.1128/AAC.00451-12

First-in-human study of the pharmacokinetics and antiviral activity of IDX375, a novel nonnucleoside hepatitis C virus polymerase inhibitor. / De Bruijne, J.; Van De Wetering De Rooij, J.; Van Vliet, A. A. et al.
In: Antimicrobial Agents and Chemotherapy, Vol. 56, No. 8, 08.2012, p. 4525-4528.

Research output: Contribution to journal › Article › Academic › peer-review

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AU - Van De Wetering De Rooij, J.

AU - Van Vliet, A. A.

AU - Zhou, X. J.

AU - Temam, M. F.

AU - Molles, J.

AU - Chen, J.

AU - Pietropaolo, K.

AU - Sullivan-Bólyai, J. Z.

AU - Mayers,

AU - Reesink, H. W.

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AB - IDX375 is a potent and selective palm-binding nonnucleoside inhibitor of the hepatitis C virus (HCV) genotype 1 polymerase. This first-in-human study evaluated the safety, tolerability, and pharmacokinetics of IDX375 in healthy volunteers, as well as its antiviral activity in HCV-infected patients. IDX375, as a choline salt, was administered for 1 day to 40 healthy male volunteers (25- to 200-mg IDX375-equivalent single ascending doses and a 200-mg twice-daily [BID] dose) and three patients chronically infected with HCV genotype 1 (200 mg BID only). IDX375 was well absorbed and well tolerated by all of the study participants. A single-day 200-mg BID dose resulted in exposure-related anti-HCV activity with maximal 0.5 to 1.1 log10 reductions in plasma HCV RNA. These observations support further clinical investigations of IDX375.

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ER -

First-in-human study of the pharmacokinetics and antiviral activity of IDX375, a novel nonnucleoside hepatitis C virus polymerase inhibitor

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