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GSK 2878175, a pan‐genotypic non‐nucleoside NS 5B polymerase inhibitor, in healthy and treatment‐naïve chronic hepatitis C subjects
Author(s) -
Gardner S. D.,
Kim J.,
BaptisteBrown S.,
Lopez V.,
Hamatake R.,
Gan J.,
Edwards S.,
ElkoSimms L.,
Dumont E. F.,
Leivers M.,
Hong Z.,
Paff M. T.
Publication year - 2018
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12753
Subject(s) - medicine , placebo , pharmacokinetics , hepatitis c virus , genotype , hepatitis c , pharmacology , chronic hepatitis , adverse effect , gastroenterology , virus , virology , biology , pathology , alternative medicine , biochemistry , gene
Summary GSK 2878175 is a potent, pan‐genotypic, non‐nucleoside, nonstructural protein 5B palm polymerase inhibitor being developed for the treatment of chronic hepatitis C ( CHC ). A first‐in‐human, randomized, placebo‐controlled, dose escalation study, evaluated the safety and pharmacokinetics of GSK 2878175 administered as single and repeat oral doses (once daily for 14 days) to healthy volunteers. A separate proof‐of‐concept, placebo‐controlled, repeat dose (once daily for 2 days) study evaluated the safety, pharmacokinetics and antiviral activity of GSK 2878175 monotherapy in treatment‐naïve, noncirrhotic, subjects with hepatitis C virus (HCV) genotype 1 [1a and 1b], 2, or 3. No deaths or SAE s were reported in either study, and treatment was well‐tolerated. Across all the HCV genotypes, GSK 2878175 monotherapy at doses of 10, 30 or 60 mg once daily for 2 days produced a statistically significant multilog reduction ( P <.001) in plasma HCV RNA log 10 IU / mL from Baseline to 24, 48 and 72 hours after the first dose of GSK 2878175 compared to placebo. The reduction in HCV RNA was sustained for a prolonged period across all of the active treatment groups, consistent with the long apparent half‐life of GSK 2878175 that was observed (mean t 1/2 range: 60‐63 hours in the CHC subjects). In summary, GSK 2878175, when administered to healthy subjects and subjects with CHC , did not reveal any safety concerns that would limit or preclude further clinical development. GSK 2878175 monotherapy across a wide dose range produced substantial reduction in HCV RNA , irrespective of HCV genotype. The results from these studies support further evaluation of GSK 2878175‐based regimens.