Efficacy and safety of a two-drug direct-acting antiviral agent regimen ruzasvir 180 mg and uprifosbuvir 450 mg for 12 weeks in adults with chronic...
Lawitz E., Gane E., Feld J. J., Buti M., Foster G. R., Rabinovitz M., Burnevich E`. Z., Katchman H., Tomasiewicz K., Lahser F., Jackson B., Shaughnessy M., Klopfer S., Yeh W. W., Robertson M. N., Hanna G. J., Barr E., Platt H. L., Gordon S. C., Lawitz E. J., Ruane P. J., Sahota A., Terrault N. A., Tsai N., Kalathil S. C., Reddy G., Ghesquiere W., Borgia S., Conway B., Feld J., Tsoi K., Cooper C. L., Ghali P. M., Thompson A. J. V., Panero J. L. C., Ferret S. L. M. B., Franinan L. M., de l. A. C. I. M., Brown A., Agarwal K., Foster G., Cramp M., Zuckerman E., Veitsman E., Cohen M., Lurie Y., Ari Z. B., Janczewska E., Szymczak A., Halota W., Flisiak R., Mahomed A., Sonderup M. W., Punt Z. E., Kgomo M. K., Bernhardi D. C., Kizhlo S.
Journal of Viral Hepatitis
Vol.26, Issue9, P. 1127-1138
Опубликовано: 2019
Тип ресурса: Статья
Аннотация:
Ruzasvir (MK-8408, an NS5A inhibitor) and uprifosbuvir (MK-3682, a nonstructural protein 5B nucleotide inhibitor) are highly potent direct-acting antiviral agents for the treatment of hepatitis C virus (HCV) infection. A phase III clinical trial evaluating the two-drug combination of ruzasvir 60 mg plus uprifosbuvir 450 mg suggested suboptimal efficacy in certain HCV genotypes (C-BREEZE 1; NCT02759315). The aim of the present study was to evaluate the efficacy and safety of ruzasvir in combination with uprifosbuvir administered at a higher dose than that assessed in the earlier study (C-BREEZE 2: NCT02956629/Merck protocol PN041). Treatment-naïve or interferon (with or without ribavirin)-experienced participants with or without compensated cirrhosis were enrolled. All participants received ruzasvir 180 mg plus uprifosbuvir 450 mg once daily for 12 weeks. The primary objectives were the proportion of participants with HCV RNA <15 lU/mL at 12 weeks after the end of study therapy (SVR12),
Ключевые слова:
clinical trial; efficacy; genotype; hepatitis C virus; safety
ruzasvir; uprifosbuvir; virus RNA; antivirus agent; fused heterocyclic rings; interferon; pyrrolidine derivative; ribavirin; ruzasvir; thiazole derivative; uprifosbuvir; uridine; abdominal pain; adult; aged; anxiety disorder; Article; chronic hepatitis C; diarrhea; drug efficacy; drug safety; drug tolerability; drug withdrawal; fatigue; female; headache; Hepatitis C virus genotype 1; Hepatitis C virus genotype 2; Hepatitis C virus genotype 3; Hepatitis C virus genotype 4; Hepatitis C virus genotype 5; Hepatitis C virus genotype 6; human; insomnia; liver cirrhosis; major clinical study; male; nausea; phase 2 clinical trial; priority journal; very elderly; blood; chronic hepatitis C; clinical trial; combination drug therapy; drug administration; drug effect; genetics; genotype; Hepacivirus; middle aged; sustained virologic response; young adult; Adult; Aged; Aged, 80 and over; Antiviral Agents; Drug Administration Schedule; Drug Therapy, Combination; Female; Genotype; Hepacivirus; Hepati
Язык текста: Английский
ISSN: 1365-2893
Lawitz E.
Gane E.
Feld J. J.
Buti M.
Foster G. R.
Rabinovitz M.
Burnevich E`. Z. E`duard Zbignevich 1972-
Katchman H.
Tomasiewicz K.
Lahser F.
Jackson B.
Shaughnessy M.
Klopfer S.
Yeh W. W.
Robertson M. N.
Hanna G. J.
Barr E.
Platt H. L.
Gordon S. C.
Lawitz E. J.
Ruane P. J.
Sahota A.
Terrault N. A.
Tsai N.
Kalathil S. C.
Reddy G.
Ghesquiere W.
Borgia S.
Conway B.
Feld J.
Tsoi K.
Cooper C. L.
Ghali P. M.
Thompson A. J. V.
Panero J. L. C.
Ferret S. L. M. B.
Franinan L. M.
de l. A. C. I. M. los Angeles Castro Iglesias M.
Brown A.
Agarwal K.
Foster G.
Cramp M.
Zuckerman E.
Veitsman E.
Cohen M.
Lurie Y.
Ari Z. B.
Janczewska E.
Szymczak A.
Halota W.
Flisiak R.
Mahomed A.
Sonderup M. W.
Punt Z. E.
Kgomo M. K.
Bernhardi D. C.
Kizhlo S.
Лаwитз Е.
Гане Е.
Фелд Й. Й.
Бути М.
Фостер Г. Р.
Рабиновитз М.
Бурневич Э. З. Эдуард Збигневич 1972-
Катчман Х.
Томасиеwиcз К.
Лахсер Ф.
Йаcксон Б.
Шаугхнессy М.
Клопфер С.
Ьех W. W.
Роберцон М. Н.
Ханна Г. Й.
Барр Е.
Платт Х. Л.
Гордон С. C.
Лаwитз Е. Й.
Руане П. Й.
Сахота А.
Терраулт Н. А.
Цаи Н.
Калатхил С. C.
Реддy Г.
Гхесqуиере W.
Боргиа С.
Cонwай Б.
Фелд Й.
Цои К.
Cоопер C. Л.
Гхали П. М.
Тхомпсон А. Й. В.
Панеро Й. Л. C.
Феррет С. Л. М. Б.
Франинан Л. М.
де л. А. C. И. М. лос Ангелес Cастро Иглесиас М.
Броwн А.
Агарwал К.
Фостер Г.
Cрамп М.
Зуcкерман Е.
Веицман Е.
Cохен М.
Лурие Y.
Ари З. Б.
Йанcзеwска Е.
Сзyмcзак А.
Халота W.
Флисиак Р.
Махомед А.
Сондеруп М. W.
Пунт З. Е.
Кгомо М. К.
Бернхарди Д. C.
Кижло С.
Efficacy and safety of a two-drug direct-acting antiviral agent regimen ruzasvir 180 mg and uprifosbuvir 450 mg for 12 weeks in adults with chronic hepatitis C virus genotype 1, 2, 3, 4, 5 or 6
Efficacy and safety of a two-drug direct-acting antiviral agent regimen ruzasvir 180 mg and uprifosbuvir 450 mg for 12 weeks in adults with chronic...
Текст визуальный непосредственный
Journal of Viral Hepatitis
John Wiley & Sons, Inc.
Vol.26, Issue9 P. 1127-1138
2019
Статья
clinical trial efficacy genotype hepatitis C virus safety
ruzasvir uprifosbuvir virus RNA antivirus agent fused heterocyclic rings interferon pyrrolidine derivative ribavirin ruzasvir thiazole derivative uprifosbuvir uridine abdominal pain adult aged anxiety disorder Article chronic hepatitis C diarrhea drug efficacy drug safety drug tolerability drug withdrawal fatigue female headache Hepatitis C virus genotype 1 Hepatitis C virus genotype 2 Hepatitis C virus genotype 3 Hepatitis C virus genotype 4 Hepatitis C virus genotype 5 Hepatitis C virus genotype 6 human insomnia liver cirrhosis major clinical study male nausea phase 2 clinical trial priority journal very elderly blood chronic hepatitis C clinical trial combination drug therapy drug administration drug effect genetics genotype Hepacivirus middle aged sustained virologic response young adult Adult Aged Aged, 80 and over Antiviral Agents Drug Administration Schedule Drug Therapy, Combination Female Genotype Hepacivirus Hepati
Ruzasvir (MK-8408, an NS5A inhibitor) and uprifosbuvir (MK-3682, a nonstructural protein 5B nucleotide inhibitor) are highly potent direct-acting antiviral agents for the treatment of hepatitis C virus (HCV) infection. A phase III clinical trial evaluating the two-drug combination of ruzasvir 60 mg plus uprifosbuvir 450 mg suggested suboptimal efficacy in certain HCV genotypes (C-BREEZE 1; NCT02759315). The aim of the present study was to evaluate the efficacy and safety of ruzasvir in combination with uprifosbuvir administered at a higher dose than that assessed in the earlier study (C-BREEZE 2: NCT02956629/Merck protocol PN041). Treatment-naïve or interferon (with or without ribavirin)-experienced participants with or without compensated cirrhosis were enrolled. All participants received ruzasvir 180 mg plus uprifosbuvir 450 mg once daily for 12 weeks. The primary objectives were the proportion of participants with HCV RNA <15 lU/mL at 12 weeks after the end of study therapy (SVR12),