HCVerso3: An Open-Label, Phase IIb Study of Faldaprevir and Deleobuvir with Ribavirin in Hepatitis C Virus Genotype-1b-Infected Patients with Cirrhosis and Moderate Hepatic Impairment
This study evaluated the interferon-free, oral combination of deleobuvir (non-nucleoside HCV NS5-RNA-polymerase inhibitor) and faldaprevir (HCV NS3/4A-protease inhibitor) with ribavirin in patients with HCV genotype-1b and moderate (Child-Pugh B [CPB], n = 17) or mild hepatic impairment (Child-Pugh...
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| Veröffentlicht in: | PloS one 2016-12, Vol.11 (12), p.e0168544 |
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| creator | Sarrazin, Christoph Manns, Michael Calleja, Jose Luis Garcia-Samaniego, Javier Forns, Xavier Kaste, Renee Bai, Xiaofei Wu, Jing Stern, Jerry O |
| description | This study evaluated the interferon-free, oral combination of deleobuvir (non-nucleoside HCV NS5-RNA-polymerase inhibitor) and faldaprevir (HCV NS3/4A-protease inhibitor) with ribavirin in patients with HCV genotype-1b and moderate (Child-Pugh B [CPB], n = 17) or mild hepatic impairment (Child-Pugh A [CPA], n = 18). Patients received faldaprevir 120 mg and deleobuvir (600 mg [CPA], 400 mg [CPB]) twice-daily with weight-based ribavirin for 24 weeks. Baseline characteristics were similar between groups. Among CPA patients, 13/18 completed treatment; discontinuations were for adverse events (AEs, n = 1), lack of efficacy (n = 3) and withdrawal (n = 1). Among CPB patients, 8/17 completed treatment; discontinuations were for AEs (n = 6), withdrawal (n = 1) and 'other' (n = 2). Sustained virologic response at post-treatment Week 12 (SVR12) was achieved by 11 (61%) CPA patients (95% confidence interval: 38.6%-83.6%) and 9 (53%) CPB patients (95% confidence interval: 29.2%-76.7%), including most CPA (11/16) patients with Week 4 HCV RNA |
| doi_str_mv | 10.1371/journal.pone.0168544 |
| format | Article |
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ClinicalTrials.gov NCT01830127.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0168544</identifier><identifier>PMID: 28030579</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acrylates - therapeutic use ; Adolescent ; Adult ; Aged ; Antiviral Agents - therapeutic use ; Antiviral drugs ; Assaigs clínics ; Benzimidazoles - therapeutic use ; Biological response modifiers ; Biology and life sciences ; Care and treatment ; Cirrhosis ; Cirrosi hepàtica ; Clinical trials ; Confidence intervals ; Diagnosis ; Diarrhea ; DNA-directed RNA polymerase ; Dosage and administration ; Drug Therapy, Combination ; Effectiveness ; Female ; Follow-Up Studies ; Genetic aspects ; Genotype ; Genotype & phenotype ; Genotypes ; Health aspects ; Hepacivirus - genetics ; Hepatic cirrhosis ; Hepatitis ; Hepatitis C ; Hepatitis C virus ; Hepatitis C, Chronic - complications ; Hepatitis C, Chronic - drug therapy ; Hepatitis C, Chronic - virology ; Humans ; Impairment ; Infections ; Interferon ; Liver ; Liver cirrhosis ; Liver Cirrhosis - complications ; Liver Cirrhosis - drug therapy ; Liver Cirrhosis - virology ; Liver diseases ; Malalties del fetge ; Male ; Medicine and health sciences ; Middle Aged ; Nausea ; Oligopeptides - therapeutic use ; Patients ; Pharmaceuticals ; Prognosis ; Protease inhibitors ; Proteinase inhibitors ; Research and Analysis Methods ; Ribavirin ; Ribavirin - therapeutic use ; Ribonucleic acid ; RNA ; RNA polymerase ; RNA, Viral - genetics ; Safety ; Studies ; Target detection ; Thiazoles - therapeutic use ; Viral Load ; Virus de l'hepatitis C ; Viruses ; Vomiting ; Young Adult</subject><ispartof>PloS one, 2016-12, Vol.11 (12), p.e0168544</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Sarrazin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>cc-by (c) Sarrazin, Christoph et al., 2016 info:eu-repo/semantics/openAccess <a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a></rights><rights>2016 Sarrazin et al 2016 Sarrazin et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c767t-34e4e06a57a5b056823238c761de7410698ce73145e8cd9c4c3a7b97c53d47bf3</citedby><cites>FETCH-LOGICAL-c767t-34e4e06a57a5b056823238c761de7410698ce73145e8cd9c4c3a7b97c53d47bf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5193411/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5193411/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,26951,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28030579$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sarrazin, Christoph</creatorcontrib><creatorcontrib>Manns, Michael</creatorcontrib><creatorcontrib>Calleja, Jose Luis</creatorcontrib><creatorcontrib>Garcia-Samaniego, Javier</creatorcontrib><creatorcontrib>Forns, Xavier</creatorcontrib><creatorcontrib>Kaste, Renee</creatorcontrib><creatorcontrib>Bai, Xiaofei</creatorcontrib><creatorcontrib>Wu, Jing</creatorcontrib><creatorcontrib>Stern, Jerry O</creatorcontrib><title>HCVerso3: An Open-Label, Phase IIb Study of Faldaprevir and Deleobuvir with Ribavirin in Hepatitis C Virus Genotype-1b-Infected Patients with Cirrhosis and Moderate Hepatic Impairment</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>This study evaluated the interferon-free, oral combination of deleobuvir (non-nucleoside HCV NS5-RNA-polymerase inhibitor) and faldaprevir (HCV NS3/4A-protease inhibitor) with ribavirin in patients with HCV genotype-1b and moderate (Child-Pugh B [CPB], n = 17) or mild hepatic impairment (Child-Pugh A [CPA], n = 18). Patients received faldaprevir 120 mg and deleobuvir (600 mg [CPA], 400 mg [CPB]) twice-daily with weight-based ribavirin for 24 weeks. Baseline characteristics were similar between groups. Among CPA patients, 13/18 completed treatment; discontinuations were for adverse events (AEs, n = 1), lack of efficacy (n = 3) and withdrawal (n = 1). Among CPB patients, 8/17 completed treatment; discontinuations were for AEs (n = 6), withdrawal (n = 1) and 'other' (n = 2). Sustained virologic response at post-treatment Week 12 (SVR12) was achieved by 11 (61%) CPA patients (95% confidence interval: 38.6%-83.6%) and 9 (53%) CPB patients (95% confidence interval: 29.2%-76.7%), including most CPA (11/16) patients with Week 4 HCV RNA <25 IU.mL-1 (target detected or not detected) and most CPB (8/9) patients with Week 4 HCV RNA <25 IU.mL-1 (target not detected); 0/4 CPB patients with Week 4 HCV RNA <25 IU.mL-1 (target detected) achieved SVR12. The most common AEs in both groups were nausea, diarrhoea and vomiting. Serious AEs were observed in 9 (53%) CPB patients and 1 (6%) CPA patient. Plasma trough concentrations of deleobuvir and faldaprevir were not substantially different between the CPA and CPB groups. In conclusion, in this small study the safety and efficacy profiles for 24 weeks of treatment with faldaprevir+deleobuvir+ribavirin in patients with mild or moderate hepatic impairment were consistent with the safety and efficacy profile of this regimen in non-cirrhotic patients. Faldaprevir+deleobuvir+ribavirin resulted in SVR12 in 53-61% of patients: proportions achieving SVR4 but not SVR12 were higher than in non-cirrhotic patients and overall response rates were lower than rates reported with other all-oral regimens in patients with cirrhosis.
ClinicalTrials.gov NCT01830127.</description><subject>Acrylates - therapeutic use</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Antiviral drugs</subject><subject>Assaigs clínics</subject><subject>Benzimidazoles - therapeutic use</subject><subject>Biological response modifiers</subject><subject>Biology and life sciences</subject><subject>Care and treatment</subject><subject>Cirrhosis</subject><subject>Cirrosi hepàtica</subject><subject>Clinical trials</subject><subject>Confidence intervals</subject><subject>Diagnosis</subject><subject>Diarrhea</subject><subject>DNA-directed RNA polymerase</subject><subject>Dosage and administration</subject><subject>Drug Therapy, Combination</subject><subject>Effectiveness</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Genetic aspects</subject><subject>Genotype</subject><subject>Genotype & phenotype</subject><subject>Genotypes</subject><subject>Health aspects</subject><subject>Hepacivirus - genetics</subject><subject>Hepatic cirrhosis</subject><subject>Hepatitis</subject><subject>Hepatitis C</subject><subject>Hepatitis C virus</subject><subject>Hepatitis C, Chronic - complications</subject><subject>Hepatitis C, Chronic - drug therapy</subject><subject>Hepatitis C, Chronic - virology</subject><subject>Humans</subject><subject>Impairment</subject><subject>Infections</subject><subject>Interferon</subject><subject>Liver</subject><subject>Liver cirrhosis</subject><subject>Liver Cirrhosis - complications</subject><subject>Liver Cirrhosis - drug therapy</subject><subject>Liver Cirrhosis - virology</subject><subject>Liver diseases</subject><subject>Malalties del fetge</subject><subject>Male</subject><subject>Medicine and health sciences</subject><subject>Middle Aged</subject><subject>Nausea</subject><subject>Oligopeptides - therapeutic use</subject><subject>Patients</subject><subject>Pharmaceuticals</subject><subject>Prognosis</subject><subject>Protease inhibitors</subject><subject>Proteinase inhibitors</subject><subject>Research and Analysis Methods</subject><subject>Ribavirin</subject><subject>Ribavirin - therapeutic use</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA polymerase</subject><subject>RNA, Viral - genetics</subject><subject>Safety</subject><subject>Studies</subject><subject>Target detection</subject><subject>Thiazoles - therapeutic use</subject><subject>Viral Load</subject><subject>Virus de l'hepatitis C</subject><subject>Viruses</subject><subject>Vomiting</subject><subject>Young Adult</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>XX2</sourceid><sourceid>DOA</sourceid><recordid>eNqNk2Fr1TAUhosobk7_gWhAEAXvtWmSJvWDMK5uK0w2Nt3XkKan92b0NjVJp_tl_j3T3W7syj5IW9okz_vm5JyeJHmJ0zkmHH-8tIPrVDvvbQfzFOeCUfoo2cUFyWZ5lpLH9753kmfeX6YpIyLPnyY7mUhJynixm_w5WlyA85Z8QvsdOumhmx2rCtoP6HSlPKCyrNB5GOprZBt0oNpa9Q6ujEOqq9EXaMFWwzj8ZcIKnZlKxYHpULyPoFfBBOPRAl0YN3h0CJ0N1z3McDUruwZ0gBqdRgi64DcOC-PcyvooGv2_2RqcCjB5aVSue2XcOvLPkyeNaj28mN57yY-Dr98XR7Pjk8NysX880zznYUYoUEhzxbhiVcpykZGMiLiGa-AUp3khNHCCKQOh60JTTRSvCq4ZqSmvGrKXvN749q31csq5l1gwEmW8wJEoN0Rt1aXsnVkrdy2tMvJmwrqlVC4G34JkTVXjPOOCU0KbSisc41M5S1WlSMFZ9Po87TZUa6h1PKhT7Zbp9kpnVnJprySLpaZ4DAZvDLQftHSgwWkVboR3g_HJUp5JwjJCi6h5N23q7M8BfJBr4zW0rerADjdnLagQBeYRffMP-nBGJmqp4qFN19gYqx5N5T7lLBOCiZGaP0DFq4a10fGnbkyc3xK83xJEJsDvsFSD97I8P_t_9uRim317j12BasPK23YIxnZ-G6RTcp313kFzVxicyrEnb7Mhx56UU09G2av7Rb0T3TYh-Qv3iTGR</recordid><startdate>20161228</startdate><enddate>20161228</enddate><creator>Sarrazin, Christoph</creator><creator>Manns, Michael</creator><creator>Calleja, Jose Luis</creator><creator>Garcia-Samaniego, Javier</creator><creator>Forns, Xavier</creator><creator>Kaste, Renee</creator><creator>Bai, Xiaofei</creator><creator>Wu, Jing</creator><creator>Stern, Jerry O</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>XX2</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20161228</creationdate><title>HCVerso3: An Open-Label, Phase IIb Study of Faldaprevir and Deleobuvir with Ribavirin in Hepatitis C Virus Genotype-1b-Infected Patients with Cirrhosis and Moderate Hepatic Impairment</title><author>Sarrazin, Christoph ; Manns, Michael ; Calleja, Jose Luis ; Garcia-Samaniego, Javier ; Forns, Xavier ; Kaste, Renee ; Bai, Xiaofei ; Wu, Jing ; Stern, Jerry O</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c767t-34e4e06a57a5b056823238c761de7410698ce73145e8cd9c4c3a7b97c53d47bf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Acrylates - therapeutic use</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Antiviral drugs</topic><topic>Assaigs clínics</topic><topic>Benzimidazoles - therapeutic use</topic><topic>Biological response modifiers</topic><topic>Biology and life sciences</topic><topic>Care and treatment</topic><topic>Cirrhosis</topic><topic>Cirrosi hepàtica</topic><topic>Clinical trials</topic><topic>Confidence intervals</topic><topic>Diagnosis</topic><topic>Diarrhea</topic><topic>DNA-directed RNA polymerase</topic><topic>Dosage and administration</topic><topic>Drug Therapy, Combination</topic><topic>Effectiveness</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Genetic aspects</topic><topic>Genotype</topic><topic>Genotype & phenotype</topic><topic>Genotypes</topic><topic>Health aspects</topic><topic>Hepacivirus - genetics</topic><topic>Hepatic cirrhosis</topic><topic>Hepatitis</topic><topic>Hepatitis C</topic><topic>Hepatitis C virus</topic><topic>Hepatitis C, Chronic - complications</topic><topic>Hepatitis C, Chronic - drug therapy</topic><topic>Hepatitis C, Chronic - virology</topic><topic>Humans</topic><topic>Impairment</topic><topic>Infections</topic><topic>Interferon</topic><topic>Liver</topic><topic>Liver cirrhosis</topic><topic>Liver Cirrhosis - complications</topic><topic>Liver Cirrhosis - drug therapy</topic><topic>Liver Cirrhosis - virology</topic><topic>Liver diseases</topic><topic>Malalties del fetge</topic><topic>Male</topic><topic>Medicine and health sciences</topic><topic>Middle Aged</topic><topic>Nausea</topic><topic>Oligopeptides - therapeutic use</topic><topic>Patients</topic><topic>Pharmaceuticals</topic><topic>Prognosis</topic><topic>Protease inhibitors</topic><topic>Proteinase inhibitors</topic><topic>Research and Analysis Methods</topic><topic>Ribavirin</topic><topic>Ribavirin - therapeutic use</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA polymerase</topic><topic>RNA, Viral - genetics</topic><topic>Safety</topic><topic>Studies</topic><topic>Target detection</topic><topic>Thiazoles - therapeutic use</topic><topic>Viral Load</topic><topic>Virus de l'hepatitis C</topic><topic>Viruses</topic><topic>Vomiting</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sarrazin, Christoph</creatorcontrib><creatorcontrib>Manns, Michael</creatorcontrib><creatorcontrib>Calleja, Jose Luis</creatorcontrib><creatorcontrib>Garcia-Samaniego, Javier</creatorcontrib><creatorcontrib>Forns, Xavier</creatorcontrib><creatorcontrib>Kaste, Renee</creatorcontrib><creatorcontrib>Bai, Xiaofei</creatorcontrib><creatorcontrib>Wu, Jing</creatorcontrib><creatorcontrib>Stern, Jerry O</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>Recercat</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sarrazin, Christoph</au><au>Manns, Michael</au><au>Calleja, Jose Luis</au><au>Garcia-Samaniego, Javier</au><au>Forns, Xavier</au><au>Kaste, Renee</au><au>Bai, Xiaofei</au><au>Wu, Jing</au><au>Stern, Jerry O</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>HCVerso3: An Open-Label, Phase IIb Study of Faldaprevir and Deleobuvir with Ribavirin in Hepatitis C Virus Genotype-1b-Infected Patients with Cirrhosis and Moderate Hepatic Impairment</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-12-28</date><risdate>2016</risdate><volume>11</volume><issue>12</issue><spage>e0168544</spage><pages>e0168544-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>This study evaluated the interferon-free, oral combination of deleobuvir (non-nucleoside HCV NS5-RNA-polymerase inhibitor) and faldaprevir (HCV NS3/4A-protease inhibitor) with ribavirin in patients with HCV genotype-1b and moderate (Child-Pugh B [CPB], n = 17) or mild hepatic impairment (Child-Pugh A [CPA], n = 18). Patients received faldaprevir 120 mg and deleobuvir (600 mg [CPA], 400 mg [CPB]) twice-daily with weight-based ribavirin for 24 weeks. Baseline characteristics were similar between groups. Among CPA patients, 13/18 completed treatment; discontinuations were for adverse events (AEs, n = 1), lack of efficacy (n = 3) and withdrawal (n = 1). Among CPB patients, 8/17 completed treatment; discontinuations were for AEs (n = 6), withdrawal (n = 1) and 'other' (n = 2). Sustained virologic response at post-treatment Week 12 (SVR12) was achieved by 11 (61%) CPA patients (95% confidence interval: 38.6%-83.6%) and 9 (53%) CPB patients (95% confidence interval: 29.2%-76.7%), including most CPA (11/16) patients with Week 4 HCV RNA <25 IU.mL-1 (target detected or not detected) and most CPB (8/9) patients with Week 4 HCV RNA <25 IU.mL-1 (target not detected); 0/4 CPB patients with Week 4 HCV RNA <25 IU.mL-1 (target detected) achieved SVR12. The most common AEs in both groups were nausea, diarrhoea and vomiting. Serious AEs were observed in 9 (53%) CPB patients and 1 (6%) CPA patient. Plasma trough concentrations of deleobuvir and faldaprevir were not substantially different between the CPA and CPB groups. In conclusion, in this small study the safety and efficacy profiles for 24 weeks of treatment with faldaprevir+deleobuvir+ribavirin in patients with mild or moderate hepatic impairment were consistent with the safety and efficacy profile of this regimen in non-cirrhotic patients. Faldaprevir+deleobuvir+ribavirin resulted in SVR12 in 53-61% of patients: proportions achieving SVR4 but not SVR12 were higher than in non-cirrhotic patients and overall response rates were lower than rates reported with other all-oral regimens in patients with cirrhosis.
ClinicalTrials.gov NCT01830127.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28030579</pmid><doi>10.1371/journal.pone.0168544</doi><tpages>e0168544</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-12, Vol.11 (12), p.e0168544 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1853731791 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Recercat; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Acrylates - therapeutic use Adolescent Adult Aged Antiviral Agents - therapeutic use Antiviral drugs Assaigs clínics Benzimidazoles - therapeutic use Biological response modifiers Biology and life sciences Care and treatment Cirrhosis Cirrosi hepàtica Clinical trials Confidence intervals Diagnosis Diarrhea DNA-directed RNA polymerase Dosage and administration Drug Therapy, Combination Effectiveness Female Follow-Up Studies Genetic aspects Genotype Genotype & phenotype Genotypes Health aspects Hepacivirus - genetics Hepatic cirrhosis Hepatitis Hepatitis C Hepatitis C virus Hepatitis C, Chronic - complications Hepatitis C, Chronic - drug therapy Hepatitis C, Chronic - virology Humans Impairment Infections Interferon Liver Liver cirrhosis Liver Cirrhosis - complications Liver Cirrhosis - drug therapy Liver Cirrhosis - virology Liver diseases Malalties del fetge Male Medicine and health sciences Middle Aged Nausea Oligopeptides - therapeutic use Patients Pharmaceuticals Prognosis Protease inhibitors Proteinase inhibitors Research and Analysis Methods Ribavirin Ribavirin - therapeutic use Ribonucleic acid RNA RNA polymerase RNA, Viral - genetics Safety Studies Target detection Thiazoles - therapeutic use Viral Load Virus de l'hepatitis C Viruses Vomiting Young Adult |
| title | HCVerso3: An Open-Label, Phase IIb Study of Faldaprevir and Deleobuvir with Ribavirin in Hepatitis C Virus Genotype-1b-Infected Patients with Cirrhosis and Moderate Hepatic Impairment |
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