Fixed-Dose Combination Therapy With Daclatasvir, Asunaprevir, and Beclabuvir for Noncirrhotic Patients With HCV Genotype 1 Infection
| Autor: | Michael R Bennett, Edward Tam, Edmund Tse, Brian Conway, Fred Poordad, Victor de Ledinghen, Samuel S. Lee, Grisell Ortiz-Lasanta, Navdeep Boparai, Philip D. Yin, Mark S. Sulkowski, Lindsay Mollison, Fiona McPhee, Norbert Bräu, Andrew J. Muir, Nathalie Boyer, Jean-Pierre Bronowicki, Stanislas Pol, James E. Levin, E. Scott Swenson, Ira M. Jacobson, Peter W Angus, Thomas Sepe, K. Rajender Reddy, William Sievert, Eric Hughes |
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| Přispěvatelé: | Texas Liver Institute [San Antonio], University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth)- The University of Texas Health Science Center at Houston (UTHealth), Monash University [Clayton], School of Medecine and Pharmacology, The University of Western Australia (UWA), Medical Associates Research Group, Royal Adelaide Hospital, James J. Peters VA Medical Center [New York], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Dean Foundation, Brown University, University of Calgary, Austin Hospital [Melbourne], Austin Health, Vancouver Infectious Diseases Centre, Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Weill Medical College of Cornell University [New York], Duke University Medical Center, Pennsylvania State University (Penn State), Penn State System, Lair Centre (Liver Health Centre), Fundacion de Investigacion [San Juan, Puerto Rico] (FDI San Juan), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Johns Hopkins University School of Medicine [Baltimore], Bristol-Myers Squibb [Princeton], Bristol-Myers Squibb Company, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, CHU Bordeaux [Bordeaux]-Université Sciences et Technologies - Bordeaux 1, Bristol-Myers Squibb, Princeton |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Indoles Pyrrolidines Sofosbuvir [SDV]Life Sciences [q-bio] ABT-450/R-Ombitasvir Hepacivirus chemistry.chemical_compound 0302 clinical medicine Beclabuvir ComputingMilieux_MISCELLANEOUS 0303 health sciences Sulfonamides Dasabuvir Hepatitis-C Virus Imidazoles Alanine Transaminase Valine General Medicine Hepatitis C Middle Aged 3. Good health 030211 gastroenterology & hepatology Drug Therapy Combination Female Ledipasvir medicine.drug Adult medicine.medical_specialty Daclatasvir Genotype Plus Asunaprevir Antiviral Agents Treatment-Naive Patients 03 medical and health sciences Internal medicine Ribavirin medicine Humans BMS-791325 030304 developmental biology Aged business.industry Benzazepines Hepatitis C Chronic medicine.disease Isoquinolines Regimen chemistry Immunology Asunaprevir Carbamates business |
| Zdroj: | JAMA Ophthalmology JAMA Ophthalmology, American Medical Association 2015, 313 (17), pp.1728-1735. ⟨10.1001/jama.2015.3860⟩ |
| ISSN: | 2168-6165 2168-6173 |
| DOI: | 10.1001/jama.2015.3860⟩ |
| Popis: | The antiviral activity of all-oral, ribavirin-free, direct-acting antiviral regimens requires evaluation in patients with chronic hepatitis C virus (HCV) infection.To determine the rates of sustained virologic response (SVR) in patients receiving the 3-drug combination of daclatasvir (a pan-genotypic NS5A inhibitor), asunaprevir (an NS3 protease inhibitor), and beclabuvir (a nonnucleoside NS5B inhibitor).This was an open-label, single-group, uncontrolled international study (UNITY-1) conducted at 66 sites in the United States, Canada, France, and Australia between December 2013 and August 2014. Patients without cirrhosis who were either treatment-naive (n = 312) or treatment-experienced (n = 103) and had chronic HCV genotype 1 infection were included.Patients received a twice-daily fixed-dose combination of daclatasvir, 30 mg; asunaprevir, 200 mg; and beclabuvir, 75 mg.The primary study outcome was SVR12 (HCV-RNA25 IU/mL at posttreatment week 12) in patients naive to treatment. A key secondary outcome was SVR12 in the treatment-experienced cohort.Baseline characteristics were comparable between the treatment-naive and treatment-experienced cohorts. Patients were 58% male, 26% had IL28B (rs12979860) CC genotype, 73% were infected with genotype 1a, and 27% were infected with genotype 1b. Overall, SVR12 was observed in 379 of 415 patients (91.3%; 95% CI, 88.6%-94.0%): 287 of 312 treatment-naive patients (92.0%; 95% CI, 89.0%-95.0%) and 92 of 103 treatment-experienced patients (89.3%; 95% CI, 83.4%-95.3%). Virologic failure occurred in 34 patients (8%) overall. One patient died at posttreatment week 3; this was not considered related to study medication. There were 7 serious adverse events, all considered unrelated to study treatment, and 3 adverse events (1%) leading to treatment discontinuation, including 2 grade 4 alanine aminotransferase elevations. The most common adverse events (in ≥10% of patients) were headache, fatigue, diarrhea, and nausea.In this open-label, nonrandomized, uncontrolled study, a high rate of SVR12 was achieved in treatment-naive and treatment-experienced noncirrhotic patients with chronic HCV genotype 1 infection who received 12 weeks of treatment with the oral fixed-dose regimen of daclatasvir, asunaprevir, and beclabuvir.clinicaltrials.gov Identifier: NCT01979939. |
| Databáze: | OpenAIRE |
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