Multiple ascending dose study of BMS-790052, a nonstructural protein 5A replication complex inhibitor, in patients infected with hepatitis C virus genotype 1

Hepatology

Volumn 54, Issue 6, 2011, Pages 1956-1965

  Nettles, Richard E ^a   Gao, Min ^a   Bifano, Marc ^a   Chung, Ellen ^a   Persson, Anna ^a   Marbury, Thomas C ^b   Goldwater, Ronald ^c   Demicco, Michael P ^d   Rodriguez Torres, Maribel ^e   Vutikullird, Apinya ^f   Fuentes, Ernesto ^g   Lawitz, Eric ^h   Lopez Talavera, Juan Carlos ^a   Grasela, Dennis M ^a  

^a BRISTOL MYERS SQUIBB   (United States)

^b ORLANDO CLINICAL RESEARCH CENTER   (United States)

^c PAREXEL INTERNATIONAL   (United States)

^d Advanced Clinical Research Institute   (United States)

^e Fundacion de Investigacion de Diego   (Puerto Rico)

^f West Coast Clinical Trials LLC   (United States)

^g Elite Research Institute   (United States)

^h Alamo Medical Research   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BMS 790052; NONSTRUCTURAL PROTEIN 5A; PROTEIN INHIBITOR; UNCLASSIFIED DRUG;

ABDOMINAL PAIN; ADULT; ANTIVIRAL ACTIVITY; ARTICLE; BACKACHE; CLINICAL ARTICLE; DIARRHEA; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; FATIGUE; FEMALE; HEADACHE; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; IN VITRO STUDY; INSOMNIA; MALE; MONOTHERAPY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; TREATMENT DURATION; VIRUS INHIBITION; VIRUS REPLICATION;

ADOLESCENT; ADULT; ANTIVIRAL AGENTS; DOUBLE-BLIND METHOD; FEMALE; HALF-LIFE; HEPACIVIRUS; HEPATITIS C, CHRONIC; HUMANS; IMIDAZOLES; MALE; MIDDLE AGED; RNA, VIRAL; VIRAL LOAD; VIRAL NONSTRUCTURAL PROTEINS;

EID: 82455188181     PISSN: 02709139     EISSN: 15273350     Source Type: Journal    
DOI: 10.1002/hep.24609     Document Type: Article

References (14)

1. Ghany MG, Strader DB, Thomas DL, Seeff LB, American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. HEPATOLOGY 2009; 49: 1335-1374.
2. Kwong AD, McNair L, Jacobson I, George S. Recent progress in the development of selected hepatitis C virus NS3.4A protease and NS5B polymerase inhibitors. Curr Opin Pharmacol 2008; 8: 522-531.
3. Kwo PY, Lawitz EJ, McCone J, Schiff ER, Vierling JM, Pound D, et al. Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial. Lancet 2010; 376: 705-716.
4. Jacobson IM, McHutchison JG, Dusheiko GM, Di Bisceglie AM, Reddy R, Bzowej NH, et al. Telaprevir in combination with peginterferon and ribavirin in genotype 1 HCV treatment-naïve patients: final results of phase 3 ADVANCE study. HEPATOLOGY 2010; 52( Suppl S1): 427A [Abstract 211].
5. Fridell RA, Qiu D, Wang C, Valera L, Gao M. Resistance analysis of the hepatitis C virus NS5A inhibitor BMS-790052 in an in vitro replicon system. Antimicrob Agents Chemother 2010; 54: 3641-3650.
6. Gao M, Nettles RE, Belema M, Snyder LB, Nguyen VN, Fridell RA, Serrano-Wu MH, et al. Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature 2010; 465: 96-100.
7. Reesink HW, Zeuzem S, Weegink CJ, Forestier N, van Vliet A, van de Wetering de Rooij J, et al. Rapid decline of viral RNA in hepatitis C patients treated with VX-950: a phase 1b, placebo-controlled, randomized study. Gastroenterology 2006; 131: 997-1002.
8. Gane EJ, Roberts SK, Stedman CA, Angus PW, Ritchie B, Elston R, et al. Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet 2010; 376: 1467-1475.
9. Neumann AU, Lam NP, Dahari H, Gretch DR, Wiley TE, Layden TJ, et al. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science 1998; 282: 103-107.
10. Dahari H, Guedj J, Cotler SJ, Layden TJ, Perelson AS. Higher hepatitis C virus (HCV) clearance rates during treatment with direct acting agents compared to interferon-alpha. HEPATOLOGY 2010; 52( Suppl S1): 718A [Abstract 826].
11. Forestier N, Reesink HW, Weegink CJ, McNair L, Kieffer TL, Chu HM, et al. Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C. HEPATOLOGY 2007; 46: 640-648.
12. Pol S, Everson G, Ghalib R, Rustgi V, Martorell C, Tatum HA, et al. Once-daily NS5A inhibitor (BMS-790052) plus peginterferon-alpha-2A and ribavirin produces high rates of extended rapid virologic response in treatment-naive HCV-genotype 1 subjects: Phase 2A trial. J Hepatol 2010; 52( Suppl 1): S462 [Abstract 1189].
13. Lok AS, Gardiner DF, Lawitz E, Martorell C, Everson GT, Ghalib RH, et al. Combination therapy with BMS-790052 and BMS-650032 alone or with pegIFN/RBV results in undetectable HCV RNA through 12 weeks of therapy in HCV genotype 1 null responders. HEPATOLOGY 2010; 52( Suppl S1): 223A [Abstract LB-8].
14. Macdonald A, Harris M. Hepatitis C virus NS5A: tales of a promiscuous protein. J Gen Virol 2004; 85: 2485-2502.