Pharmacokinetics of the ns3 protease inhibitor, asunaprevir (ASV, BMS-650032), in phase i studies in subjects with or without chronic hepatitis c

Clinical Pharmacology in Drug Development

Volumn 2, Issue 4, 2013, Pages 316-327

  Eley, Timothy ^a   He, Bing ^a   Huang, Shu Pang ^a   Li, Wenying ^a   Pasquinelli, Claudio ^a   Rodrigues, A David ^a   Grasela, Dennis M ^a   Bertz, Richard J ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

Asunaprevir; Hepatitis C virus; NS3; Pharmacokinetics

Indexed keywords

ASUNAPREVIR; PLACEBO;

ADULT; AREA UNDER THE CURVE; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG CAPSULE; DRUG CLEARANCE; DRUG DISPOSITION; DRUG DOSE COMPARISON; DRUG DOSE SEQUENCE; DRUG EFFICACY; DRUG EXCRETION; DRUG FORMULATION; DRUG HALF LIFE; DRUG SOLUBILITY; FEMALE; FIRST PASS EFFECT; FOOD DRUG INTERACTION; HEPATITIS C; HUMAN; MALE; MAXIMUM PLASMA CONCENTRATION; PRIORITY JOURNAL; SINGLE DRUG DOSE; STEADY STATE; SUSPENSION; TIME TO MAXIMUM PLASMA CONCENTRATION;

EID: 84885913354     PISSN: 2160763X     EISSN: 21607648     Source Type: Journal    
DOI: 10.1002/cpdd.52     Document Type: Article

References (25)

1. Lavanchy D. Hepatitis B virus epidemiology disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004; 11:97-107.
2. Negro F, Alberti A. The global health burden of hepatitis C virus infection. Liver Int. 2011; 31(suppl 2):1-3.
3. World Health Organization. Hepatitis C key facts. Available from (http://www.who.int/mediacentre/factsheets/fs164/en/). Updated 2011. Accessed December 1, 2011.
4. World Health Organization. Global alert and response (GAR)-hepatitis C. Available from (http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index4.html). Updated 2011. Accessed March 12, 2011.
5. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002; 347:975-982.
6. Hadziyannis SJ, Sette H Jr, Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004; 140:346-355.
7. Hoofnagle JH, Wahed AS, Brown RS Jr, Howell CD, Belle SH, Virahep-C Study Group. Early changes in hepatitis C virus (HCV) levels in response to peginterferon and ribavirin treatment in patients with chronic HCV genotype 1 infection. J Infect Dis. 2009; 199:1112-1120.
8. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001; 358:958-965.
9. Ghany M, Nelson DR, Strader DB, Thomas DL, Seeff LB. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guidelines by the American Association for the Study of Liver Diseases. Hepatology. 2011; 54:1433-1444.
10. McHutchison JG, Lawitz EJ, Shiffman ML, et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009; 361:580-593.
11. Jensen DM, Marcellin P, Freilich B, et al. Re-treatment of patients with chronic hepatitis C who do not respond to peginterferon-alpha2b: a randomized trial. Ann Intern Med. 2009; 150:528-540.
12. Poynard T, Colombo M, Bruix J, et al. Peginterferon alfa-2b and ribavirin: effective in patients with hepatitis C who failed interferon alfa/ribavirin therapy. Gastroenterology. 2009; 136:1618-1628.
13. Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011; 364:2405-2416.
14. Poordad F, McCone J Jr, Bacon BR, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011; 364:1195-1206.
15. Zeuzem S, Andreone P, Pol S, et al. Telaprevir for retreatment of HCV infection. N Engl J Med. 2011; 364:2417-2428.
16. Bacon BR, Gordon SC, Lawitz E, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011; 364:1207-1217.
17. McPhee F, Sheafer AK, Friborg J, et al. Preclinical profile and characterization of the hepatitis C virus NS3 protease inhibitor Asunaprevir (BMS-650032). Antimicrob Agents Chemother. 2012; 56:5387-5396.
18. McPhee F, Sheaffer AK, Freeman JA, et al. In vitro activity of the combination of pegylated interferon-lambda (peg-IFN-λ) with direct-acting antivirals in the HCV replicon model [abstract]. Hepatology. 2010; 52(4 suppl):1201A-1202A.
19. Bronowicki JP, Pol S, Thuluvath PJ, et al. BMS-650032, an NS3 inhibitor, in combination with peginterferon alfa-2a and ribavirin in treatment-naive subjects with genotype 1 chronic hepatitis C infection [abstract]. J Hepatol. 2011; 54(suppl 1):S472.
20. Lok AS, Gardiner DF, Lawitz E, et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med. 2012; 366:216-224.
21. Pasquinelli C, McPhee F, Eley T, et al. Single and multiple ascending dose studies of the NS3 protease inhibitor, asunaprevir, in subjects with or without chronic hepatitis C. Antivir Agents Chemother. 2012; 56:1838-1844.
22. Sebastiani G, Halfon P, Castera L, et al. SAFE biopsy: a validated method for large-scale staging of liver fibrosis in chronic hepatitis C. Hepatology. 2009; 49:1821-1827.
23. Eley T, Gardiner D, Persson A, et al. Evaluation of drug interaction potential of the HCV protease inhibitor asunaprevir (ASV; BMS-650032) at 200mg twice daily (BID) in metabolic cocktail and P-glycoprotein (P-gp) probe studies in healthy volunteers [abstract]. Hepatology. 2011; 54(suppl 1):Abstract 381.
24. Biffano M, Sevinsky H, Bedford B, et al. Coadministration of BMS-790052 and BMS-650032 does not result in a clinically meaningful pharmacokinetic interaction in healthy subjects [abstract]. Hepatology. 2010; 52(suppl 1):Abstract 827.
25. Reddy MB, Morcos PN, Le Pogam S, et al. Pharmacokinetic/pharmacodynamic predictors of clinical potency for hepatitis C virus nonnucleoside polymerase and protease inhibitors. Antimicrob Agents Chemother. 2012; 56:3144-3156.