The pharmacokinetics of daclatasvir and asunaprevir administered in combination in studies in healthy subjects and patients infected with hepatitis C virus

Clinical Drug Investigation

Volumn 34, Issue 9, 2014, Pages 661-671

  Eley, Timothy ^a   Sevinsky, Heather ^a   Huang, Shu Pang ^a   He, Bing ^a   Zhu, Kurt ^a   Kandoussi, Hamza ^a   Gardiner, David ^a   Grasela, Dennis M ^a   Bertz, Richard ^a   Bifano, Marc ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ASUNAPREVIR; DACLATASVIR; PEGINTERFERON ALPHA; RIBAVIRIN; ALPHA INTERFERON; ANTIVIRUS AGENT; BMS-790052; IMIDAZOLE DERIVATIVE; ISOQUINOLINE DERIVATIVE; MACROGOL DERIVATIVE; PEGINTERFERON ALPHA2A; PEGINTERFERON ALPHA2B; RECOMBINANT PROTEIN; SULFONAMIDE;

ADULT; AREA UNDER THE CURVE; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; HUMAN EXPERIMENT; MALE; MAXIMUM PLASMA CONCENTRATION; NORMAL HUMAN; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; TIME TO MAXIMUM PLASMA CONCENTRATION; UNSPECIFIED SIDE EFFECT; CLINICAL TRIAL; COMPARATIVE STUDY; DRUG COMBINATION; DRUG INTERACTION; HEPATITIS C, CHRONIC; MIDDLE AGED; YOUNG ADULT;

ADULT; ANTIVIRAL AGENTS; AREA UNDER CURVE; DRUG INTERACTIONS; DRUG THERAPY, COMBINATION; FEMALE; HEPATITIS C, CHRONIC; HUMANS; IMIDAZOLES; INTERFERON-ALPHA; ISOQUINOLINES; MALE; MIDDLE AGED; POLYETHYLENE GLYCOLS; RECOMBINANT PROTEINS; RIBAVIRIN; SULFONAMIDES; YOUNG ADULT;

EID: 84906775992     PISSN: 11732563     EISSN: 11791918     Source Type: Journal    
DOI: 10.1007/s40261-014-0219-9     Document Type: Article

References (38)

1. Nettles RE, Gao M, Bifano M, Chung E, Persson A, Marbury TC, et al. Multiple ascending dose study of BMS-790052, an NS5A replication complex inhibitor, in patients infected with hepatitis C virus genotype 1. Hepatology. 2011;54(6):1956-65.
2. Gao M, Nettles RE, Belema M, Snyder LB, Nguyen VN, Fridell RA, et al. Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature. 2010;465(7294):96-100.
3. Pelosi LA, Voss S, Liu M, Gao M, Lemm JA. Effect on hepatitis C virus replication of combinations of direct-acting antivirals, including NS5A inhibitor daclatasvir. Antimicrob Agents Chemother. 2012;56(10):5230-9.
4. Friborg J, Levine S, Chen C, Sheaffer AK, Chaniewski S, Voss S, et al. Combinations of lambda interferon with direct-acting antiviral agents are highly efficient in suppressing hepatitis C virus replication. Antimicrob Agents Chemother. 2013;57(3):1312-22.
5. Pol S, Ghalib RH, Rustgi VK, Martorell C, Everson GT, Tatum HA, et al. Daclatasvir for previously untreated chronic hepatitis C genotype 1 infection: a randomised, parallel-group, double-blind, placebo-controlled, dose-finding, phase 2a trial. Lancet Infect Dis. 2012;12(9):671-7.
6. Dore GJ, Lawitz E, Hézode C, Shafran S, Ramji A, Tatum H, et al. Daclatasvir combined with peginterferon alfa-2a and ribavirin for 12 or 16 weeks in patients with HCV genotype 2 or 3 infection: COMMAND GT2/3 study. J Hepatol. 2013;58(Suppl 1):S570-1.
7. Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, Jacobson IM, et al. High rate of sustained virologic response with the all-oral combination of daclatasvir (NS5A inhibitor) plus sofosbuvir (nucleotide NS5B inhibitor), with or without ribavirin, in treatment-naïve patients chronically infected with HCV genotype 1, 2, or 3 [abstract]. Hepatology 2012;56(Suppl 4):abstract LB-02.
8. Everson GT, Sims KD, Rodriguez-Torres M, Hézode C, Lawitz E, Bourlière M, et al. Interim analysis of an interferon (IFN)- and ribavirin (RBV)-free regimen of daclatasvir (DCV), asunaprevir (ASV), and BMS-791325 in treatment-naive, hepatitis C virus genotype 1-infected patients [abstract]. J Hepatol. 2013;58(Suppl 1):S573.
9. Lok A, Gardiner D, Hézode C, Lawitz E, Bourlière M, Everson G, et al. Randomized trial of daclatasvir and asunaprevir with or without peginterferon/ribavirin for hepatitis C virus genotype 1 null responders. J Hepatol. 2014;60(3):490-9.
10. McPhee F, Sheaffer AK, Friborg J, Hernandez D, Falk P, Zhai G, et al. Preclinical profile and characterization of the hepatitis C virus NS3 protease inhibitor asunaprevir (BMS-650032). Antimicrob Agents Chemother. 2012;56(10):5387-96.
11. Suzuki Y, Ikeda K, Suzuki F, Toyota J, Karino Y, Chayama K, et al. Dual oral therapy with daclatasvir and asunaprevir for patients with HCV genotype 1b infection and limited treatment options. J Hepatol. 2013;58(4):655-62.
12. Eley T, Pasquinelli C, Wendelburg P, Villegas C, He B, Liao S, et al. Safety and pharmacokinetics of BMS-650032 following multiple ascending doses for 14 days in healthy subjects [abstract]. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC); 12-15 Sep 2010; Boston.
13. Lok AS, Gardiner D, Hezode C, Lawitz E, Bourliere M, Everson G, et al. Sustained virologic response in chronic HCV genotype (GT) 1-infected null responders with combination of daclatasvir (DCV; NS5A inhibitor) and asunaprevir (ASV; NS3 inhibitor) with or without peginterferon alfa-2a/ribavirin (PEG/RBV) [abstract no. 79]. Hepatology. 2012;56(Suppl 4):230A.
14. Charlton M. Telaprevir, boceprevir, cytochrome P450 and immunosuppressive agents - a potentially lethal cocktail. Hepatology. 2011;54(1):3-5.
15. Eley T, Gardiner D, Persson A, He B, You X, Shah V, et al. Evaluation of drug interaction potential of the HCV protease inhibitor asunaprevir (ASV; BMS-650032) at 200 mg twice daily (BID) in metabolic cocktail and P-glycoprotein (P-gp) probe studies in healthy volunteers [abstract]. Hepatology 2011;54(Suppl 1):381.
16. Bifano M, Sevinsky H, Stonier M, Jiang H, Bertz RJ. Daclatasvir, an HCV NS5A replication complex inhibitor, has minimal effect on pharmacokinetics of midazolam, a sensitive probe for cytochrome P450 3A4 [abstract no. O-15]. 8th International Workshop on Clinical Pharmacology of Hepatitis Therapy; 26-27 Jun 2013; Cambridge (MA).
17. BMS-790052 and BMS-650032: One-month Oral Combination Toxicity Study in Monkeys (DS08143). Bristol-Myers Squibb Research and Development, 2009. BMS Document Control No. 930035546.
18. Chan P, Tafoya E, Bifano M, Bertz R, Yin P, Hughes E, et al. Exposure-response analysis of daclatasvir in patients with genotype 1 chronic HCV infection: dose selection for phase 3 clinical trials [abstract no. PK-11]. Rev Antivir Ther Infect Dis. 2012;6:14.
19. Chan P, Tafoya E, Eley T, He B, Mendez P, Gardiner D, et al. Exposure-response analyses of asunaprevir in combination with daclatasvir +/- peginterferon/ribavirin among patients with genotype 1 chronic HCV infection: dose selection for phase 3 clinical trials. J Hepatol. 2013;58(Suppl 1):S328-9.
20. Lok AS, Gardiner DF, Lawitz E, Martorell C, Everson GT, Ghalib R, et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med. 2012;366(3):216-24.
21. Eley T, He B, Huang S, Li W, Pasquinelli C, Rodrigues AD, et al. Pharmacokinetics of the NS3 protease inhibitor, asunaprevir (ASV, BMS-650032), in phase I studies in subjects with or without chronic hepatitis C. Clin Pharm Drug Dev. 2013;2(4):316-27.
22. Bronowicki JP, Pol S, Thuluvath PJ, Larrey D, Martorell CT, Rustgi VK, 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.
23. Vertex Pharmaceuticals Inc. INCIVEK™ (telaprevir) prescribing information. 2013. http://pi.vrtx.com/files/uspi-telaprevir.pdf. Accessed 17 July 2014
24. Merck & Co., Inc. VICTRELIS™ (boceprevir) prescribing information. 2013. http://www.merck.com/product/usa/pi-circulars/v/victrelis/ victrelis-pi.pdf. Accessed 17 July 2014
25. Eley T, Chan P, Sverdlov O, He B, Bedford B, Kandoussi H, et al. Improved bioavailability and mitigated food effect for asunaprevir utilizing a lipid-based formulation: similar exposure with 100 mg twice daily softgel capsule relative to 200 mg twice daily of phase 2 tablet [abstract/poster no. A-1247]. 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 9-12 Sep 2012; San Francisco (CA).
26. Bronowicki JP, Pol S, Thuluvath PJ, Larrey D, Martorell CT, Rustgi VK, et al. Randomized study of asunaprevir plus peginterferon alfa and ribavirin for previously untreated genotype 1 chronic hepatitis C. Antivir Ther. 2013;18(7):885-93.
27. Benet LZ. Predicting drug disposition via application of a biopharmaceutics drug disposition classification system. Basic Clin Pharmacol Toxicol. 2010;106(3):162-7.
28. Eley T, Han YH, Huang SP, He B, Li W, Bedford B, et al. In vivo and in vitro assessment of asunaprevir (BMS-650032) as an inhibitor and substrate of organic anion polypeptide (OATP) transporters in healthy volunteers. International Workshop on Clinical Pharmacology of Hepatitis Therapy; 27-28 Jun 2012; Cambridge (MA).
29. Bifano M, Hwang C, Hartstra J, Tiessen RG. Assessment of HIV antiretroviral drug interactions with the HCV NS5A replication complex inhibitor daclatasvir demonstrates a PK profile which supports coadministration with tenofovir, efavirenz and atazanavir/r [poster no. 618]. 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012); 5-8 Mar 2012; Seattle (WA).
30. Bifano M, Sevinsky H, Persson A, Hwang C, Kandoussi H, Jiang H, et al. BMS-790052 has no effect on the pharmacokinetics of a combined oral contraceptive containing ethinyl estradiol and norgestimate in healthy female subjects [poster no. 1340]. The Liver Meeting 2011: The 62nd Annual Meeting of the American Association for the Study of Liver Diseases; 4-8 Nov 2011; San Francisco (CA).
31. Fontana RJ, Hughes EA, Appelman H, Hindes R, Dimitrova D, Bifano M. Case report of successful peginterferon, ribavirin, and daclatasvir therapy for recurrent cholestatic hepatitis C after liver retransplantation. Liver Transpl. 2012;18(9):1053-9.
32. Fontana RJ, Bifano M, Hindes R, Symonds WT, Dimitrova D. First ever successful use of daclatasvir and GS-7977, an interferon-free oral regimen, in a liver transplant recipient with severe recurrent hepatitis C [abstract]. Hepatology. 2012;56(Suppl 4):524A-5A.
33. Eley T, You X, Huang S, Symonds W, Li W, Sherman D, et al. Evaluation of drug interaction potential between daclatasvir and sofosbuvir. Rev Antivir Ther Infect Dis. 2013;6:16.
34. Bronowicki J, Pol S, Thuluvath P, Larrey D, Martorell CT, Rustgi VK, et al. Asunaprevir (ASV; BMS-650032), an NS3 protease inhibitor, in combination with peginterferon and ribavirin in treatment-naive patients with genotype 1 chronic hepatitis C infection [abstract no. 1096]. J Hepatol. 2012;56(Suppl 2):S431-2.
35. Hezode C, Hirschfield GM, Ghesquiere W, Sievert W, Rodriguez-Torres M, Shafran S, et al. Daclatasvir, an NS5A replication complex inhibitor, combined with peginterferon alfa-2a and ribavirin in treatment-naive HCV-genotype 1 or 4 subjects: phase 2b COMMAND-1 SVR12 results [abstract]. Hepatology. 2012;56(Suppl 4):553A-4A.
36. Chayama K, Takahashi S, Toyota J, Karino Y, Ikeda K, Ishikawa H, et al. Dual therapy with the nonstructural protein 5A inhibitor, daclatasvir, and the nonstructural protein 3 protease inhibitor, asunaprevir, in hepatitis C virus genotype 1b-infected null responders. Hepatology. 2012;55:742-8.
37. Lok A, Gardiner D, Hézode C, Lawitz E, Bourlière M, Everson G, et al. Confirmation that quadruple therapy with daclatasvir (NS5A inhibitor), asunaprevir (NS3 inhibitor) and peginterferon/ribavirin results in high rate of SVR4 in HCV genotype 1 null responders [abstract no. 1415]. J Hepatol 2012;56(Suppl 2):S557.
38. Pasquinelli C, McPhee F, Eley T, Villegas C, Sandy K, Wendelburg P, et al. Single and multiple ascending dose studies of the NS3 protease inhibitor asunaprevir in subjects with or without chronic hepatitis C. Antimicrob Agents Chemother. 2012;56:1838-44.