Use of modelling and simulation techniques to support decision making on the progression of PF-04878691, a TLR7 agonist being developed for hepatitis C

British Journal of Clinical Pharmacology

Volumn 73, Issue 1, 2012, Pages 77-92

  Jones, Hannah M ^a   Chan, Phylinda L S ^a   Van der Graaf, Piet H ^a   Webster, Robert ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

PKPD; Population modelling; TLR7

Indexed keywords

2',5' OLIGOADENYLATE SYNTHETASE; CPG 10101; PF 04878691; PLACEBO; TOLL LIKE RECEPTOR AGONIST; UNCLASSIFIED DRUG;

ABDOMINAL CRAMP; ADULT; ANTIVIRAL ACTIVITY; ARTICLE; BODYACHE; CHILL; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG FEVER; DRUG HALF LIFE; DRUG SAFETY; DRUG WITHDRAWAL; FATIGUE; FEMALE; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; HUMAN EXPERIMENT; HYPOTENSION; LOW BACK PAIN; LYMPHOCYTE; MALE; MAXIMUM PLASMA CONCENTRATION; NAUSEA; NORMAL HUMAN; PAIN; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SIMULATION;

2',5'-OLIGOADENYLATE SYNTHETASE; ADULT; COMPUTER SIMULATION; DECISION SUPPORT TECHNIQUES; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; FEMALE; HEPACIVIRUS; HEPATITIS C, CHRONIC; HUMANS; MALE; MIDDLE AGED; MODELS, BIOLOGICAL; RANDOMIZED CONTROLLED TRIALS AS TOPIC; TOLL-LIKE RECEPTOR 7; VIRAL LOAD; YOUNG ADULT;

EID: 83155176070     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/j.1365-2125.2011.04047.x     Document Type: Article

References (33)

1. Ghany MG, Strader DB, Thomas DL, Seeff LB. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009; 49: 1335-74.
2. Williams R. Global challenges in liver disease. Hepatology 2006; 44: 521-6.
3. Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med 2006; 144: 705-14.
4. Deuffic-Burban S, Poynard T, Sulkowski MS, Won JB. Estimating the future health burden of chronic hepatitis C and human immunodeficiency virus infections in the United States. J Viral Hepat 2007; 14: 107-15.
5. Shepherd J, Brodin H, Cave C, Waugh N, Price A, Gabbay J. Pegylated interferon alpha-2a and -2b in combination with ribavirin in the treatment of chronic hepatitis C: a systematic review and economic evaluation. Health Technol Assess 2004; 8: 1-125.
6. Medzhitov R, Janeway C Jr. Innate immunity. N Engl J Med 2000; 343: 338-44.
7. Biron CA. Interferons α and β as immune regulators - a new look. Immunity 2001; 14: 661-4.
8. Seki E, Brenner DA. Toll-like receptors and adapter molecules in liver disease: update. Hepatology 2008; 48: 322-35.
9. Fitzgerald-Bocarsly P, Dai J, Singh S. Plasmacytoid dendritic cells and type I IFN: 50 years of convergent history. Cytokine Growth Factor Rev 2008; 19: 3-19.
10. Schiller M, Metze D, Luger TA, Grabbe S, Gunzer M. Immune response modifiers - mode of action. Exp Dermatol 2006; 15: 331-41.
11. Edwards L, Ferenczy A, Eron L, Baker D, Owens ML, Fox TL, Hougham AJ, Schmitt KA, Self-administered topical 5% imiquimod cream for external anogenital warts. HPV Study Group. Human PapillomaVirus. Arch Dermatol 1998; 134: 25-30.
12. Goldstein D, Hertzog P, Tomkinson E, Couldwell D, McCarville S, Parrish S, Cunningham P, Newell M, Owens M, Cooper DA. Administration of imiquimod, an interferon inducer, in asymptomatic human immunodeficiency virus-infected persons to determine safety and biologic response modification. J Infect Dis 1998; 178: 858-61.
13. Horsmans Y, Berg T, Desager J, Mueller T, Schott E, Fletcher SP, Steffy KR, Bauman LA, Kerr BM, Averett DR. Isatoribine, an agonist of TLR7, reduces plasma virus concentration in chronic hepatitis C infection. Hepatology 2005; 42: 724-31.
14. Pockros PJ, Guyader D, Patton H, Tong MJ, Wright T, McHutchison JG, Meng TC. Oral resiquimod in chronic HCV infection: safety and efficacy of 2 placebo-controlled, double-blind phase IIa studies. J Hepatol 2007; 47: 174-82.
15. Dudek AZ, Yunis C, Harrison LI, Kumar S, Hawkinson R, Cooley S, Vasilakos JP, Gorski KS, Miller JS. First in human phase 1 trial of 852A, a novel systemic toll-like receptor 7 agonist, to activate innate immune responses in patients with advanced cancer. Clin Cancer Res 2007; 13: 7119-25.
16. McHutchison JG, Bacon BR, Gordon SC, Lawitz E, Shiffman M, Afdhal NH, Jacobson IM, Muir A, Al AM, Morris ML, Lekstrom HJA, Efler SM, Davis HL. Phase 1B, randomized, double-blind, dose-escalation trial of CPG 10101 in patients with chronic hepatitis C virus. Hepatology 2007; 46: 1341-9.
17. Harrison LI, Astry C, Kumar S, Yunis C. Pharmacokinetics of 852A, an imidazoquinoline Toll-like receptor 7-specific agonist, following intravenous, subcutaneous, and oral administrations in humans. J Clin Pharmacol 2007; 47: 962-9.
18. Thomas A, Laxton C, Rodman J, Myangar N, Horscroft N, Parkinson T. Investigating toll-like receptor agonists for potential to treat hepatitis C virus infection. Antimicrob Agents Chemother 2007; 51: 2969-78.
19. Fidock MD, Souberbielle BE, Laxton C, Rawal J, Delpuech-Adams O, Corey TP, Colman P, Kumar V, Cheng JB, Wright K, Srinivasan S, Rana K, Craig C, Horscroft N, Westby M, Webster R, van der Ryst E. The innate immune response, clinical outcomes and ex-vivo HCV antiviral efficacy of a TLR7 agonist (PF-4878691). Clin Pharmacol Ther 2011; 89: 821-9.
20. Beal SL, Sheiner LB, Boeckmann AJ. NONMEM Users Guides. Ellicott City, MD, USA: Icon Development Solutions, 19892006.
21. Jonkman JH, Nicholson KG, Farrow PR, Eckert M, Grasmeijer G, Oosterhuis B, De Noord OE, Guentert TW. Effects of alpha-interferon on theophylline pharmacokinetics and metabolism. Br J Clin Pharmacol 1989; 27: 795-802.
22. Leeson GA, Biedenbach SA, Chan KY, Gibson JP, Wright GJ. Decrease in the activity of the drug-metabolising enzymes of rat liver following the administration of tilorone hydrochloride. Drug Metab Dispos 1976; 4: 232-8.
23. Shiomi M, Funaki T. Pharmacokinetic/pharmacodynamic model analysis of pegylated interferon α-2a in healthy subjects. Jpn J Clin Pharmacol Ther 2003; 34: 177-85.
24. Motzer RJ, Rakhit A, Ginsberg M, Rittweger K, Vuky J, Yu R, Fettner S, Hooftman L. Phase I trial of 40-kd branched pegylated interferon alfa-2a for patients with advanced renal cell carcinoma. J Clin Oncol 2001; 19: 1312-9.
25. Di Bisceglie AM, Fan X, Chambers T, Strinko J. Pharmacokinetics, pharmacodynamics, and hepatitis C viral kinetics during antiviral therapy: the null responder. J Med Virol 2006; 78: 446-51.
26. Murashima S, Kumashiro R, Ide T, Miyajima I, Hino T, Koga Y, Ishii K, Ueno T, Sakisaka S, Sata M. Effect of interferon treatment on serum2′, 5′-oligoadenylate synthetase levels in hepatitis C-infected patients. J Med Virol 2000; 62: 185-90.
27. Wills RJ. Clinical pharmacokinetics of interferons. Clin Pharmacokinet 1990; 19: 390-9.
28. Lodemann E, Nitsche EM, Lang MH, Gerein V, Altmeyer P, Holzmann H, Kornhuber B. Serum interferon level and (2′-5′) oligoadenylate synthetase activity in lymphocytes during clinical interferon application. J Interferon Res 1985; 5: 621-8.
29. Luo S, Cassidy W, Jeffers L, Reddy KR, Bruno C, Howell CD. Interferon-stimulated gene expression in black and white hepatitis C patients during peginterferon alfa-2a combination therapy. Clin Gastroenterol Hepatol 2005; 3: 499-506.
30. Fried MW. Side effects of therapy of hepatitis C and their management. Hepatology 2002; 36: (Suppl. 1): S237-244.
31. Soza A, Everhart JE, Ghany MG, Doo E, Heller T, Promrat K, Park Y, Liang TJ, Hoofnagle JH. Neutropenia during combination therapy of interferon alfa and ribavirin for chronic hepatitis C. Hepatology 2002; 36: 1273-9.
32. Zucchini N, Bessou G, Traub S, Robbins SH, Uematsu S, Akira S, Alexopoulou L, Dalod M. Cutting edge: overlapping functions of TLR7 and TLR9 for innate defense against a herpesvirus infection. J Immunol 2008; 180: 5799-803.
33. Lagging M, Romero AI, Westin J, Norkrans G, Dhillon AP, Pawlotsky JM, Zeuzem S, von Wagner M, Negro F, Schalm SW, Haagmans BL, Ferrari C, Missale G, Neumann AU, Verheij-Hart E, Hellstrand K. IP-10 predicts viral response and therapeutic outcome in difficult-to-treat patients with HCV genotype 1 infection. Hepatology 2006; 44: 1617-25.