The Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a TYK2/JAK1 Inhibitor (PF-06700841) in Healthy Subjects and Patients With Plaque Psoriasis

Journal of Clinical Pharmacology

Volumn 58, Issue 4, 2018, Pages 434-447

  Banfield, Christopher ^a   Scaramozza, Matthew ^a   Zhang, Weidong ^a   Kieras, Elizabeth ^a   Page, Karen M ^a   Fensome, Andrew ^a   Vincent, Michael ^a   Dowty, Martin E ^a   Goteti, Kosalaram ^a   Winkle, Peter J ^b   Peeva, Elena ^a  

^a PFIZER INC   (United States)

^b Anaheim Clinical Trials   (United States)

Author keywords

inflammation; Janus kinase 1 (JAK1) inhibitor; pharmacokinetics and drug metabolism; plaque psoriasis; tyrosine kinase 2 (TYK2)

Indexed keywords

ANTIPSORIASIS AGENT; BIOLOGICAL MARKER; C REACTIVE PROTEIN; CREATININE; CYSTATIN C; GAMMA INTERFERON INDUCIBLE PROTEIN 10; HEMOGLOBIN; JANUS KINASE 1; PF 06700841; PROTEIN KINASE TYK2; PROTEIN TYROSINE KINASE INHIBITOR; UNCLASSIFIED DRUG; JAK1 PROTEIN, HUMAN; PROTEIN KINASE INHIBITOR; TYK2 PROTEIN, HUMAN;

ACCUMULATION RATIO; ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; B LYMPHOCYTE; CD3+ T LYMPHOCYTE; COHORT ANALYSIS; CONCENTRATION AT STEADY-STATE; CONTROLLED STUDY; CREATININE BLOOD LEVEL; CREATININE CLEARANCE; CYTOTOXIC T LYMPHOCYTE; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG EXPOSURE; DRUG HALF LIFE; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ELIMINATION HALF-LIFE; ESTIMATED GLOMERULAR FILTRATION RATE; FEMALE; HELPER CELL; HEMOGLOBIN BLOOD LEVEL; HUMAN; LIMIT OF QUANTITATION; LYMPHOCYTE COUNT; MAJOR CLINICAL STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; MULTIPLE DRUG DOSE; NATURAL KILLER CELL; NEUTROPENIA; NEUTROPHIL COUNT; PARALLEL DESIGN; PEAK-TROUGH FLUCTUATION; PHARMACODYNAMIC PARAMETERS; PHARMACOKINETIC PARAMETERS; PHASE 1 CLINICAL TRIAL; PLASMA CONCENTRATION-TIME CURVE; PLATELET COUNT; PSORIASIS AREA AND SEVERITY INDEX; PSORIASIS VULGARIS; RANDOMIZED CONTROLLED TRIAL; RENAL CLEARANCE; RETICULOCYTE COUNT; SIDE EFFECT; SINGLE DRUG DOSE; TABLET FORMULATION; TIME TO MAXIMUM PLASMA CONCENTRATION; VOLUME OF DISTRIBUTION; ADOLESCENT; ANTAGONISTS AND INHIBITORS; BIOAVAILABILITY; BLOOD; BLOOD CELL COUNT; CLINICAL TRIAL; MIDDLE AGED; NORMAL HUMAN; PSORIASIS; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; BIOLOGICAL AVAILABILITY; BLOOD CELL COUNT; C-REACTIVE PROTEIN; DOUBLE-BLIND METHOD; FEMALE; HEALTHY VOLUNTEERS; HUMANS; JANUS KINASE 1; MALE; MIDDLE AGED; PROTEIN KINASE INHIBITORS; PSORIASIS; TYK2 KINASE; YOUNG ADULT;

EID: 85038608102     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1002/jcph.1046     Document Type: Article

References (33)

1. O'Shea JJ, Kontzias A, Yamaoka K, Tanaka Y, Laurence A. Janus kinase inhibitors in autoimmune diseases. Ann Rheum Dis. 2013;72(Suppl 2):ii111–ii115.
2. Colamonici O, Yan H, Domanski P, et al. Direct binding to and tyrosine phosphorylation of the alpha subunit of the type I interferon receptor by p135tyk2 tyrosine kinase. Mol Cell Biol. 1994;14(12):8133–8142.
3. Novick D, Cohen B, Rubinstein M. The human interferon alpha/beta receptor: characterization and molecular cloning. Cell. 1994;77(3):391–400.
4. Abramovich C, Shulman LM, Ratovitski E, et al. Differential tyrosine phosphorylation of the IFNAR chain of the type I interferon receptor and of an associated surface protein in response to IFN-alpha and IFN-beta. EMBO J. 1994;13(24):5871–5877.
5. Finbloom DS, Winestock KD. IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes. J Immunol. 1995;155(3):1079–1090.
6. Rodríguez-Liñares B, Watson SP. Thrombopoietin potentiates activation of human platelets in association with JAK2 and TYK2 phosphorylation. Biochem J. 1996;316(Pt 1):93–98.
7. Asao H, Okuyama C, Kumaki S, et al. Cutting edge: the common gamma-chain is an indispensable subunit of the IL-21 receptor complex. J Immunol. 2001;167(1):1–5.
8. O'Sullivan LA, Liongue C, Lewis RS, Stephenson SE, Ward AC. Cytokine receptor signaling through the Jak-Stat-Socs pathway in disease. Mol Immunol. 2007;44(10):2497–2506.
9. Ghoreschi K, Laurence A, O'Shea JJ. Janus kinases in immune cell signaling. Immunol Rev. 2009;228(1):273–287.
10. Teng MW, Bowman EP, McElwee JJ, et al. IL-12 and IL-23 cytokines: from discovery to targeted therapies for immune-mediated inflammatory diseases. Nat Med. 2015;21(7):719–729.
11. Namour F, Diderichsen PM, Cox E, et al. Pharmacokinetics and pharmacokinetic/pharmacodynamic modeling of filgotinib (GLPG0634), a selective JAK1 inhibitor, in support of phase IIB dose selection. Clin Pharmacokinet. 2015;54(8):859–874.
12. Bissonnette R, Luchi M, Fidelus-Gort R, et al. A randomized, double-blind, placebo-controlled, dose-escalation study of the safety and efficacy of INCB039110, an oral janus kinase 1 inhibitor, in patients with stable, chronic plaque psoriasis. J Dermatolog Treat. 2016;27(4):332–338.
13. Ludbrook VJ, Hicks KJ, Hanrott KE, et al. Investigation of selective JAK1 inhibitor GSK2586184 for the treatment of psoriasis in a randomized placebo-controlled phase IIa study. Br J Dermatol. 2016;174(5):985–995.
14. Kremer JM, Emery P, Camp HS, et al. A phase IIb study of ABT-494, a selective JAK-1 inhibitor, in patients with rheumatoid arthritis and an inadequate response to anti-tumor necrosis factor therapy. Arthritis Rheumatol. 2016;68(12):2867–2877.
15. Kontzias A, Kotlyar A, Laurence A, Changelian P, O'Shea JJ. Jakinibs: a new class of kinase inhibitors in cancer and autoimmune disease. Curr Opin Pharmacol. 2012;12(4):464–470.
16. Norman P. Selective JAK inhibitors in development for rheumatoid arthritis. Expert Opin Investig Drugs. 2014;23(8):1067–1077.
17. Strober B, Sigurgeirsson B, Popp G, et al. Secukinumab improves patient-reported psoriasis symptoms of itching, pain, and scaling: results of two phase 3, randomized, placebo-controlled clinical trials. Int J Dermatol. 2016;55(4):401–407.
18. Gordon KB, Colombel JF, Hardin DS. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016;375(21):2102.
19. Griffiths CE, Reich K, Lebwohl M, et al. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet. 2015;386(9993):541–551.
20. Papp KA, Langley RG, Lebwohl M, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 2008;371(9625):1675–1684.
21. Louden BA, Pearce DJ, Lang W, Feldman SR. A Simplified Psoriasis Area Severity Index (SPASI) for rating psoriasis severity in clinic patients. Dermatol Online J. 2004;10(2):7.
22. Hsu L, Armstrong AW. JAK inhibitors: treatment efficacy and safety profile in patients with psoriasis. J Immunol Res. 2014;2014:283617.
23. Tan H, Valdez H, Griffiths CE, et al. Early clinical response to tofacitinib treatment as a predictor of subsequent efficacy: results from two phase 3 studies of patients with moderate-to-severe plaque psoriasis. J Dermatolog Treat. 2017;28(1):3–7.
24. Ishizaki M, Muromoto R, Akimoto T, et al. Tyk2 is a therapeutic target for psoriasis-like skin inflammation. Int Immunol. 2014;26(5):257–267.
25. Pfizer, data on file: In vitro evaluation of PF-067800841 as an inhibitor of MDR1, OATP1B1, OATP1B3, OCT2, MATE1, and MATE2K transporters 2015:1–18.
26. Zhu Y, Ye X, Zhu B, et al. Comparisons between the 2012 new CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations and other four approved equations. PLoS One. 2014;9(1):e84688.
27. Kaupke CJ, Butler GC, Vaziri ND. Effect of recombinant human erythropoietin on platelet production in dialysis patients. J Am Soc Nephrol. 1993;3(10):1672–1679.
28. Kremer JM, Cohen S, Wilkinson BE, et al. A phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone. Arthritis Rheum. 2012;64(4):970–981.
29. Isaacs JD, Zuckerman A, Krishnaswami S, et al. Changes in serum creatinine in patients with active rheumatoid arthritis treated with tofacitinib: results from clinical trials. Arthritis Res Ther. 2014;16(4):R158.
30. Strober B, Buonanno M, Clark JD, et al. Effect of tofacitinib, a Janus kinase inhibitor, on haematological parameters during 12 weeks of psoriasis treatment. Br J Dermatol. 2013;169(5):992–999.
31. Nishimoto N, Yoshizaki K, Miyasaka N, et al. Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum. 2004;50(6):1761–1769.
32. Maini RN, Taylor PC, Szechinski J, et al. Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum. 2006;54(9):2817–2829.
33. Smolen JS, Beaulieu A, Rubbert-Roth A, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008;371(9617):987–997.