Pharmacokinetics, Safety and Tolerability of ABT-494, a Novel Selective JAK 1 Inhibitor, in Healthy Volunteers and Subjects with Rheumatoid Arthritis

Clinical Pharmacokinetics

Volumn 55, Issue 12, 2016, Pages 1547-1558

  Mohamed, Mohamed Eslam F ^a   Camp, Heidi S ^a   Jiang, Ping ^a   Padley, Robert J ^a   Asatryan, Armen ^a   Othman, Ahmed A ^a,b  

^a ABBVIE INC   (United States)

^b CAIRO UNIVERSITY   (Egypt)

Author keywords

[No Author keywords available]

Indexed keywords

METHOTREXATE; PLACEBO; UPADACITINIB; ABT-494; ANTIRHEUMATIC AGENT; FUSED HETEROCYCLIC RINGS; JANUS KINASE 1;

ABDOMINAL DISCOMFORT; ABDOMINAL PAIN; ACCUMULATION INDEX; ADULT; ARTICLE; BACKACHE; BODY MASS; CLINICAL ARTICLE; CONTROLLED STUDY; DIARRHEA; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG FORMULATION; DRUG SAFETY; DRUG TOLERABILITY; DRUG URINE LEVEL; ELIMINATION HALF-LIFE; ELIMINATION RATE CONSTANT; EVENING DOSAGE; FEMALE; HEADACHE; HUMAN; INSOMNIA; LIMIT OF QUANTITATION; LIQUID CHROMATOGRAPHY; MALE; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MEAN RESIDENCE TIME; MINIMUM PLASMA CONCENTRATION; MORNING DOSAGE; MULTIPLE CYCLE TREATMENT; MULTIPLE DRUG DOSE; NAUSEA; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PRESYNCOPE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RENAL CLEARANCE; RHEUMATOID ARTHRITIS; RHINOPHARYNGITIS; SINGLE DRUG DOSE; TREATMENT DURATION; UPPER RESPIRATORY TRACT INFECTION; URINARY EXCRETION; VIRAL GASTROENTERITIS; VOMITING; ADOLESCENT; AGED; ANTAGONISTS AND INHIBITORS; AREA UNDER THE CURVE; ARTHRITIS, RHEUMATOID; CLINICAL TRIAL; DRUG ADMINISTRATION; HALF LIFE TIME; METABOLIC CLEARANCE RATE; MIDDLE AGED; NORMAL HUMAN; ORAL DRUG ADMINISTRATION; YOUNG ADULT;

ADMINISTRATION, ORAL; ADOLESCENT; ADULT; AGED; ANTIRHEUMATIC AGENTS; AREA UNDER CURVE; ARTHRITIS, RHEUMATOID; DRUG ADMINISTRATION SCHEDULE; FEMALE; HALF-LIFE; HEALTHY VOLUNTEERS; HETEROCYCLIC COMPOUNDS, 3-RING; HUMANS; JANUS KINASE 1; MALE; METABOLIC CLEARANCE RATE; MIDDLE AGED; YOUNG ADULT;

EID: 84994894862     PISSN: 03125963     EISSN: 11791926     Source Type: Journal    
DOI: 10.1007/s40262-016-0419-y     Document Type: Article

References (29)

1. Wilkie WS, Schwieterman P. Strategies for the management of rheumatoid arthritis. Orthopedics. 2012;35(2):125–30.
2. Rindfleisch JA, Muller D. Diagnosis and management of rheumatoid arthritis. Am Fam Phys. 2005;72(6):1037–47.
3. Leonard WJ. Role of Jak kinases and STATs in cytokine signal transduction. Int J Hematol. 2001;73(3):271–7.
4. O’Shea JJ, Plenge R. JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity. 2012;36(4):542–50.
5. Vaddi K, Luchi M. JAK inhibition for the treatment of rheumatoid arthritis: a new era in oral DMARD therapy. Expert Opin Investig Drugs. 2012;21(7):961–73.
6. Isomaki P, Junttila I, Vidqvist KL, Korpela M, Silvennoinen O. The activity of JAK-STAT pathways in rheumatoid arthritis: constitutive activation of STAT3 correlates with interleukin 6 levels. Rheumatol (Oxf). 2015;54(6):1103–13.
7. He Y, Wong AY, Chan EW, Lau WC, Man KK, Chui CS, et al. Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: a systematic review and meta-analysis. BMC Musculoskelet Disord. 2013;14:298.
8. Zerbini CA, Lomonte AB. Tofacitinib for the treatment of rheumatoid arthritis. Expert Rev Clin Immunol. 2012;8(4):319–31.
9. 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):464–70.
10. Neubauer H, Cumano A, Muller M, Wu H, Huffstadt U, Pfeffer K. Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis. Cell. 1998;93(3):397–409.
11. Norman P. Selective JAK inhibitors in development for rheumatoid arthritis. Expert Opin Investig Drugs. 2014;23(8):1067–77.
12. Voss J, Graff C, Schwartz A, Hyland D, Argiriadi M, Camp H, et al. Pharmacodynamics of a novel Jak1 selective inhibitor in rat arthritis and anemia models and in healthy human subjects. Arthritis Rheum. 2013;65(10):1.
13. Kremer JM, Keystone EC, Emery P, Camp HS, Friedman A, Wang L, et al. Safety and efficacy of ABT-494, a novel selective JAK1 inhibitor, in patients with active rheumatoid arthritis and inadequate response or intolerance to anti-TNF biologic therapy. Arthritis Rheumatol. 2015;67(Suppl):10.
14. AbbVie. A study investigating the efficacy and safety of ABT-494 given with methotrexate (MTX) in subjects with rheumatoid arthritis who have had an inadequate response to MTX alone [ClinicalTrials.gov identifier NCT02066389]. US National Institutes of Health, ClinicalTrials.gov. Available at: http://www.clinicaltrials.gov. Accessed 22 Apr 2016.
15. AbbVie. A multicenter, randomized, double-blind, placebo-controlled study of ABT-494 for the induction of symptomatic and endoscopic remission in subjects with moderately to severely active Crohn’s disease who have inadequately responded to or are intolerant to anti-TNF therapy (Celest Study) [ClinicalTrials.gov identifier NCT02365649]. US National Institutes of Health, ClinicalTrials.gov. Available at: http://www.clinicaltrials.gov. Accessed 22 Apr 2016.
16. AbbVie. A study comparing ABT-494 to placebo and to adalimumab in subjects with rheumatoid arthritis who are on a stable dose of methotrexate and who have an inadequate response to methotrexate (SELECT-COMPARE) [ClinicalTrials.gov identifier NCT02629159]. US National Institutes of Health, ClinicalTrials.gov. Available at: http://www.clinicaltrials.gov. Accessed 22 Apr 2016.
17. AbbVie. A study comparing ABT-494 monotherapy to methotrexate (MTX) monotherapy in subjects with rheumatoid arthritis (RA) who have an inadequate response to MTX (SELECT-MONOTHERAPY) [ClinicalTrials.gov identifier NCT02706951]. US National Institutes of Health, ClinicalTrials.gov. Available at: http://www.clinicaltrials.gov. Accessed 22 Apr 2016.
18. AbbVie. A study to compare ABT-494 to placebo in subjects with rheumatoid arthritis on stable dose of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) who have an inadequate response or intolerance to biologic DMARDs (SELECT-BEYOND) [ClinicalTrials.gov identifier NCT02706847]. US National Institutes of Health, ClinicalTrials.gov. Available at: http://www.clinicaltrials.gov. Accessed 22 Apr 2016.
19. AbbVie. A study in healthy adults and adult subjects with rheumatoid arthritis to evaluate the safety, tolerability and pharmacokinetics after multiple doses of ABT-494 [ClinicalTrials.gov identifier NCT01741493]. US National Institutes of Health, ClinicalTrials.gov. Available at: http://www.clinicaltrials.gov. Accessed 22 Apr 2016.
20. Dutta S, Reed RC. Functional half-life is a meaningful descriptor of steady-state pharmacokinetics of an extended-release formulation of a rapidly cleared drug: as shown by once-daily divalproex-ER. Clin Drug Investig. 2006;26(12):681–90.
21. FDA. Guidance for industry. Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials. 2007. Available at: http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Vaccines/ucm074775.htm.
22. Sahin S, Benet LZ. The operational multiple dosing half-life: a key to defining drug accumulation in patients and to designing extended release dosage forms. Pharm Res. 2008;25(12):2869–77.
23. FDA, Center for Drug Evaluation and Research. Clinical pharmacology and biopharmaceutics review(s): tofacitinib. Application number 203214Orig1s000. 2011. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203214Orig1s000ClinPharmR.pdf.
24. Namour F, Diderichsen PM, Cox E, Vayssiere B, Van der Aa A, Tasset C, 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):859–74.
25. Mangoni AA, Jackson SH. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol. 2004;57(1):6–14.
26. Ma MH, Kingsley GH, Scott DL. A systematic comparison of combination DMARD therapy and tumour necrosis inhibitor therapy with methotrexate in patients with early rheumatoid arthritis. Rheumatol (Oxf). 2010;49(1):91–8.
27. Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012;64(5):625–39.
28. Smolen JS, Landewe R, Breedveld FC, Buch M, Burmester G, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73(3):492–509.
29. Dervieux T, Furst D, Lein DO, Capps R, Smith K, Walsh M, et al. Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis. Arthritis Rheum. 2004;50(9):2766–74.