title: A supratherapeutic dose of the Janus kinase inhibitor tasocitinib (CP-690,550) does not prolong QTc interval in healthy participants.
abstract: Tasocitinib (CP-690,550), a selective inhibitor of the Janus kinase (JAK) family, is being developed for the treatment of several autoimmune diseases and prevention of allograft rejection. The aim of this study was to characterize the effect of tasocitinib on QT interval. Sixty male and female healthy adults were enrolled in a single-dose, randomized, 3-period, crossover study of a supratherapeutic dose of tasocitinib (100 mg), placebo, and moxifloxacin 400 mg. Triplicate electrocardiograms were performed at predose baseline and serially over 24 hours postdose in each treatment period. The upper limits of the 2-sided 90% confidence intervals (CIs) for the difference in QTc interval, corrected using Fridericia correction (QTcF), between tasocitinib and placebo were less than 5 ms at all time points. Concentration-QTcF analysis showed that the predicted mean change (90% CI) in QTcF at the observed mean C(max) was -0.12 (-1.18, 0.94) ms. For moxifloxacin, mean (90% CI) estimates of the change in QTcF from placebo were 11.3 (9.4, 13.1) and 12.5 (10.7, 14.4) ms at 2 and 4 hours, respectively, thereby establishing study sensitivity. A single supratherapeutic dose of tasocitinib 100 mg was well tolerated and not associated with QTc prolongation.
authors.affiliation: Pfizer, Inc, 50 Pequot Avenue, New London, CT 06320, USA. Sriram.krishnaswami@pfizer.com
authors.forename: Sriram
authors.initials: S
authors.lastname: Krishnaswami
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kudlacz
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Gary
authors.initials: G
authors.lastname: Chan
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008133:Long QT Syndrome / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010880:Piperidines; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D013599:Systole / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; C507933:JAK3 protein, human; D053616:Janus Kinase 3