Phase 1 dose-escalation study of CP-690 550 in stable renal allograft recipients: Preliminary findings of safety, tolerability, effects on lymphocyte subsets and pharmacokinetics
CP-690 550 inhibits Janus kinase 3 with nanomolar potency. In this dose-escalation study, we assessed the safety, tolerability, effects on lymphocyte subsets, and pharmacokinetics of CP-690 550 when coadministered with mycophenolate mofetil in stable renal allograft recipients for 28 days. Twenty-eight patients were enrolled. Six patients received CP-690 550 5 mg twice daily (BID), 6 patients received 15 mg BID, 10 patients received 30 mg BID, and 6 patients received placebo. The most frequent adverse events were infections and gastrointestinal (abdominal pain, diarrhea, dyspepsia, and vomiting). CP-690 550 15 mg BID and 30 mg BID were associated with a mean decrease in hemoglobin from baseline of 11% and a mean decrease in absolute natural killer cell counts of 50%. CP-690 550 30 mg BID was also associated with a mean increase in absolute CD19+B-lymphocytes of 130%. There were no changes in the number of neutrophils, total lymphocytes, platelets, or CD4+or CD8+T cells; clinical chemistry; vital signs; or electrocardiograms from the pretreatment baseline. Administration of CP-690 550 without a concomitant calcineurin inhibitor resulted in CP-690 550 exposures consistent with previous studies in nontransplant subjects. Additional dose-ranging studies are warranted to evaluate the safety and efficacy of CP-690 550 in renal transplant recipients over longer treatment duration.
|Keywords||Pharmacotherapy, Renal transplant recipients, Transplant rejection|
|Persistent URL||dx.doi.org/10.1111/j.1600-6143.2008.02307.x, hdl.handle.net/1765/30487|
van Gurp, E., Weimar, W., Gaston, R., Brennan, D., Mendez, R., Pirsch, J., … Chow, V.. (2008). Phase 1 dose-escalation study of CP-690 550 in stable renal allograft recipients: Preliminary findings of safety, tolerability, effects on lymphocyte subsets and pharmacokinetics. American Journal of Transplantation, 8(8), 1711–1718. doi:10.1111/j.1600-6143.2008.02307.x