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

EAFJ (Eveline) van Gurp, Willem Weimar, R Gaston, D Brennan, Alejandra Mendez Romero, J Pirsch, S Swan, MD Pescovitz, G Ni, C Wang, S Krishnaswami, V Chow, G Chan

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Abstract

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.
Original languageUndefined/Unknown
Pages (from-to)1711-1718
Number of pages8
JournalAmerican Journal of Transplantation
Volume8
Issue number8
DOIs
Publication statusPublished - 2008

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