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

E. Van Gurp, W. Weimar, R. Gaston, D. Brennan, R. Mendez, J. Pirsch, S. Swan, M. D. Pescovitz, G. Ni, C. Wang, S. Krishnaswami, V. Chow, G. Chan

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)1711-1718
Number of pages8
JournalAmerican Journal of Transplantation
Volume8
Issue number8
DOIs
StatePublished - Aug 1 2008
Externally publishedYes

Keywords

  • Pharmacotherapy
  • Renal transplant recipients
  • Transplant rejection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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