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The safety and metabolic effects of high-dose immunosuppression were determined, followed by autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) in newly diagnosed type 1 diabetes mellitus (DM). With AHST, beta cell function was found to be increased in all but 1 patient and induced prolonged insulin independence in the majority of the patients.

A novel bioequivalence testing approach was used to determine intrasubject variability and switchability of two ciclosporin formulations, SangCya[sup TM] (test) and Neoral[sup ®] (reference). Twenty healthy volunteers were enrolled into a single-dose, randomized, open-label, 4-period, 2-sequence study with a crossover replicate design. Subject-by-formulation interaction variances were compared using a mixed effects linear model. Intrasubject variability for ln AUC[sub 0–∞] and ln C[sub max] of SangCya and Neoral were not significantly different. The 95% confidence intervals of the intrasubject variability of AUC[sub 0–∞] (0.94) and C[sub max] (1.28) as determined using the bootstrap nonparametric percentile method (n = 2,000) were below the individual bioequivalence limit estimated at 2.25. We concluded equivalent intrasubject variability of ciclosporin pharmacokinetics and switchability between SangCya and Neoral. [ABSTRACT FROM AUTHOR]

Introduction: Recombinant P-selectin glycoprotein ligand IgG fusion protein, rPSGL-Ig (YSPSL), a fusion protein of human P-selectin ligand and IgG1-Fc, blocks leukocyte adhesion and protects against ischemia reperfusion injury (IRI) in animal models., Patients and Methods: This randomized 15-center, double-blind, 59-patient Ph2a study assessed YSPSL's safety in recipients of deceased-donor kidney allografts and its potential efficacy in improving early graft function. Two doses and two dosing modalities were evaluated., Results: No drug-specific toxicities or increased adverse event rates were noted. Two YSPSL-treated patients died of causes determined as unrelated to study drug. YSPSL did not reduce the incidence of dialysis within the first week post-transplant (41% in treated vs. 20% in placebo patients). Renal function endpoints scored at post-operative days 1 & 2 were also not impacted by YSPSL. However, at day 5, the fraction of patients with serum creatinine above 6 mg/dL was lower in the YSPSL vs. placebo group (26% vs. 55%, p = 0.043). Large variations in the dialysis-delayed graft function (DGF) rates were observed between centers, independently of treatment assignment, indicating subjectivity of this endpoint., Conclusion: In this first Ph2a study in kidney transplantation, YSPSL was safe but did not impact the dialysis-DGF rate. Further studies with more objective efficacy endpoints are required to define the impact of YSPSL on early renal allograft function., (© 2010 John Wiley & Sons A/S.)