Friman, S. and Arns, W. and Nashan, B. and Vincenti, F. and Banas, B. and Budde, K. and Cibrik, D. and Chan, L. and Klempnauer, J. and Mulgaonkar, S. and Nicholson, M. and Wahlberg, J. and Wissing, K. -M. and Abrams, K. and Witte, S. and Woodle, E. S. (2011) Sotrastaurin, a Novel Small Molecule Inhibiting Protein-Kinase C: Randomized Phase II Study in Renal Transplant Recipients. AMERICAN JOURNAL OF TRANSPLANTATION, 11 (7). pp. 1444-1455. ISSN 1600-6135,
Full text not available from this repository. (Request a copy)Abstract
Sotrastaurin, a selective protein-kinase-C inhibitor, blocks early T-cell activation through a calcineurin-independent mechanism. In this study, de novo renal transplant recipients with immediate graft function were randomized 1: 2 to tacrolimus (control, n = 44) or sotrastaurin (300 mg b.i.d.; n = 81). All patients received basiliximab, mycophenolic acid (MPA) and steroids. The primary endpoint was the composite of treated biopsy-proven acute rejection (BPAR), graft loss, death or lost to follow-up at month 3. The main safety assessment was estimated glomerular filtration rate (eGFR); modification of diet in renal disease (MDRD) at month 3. Composite efficacy failure at month 3 was higher for the sotrastaurin versus control regimen (25.7% vs. 4.5%, p = 0.001), driven by higher BPAR rates (23.6% vs. 4.5%, p = 0.003), which led to early study termination. Median (+/- standard deviation [SD]) eGFR was higher for sotrastaurin versus control at all timepoints from day 7 (month 3: 59.0 +/- 22.3 vs. 49.5 +/- 17.7 mL/min/1.73 m(2), p = 0.006). The most common adverse events were gastrointestinal disorders (control: 63.6%; sotrastaurin: 88.9%) which led to study-medication discontinuation in two sotrastaurin patients. This study demonstrated a lower degree of efficacy but better renal function with the calcineurin-inhibitor-free regimen of sotrastaurin+MPA versus the tacrolimus-based control. Ongoing studies are evaluating alternative sotrastaurin regimens.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MYCOPHENOLATE-MOFETIL; CALCINEURIN INHIBITORS; CYCLOSPORINE; REJECTION; PSORIASIS; TRIAL; Allotransplantation; calcineurin inhibitor toxicity; drug development; efficacy; immunosuppression; mycophenolic acid; renal function; safety; tacrolimus; T-cell activation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Jun 2020 11:38 |
| Last Modified: | 08 Jun 2020 11:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20607 |
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