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Sotrastaurin, a novel small molecule inhibiting protein-kinase C: Randomized phase II study in renal transplant recipients

par Friman, Styrbjorn;Arns, Wolfgang;Nashan, Björn;Vincenti, Flavio;Banas, Bernhard;Budde, Klemens;Cibrik, Diane;Chan, Lingtakneander;Klempnauer, Jürgen;Mulgaonkar, Shamkant;Nicholson, Michael;Wahlberg, Jan;Wissing, Karl Martin ;Abrams, Ken;Witte, Steffen;Woodle, Ervin Steve
Référence American Journal of Transplantation, 11, 7, page (1444-1455)
Publication Publié, 2011-07

Article révisé par les pairs

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Résumé :

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. © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.