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Sotrastaurin, a Novel Small Molecule Inhibiting Protein‐Kinase C: Randomized Phase II Study in Renal Transplant Recipients
Author(s) -
Friman S.,
Arns W.,
Nashan B.,
Vincenti F.,
Banas B.,
Budde K.,
Cibrik D.,
Chan L.,
Klempnauer J.,
Mulgaonkar S.,
Nicholson M.,
Wahlberg J.,
Wissing K.M.,
Abrams K.,
Witte S.,
Woodle E. S.
Publication year - 2011
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2011.03538.x
Subject(s) - medicine , renal function , calcineurin , basiliximab , mycophenolic acid , urology , regimen , adverse effect , discontinuation , tacrolimus , transplantation , gastroenterology
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 .