title: Clinical safety of the selective PKC-beta inhibitor, ruboxistaurin.
abstract: The aim of this manuscript is to report the safety profile of patients treated with ruboxistaurin mesylate (RBX; LY333531), a selective protein kinase C-beta (PKC-beta) inhibitor, for up to 4 years. Data from patients with diabetes (1396 RBX 32 mg/day; 1408 placebo) were combined from 11 placebo-controlled, double-masked studies. The proportion of patients who reported one or more serious adverse events was greater in the placebo group than in the RBX-treated group (23.2 versus 20.8%, respectively). There were 51 deaths (21 RBX; 30 placebo) reported in this patient cohort; none of the deaths was attributed to study drug by the investigators. Common adverse drug reactions (> or = 1/100 - < 1/10 patients) that were reported in the RBX-treated patients were dyspepsia and increased blood creatine phosphokinase. In controlled, randomised clinical trials, RBX had an adverse event profile comparable to placebo, and was well tolerated.
authors.affiliation: Washington University School of Medicine, 660 S. Euclid, Campus Box 8127, St. Louis, MO 63110, USA. jmcgill@im.wustl.edu
authors.forename: Janet B
authors.initials: JB
authors.lastname: McGill
authors.forename: George L
authors.initials: GL
authors.lastname: King
authors.forename: Paul H
authors.initials: PH
authors.lastname: Berg
authors.forename: Karen L
authors.initials: KL
authors.lastname: Price
authors.forename: Keri A
authors.initials: KA
authors.lastname: Kles
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Bastyr
authors.forename: David L
authors.initials: DL
authors.lastname: Hyslop
mesh_terms: D006801:Humans; D007211:Indoles / Q000009:adverse effects*; D008301:Maleimides / Q000009:adverse effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D064546:Protein Kinase C beta; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic / Q000639:trends*
chemical_list: D007211:Indoles; D008301:Maleimides; D047428:Protein Kinase Inhibitors; C099154:ruboxistaurin; D011493:Protein Kinase C; D064546:Protein Kinase C beta