The safety profile of eltrombopag, a novel oral platelet growth factor, in thrombocytopenic patients and healthy subjects

Abstract

18596 Background: Eltrombopag (SB-497115) is an oral, non-peptide, small molecule, thrombopoietin receptor agonist being tested as a potential treatment for thrombocytopenia. Eltrombopag has been shown to increase platelet counts in both healthy subjects and thrombocytopenic patients. Methods: Safety and tolerability data for eltrombopag (3–75 mg for up to 6 weeks) is presented from randomized, placebo-controlled, parallel group clinical trials involving 115 healthy subjects and 104 immune thrombocytopenic purpura (ITP) patients. Safety and tolerability endpoints involved assessment of adverse events (AE) and clinical laboratory parameters, including ECGs and platelet function. Results: In 3 Phase I trials, 98 healthy males received active eltrombopag QD for up to 10 days at 3–75 mg. In the Phase II dose ranging study, 78 chronic ITP patients (28 male/50 female) received active eltrombopag QD for 6 weeks at doses of 30–75 mg. There was no apparent relationship between active and control arms, the dose of eltrombopag and the incidence or severity of AEs, changes in laboratory values, platelet function or cardiac parameters in any of the studies. There were no serious adverse events (SAEs) reported by subjects in the 3 Phase I studies. 5 SAEs were reported in 1 patient in the ITP study that were considered by the investigator as possibly associated with administration of 50 mg eltrombopag. No SAEs were related to 30 mg or 75 mg eltrombopag, and 2 SAEs in 2 patients were related to placebo. Conclusions: There was no apparent relationship between eltrombopag dose and safety endpoints in these studies. These encouraging safety and tolerability data support the further testing of eltrombopag in phase II and III studies involving patients with ITP and chronic liver disease, and cancer patients receiving thrombocytopenic chemotherapy. [Table: see text]