Safety of Eltrombopag, an Oral Non-Peptide Platelet Growth Factor, in the Treatment of Thrombocytopenia: Results of Four Randomized, Placebo-Controlled Studies
Authors: Bussel James B. , McHutchison John , Provan Drew , Jagiello-Gruzfeld A. , Rafi Rezvan , Goodison Sophia 
Published: October 2019

Abstract
Eltrombopag is an oral, non-peptide, platelet growth factor that increases platelet counts in a dose-dependent manner in adult subjects with chronic idiopathic thrombocytopenic purpura (ITP) and Hepatitis C virus (HCV)-associated thrombocytopenia. Safety results from four completed randomized, double-blind, placebo-controlled studies are presented here. In two 6-week studies of subjects with ITP, 231 subjects were analyzed for safety following administration of eltrombopag once daily. In the first study, 117 patients were randomized to eltrombopag 30 mg, 50 mg or 75 mg or placebo. In the second study, 114 patients were administered 50 mg eltrombopag with increases to 75 mg after 3 weeks, if necessary. In the third study, which investigated the effect of eltrombpag 50 mg, 75 mg or 100 mg in subjects with chemotherapy-induced thrombocytopenia (CIT), 180 subjects were included in the safety analysis; subjects were administered up to 8 cycles of carboplatin/paclitaxel plus once daily eltrombopag for 10 days per cycle. In a fourth study, 74 subjects with HCV-associated thrombocytopenia were analyzed for safety; eltrombopag was administered once-dailyat doses of 30 mg, 50 mg and 75 mg for 4 weeks until a target platelet count was reached; after which interferon/ribavirin therapy commenced. During this phase, eltrombopag was administered for up to 12 weeks. Adverse events (AEs), ophthalmologic exams results, clinical laboratory data, physical exams, vital signs and ECGs were frequently assessed during the aforementioned studies. Collectively, 485 subjects were evaluated, including 354 on eltrombopag (in doses ranging from 30–100 mg for up to 16 weeks) and 131 on placebo. Overall, the proportion of subjects reporting AEs was generally comparable across all groups within the study including placebo (Table). For the ITP and HCV trials, mild headache was the most commonly occurring AE for all study groups including placebo. For the CIT trial, nausea was the most commonly reported AE and was reported related to the administration of chemotherapy. There was no apparent association between the administration of different doses of eltrombopag and clinically significant changes in data generated from AE reports, ophthalmologic evaluations, clinical laboratory data, physical exams, vital signs and ECGs. In conclusion, safety data from these four completed, randomized, placebo-controlled trials support further development of eltrombopag for thrombocytopenia of various etiologies. Ongoing safety monitoring will further characterize the safety profile of eltrombopag.
Patients Reporting Adverse Events PBO n (%) 30 mg n (%) 50 mg n (%) 75 mg n (%) 100 mg n (%) * reporting AEs ≥5%. † Reporting AEs in the eltrombopag only phase. Adverse Events Phase 2 ITP* 17 (59) 14 (47) 14 (47) 17 (61) Phase 3 ITP 14 (37) 45 (59) Phase 2 HCV† 10 (56) 11 (79) 10 (53) 13 (57) Phase 2 CIT 38 (83) 33 (75) 30 (68) 40 (87) Serious AEs Phase 3 ITP 8 7 Phase 2 HCV 1 3 1 2 Phase 2 CIT 9 4 8 10 Deaths Phase 2 ITP 0 0 1 0 Phase 3 ITP 0 0 Phase 2 HCV 1 0 0 0 Phase 2 CIT 3 0 3 3