Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist

• Published in: Blood Vol. 109; no. 11; pp. 4739 - 4741
• Main Authors: Jenkins, Julian M., Williams, Daphne, Deng, Yanli, Uhl, Joanne, Kitchen, Valerie, Collins, David, Erickson-Miller, Connie L.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01-06-2007; The Americain Society of Hematology
• Subjects: Administration, Oral; Adult; Benzoates - pharmacokinetics; Benzoates - therapeutic use; Biological and medical sciences; Blood Platelets - drug effects; Dose-Response Relationship, Drug; Hematologic and hematopoietic diseases; Humans; Hydrazines - pharmacokinetics; Hydrazines - therapeutic use; Male; Medical sciences; Placebos; Platelet Count; Pyrazoles - pharmacokinetics; Pyrazoles - therapeutic use; Receptors, Thrombopoietin - agonists; Thrombocytopenia - drug therapy; Thrombopoiesis; Time Factors; Phase I trial; Agonist; Hematology; Thrombopoietin; Biological receptor
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-11-057968

Eltrombopag (SB-497 115) is a first-in-class, oral, small-molecule, nonpeptide agonist of the thrombopoietin receptor (TpoR), being developed as a treatment for thrombocytopenia of various etiologies. In this phase 1 placebo-controlled clinical trial in 73 healthy male subjects, eltrombopag was administered as once-daily oral capsules for 10 days at doses of 5, 10, 25, 30, 50, and 75 mg. The pharmacokinetics of eltrombopag were dose dependent and linear, and eltrombopag increased platelet counts in a dose-dependent manner. There were no apparent differences in the incidence or severity of adverse events in subjects receiving active or placebo study medication. These observations indicate that eltrombopag is a once-daily, oral TpoR agonist with demonstrated thrombopoietic activity in human subjects, encouraging further studies in patients with thrombocytopenia.