Avatrombopag, an oral thrombopoietin receptor agonist: results of two double-blind, dose-rising, placebo-controlled Phase 1 studies.

Avatrombopag is an oral thrombopoietin receptor agonist that has been recently approved for treating thrombocytopenia in chronic liver disease patients needing invasive procedures. Clinical trials supporting this new treatment were guided by two double-blind, dose-rising, placebo-controlled Phase 1 studies in healthy adults reported here that assessed safety, tolerability and pharmacokinetic profile of avatrombopag, and its effect on platelet counts. Subjects were randomised (2:1) in the single-dose study (N = 63) to avatrombopag (1, 3, 10, 20, 50, 75 and 100 mg) or placebo, and in the multiple-dose study (N = 29) to avatrombopag (3, 10 and 20 mg) or placebo daily for 14 days. There were no serious adverse events (AEs), dose-limiting toxicities, deaths, AEs causing withdrawal, thromboses or liver function abnormalities. In both studies, avatrombopag peak concentration and exposure increased proportionally relative to dose; half-life was 18-21 h and independent of dose, supporting once-daily dosing. Effects on platelet counts depended on dose, concentration and treatment duration. Platelet count increases began 3-5 days post-administration, with maximum changes of >370 × 109 /l over baseline with 20 mg daily after 13-16 days. These data support continued development of avatrombopag for treatment of other thrombocytopenic conditions and provide important guidance for the haematologist in the use of this new thrombopoietin receptor agonist.