Pharmacodynamics and Pharmacokinetics of AMG 531, a Thrombopoiesis‐Stimulating Peptibody, in Healthy Japanese Subjects: A Randomized, Placebo‐Controlled Study

AMG 531 is a novel thrombopoiesis‐stimulating peptibody being investigated for the treatment of chronic immune thrombocytopenic purpura. This double‐blind, phase I study evaluated the safety, pharmacodynamics, and pharmacokinetics of AMG 531 in healthy Japanese men. Thirty subjects were randomly assigned 4:1 (AMG 531/placebo) to receive 1 dose of AMG 531 (0.3, 1, or 2 μg/kg) or placebo by subcutaneous injection; subjects were evaluated for 6 weeks. AMG 531 was generally well tolerated, with adverse events similar to placebo. Treatment‐related adverse events (headache, “feeling hot,” malaise) were reported for 5 of 24 AMG 531‐treated subjects. Platelets generated after exposure to AMG 531 functioned normally. Four of 8 subjects receiving 1 μg/kg and 7 of 8 receiving 2 μ/kg had platelet count increases ≥1.5‐fold over baseline, an effect similar to that seen in non‐Japanese subjects. Serum AMG 531 concentrations were below the lower limit of quantification in all but 2 subjects receiving 2 μg/kg.