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 microg/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 microg/kg and 7 of 8 receiving 2 microg/kg had platelet count increases > or =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 microg/kg.
Kumagai
Yuji
Y
Kitasato University East Hospital, 2-1-1, Asamizodai, Sagamihara, Kanagawa, Japan 228-8520.
Fujita
Tomoe
T
Ozaki
Machiko
M
Sahashi
Kunihiko
K
Ohkura
Masayuki
M
Ohtsu
Tomoko
T
Arai
Yoshihiro
Y
Sonehara
Yusuke
Y
Nichol
Janet L
JL
D000328:Adult; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007279:Injections, Subcutaneous; D007564:Japan; D008297:Male; D010976:Platelet Count; D011961:Receptors, Fc / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins; D013926:Thrombopoietin
D002352:Carrier Proteins; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; D013926:Thrombopoietin; C488777:romiplostim