Table 1.

Studies in cynomolgus monkeys

Study	n	Groups	Treatments	Samples collected	Assessments
Single-dose PK/PD #1	18 males	6 groups; 3 per group	Vehicle control i.v.; 0.01, 0.1, 1, or 3 mg·kg−1 AMG 181 i.v.; 3 mg·kg−1 AMG 181 s.c.	Blood samples collected 2–3 times pre-dose; 0.25, 3 and 6 h, and 1, 3, 7, 10, 14, 17, 21, 25, 28, 35, 42, 56 and 70 days post-dose	AMG 181 concentration (PK); haematology and/or flow cytology (PD); anti-AMG 181 binding antibody
Single-dose PK/PD #2	18 males	3 groups; 6 per group	Vehicle control i.v.; 9 mg·kg−1 AMG 181 i.v.; 9 mg·kg−1 AMG 181 s.c.	Blood samples collected 2–3 times pre-dose; 0.25, 3 and 6 h, and 1, 3, 7, 10, 14, 17, 21, 25, 28, 35, 42, 56 and 70 days post-dose	AMG 181 concentration (PK); haematology and/or flow cytology (PD); anti-AMG 181 binding antibody
Two-dose non-GLP toxicology	12 males 12 females	3 groups; 4 per sex per group	Vehicle control s.c. QW; 0.5 or 80 mg·kg−1 AMG 181 s.c. QW	Blood samples collected pre-dose and 0.25, 3, 8, 24, 72 and 168 h post-dose on study days 1 and 8; blood samples collected from recovery monkey (two per sex per group) 14, 17, 21, 25, 28, 35, 42, 49, 52, 56, 70, 84, 91, 105, 119, 133, 140, 148, 154, 161, 170, 175, 189 and 196 days post first dose	AMG 181 concentrations (TK); haematology and/or flow cytometry (PD); anti-AMG 181 binding antibody
Three month GLP toxicology	30 males 30 females	5 groups; 6 per sex per group	Vehicle control s.c. QW; 5, 20 or 80 mg·kg−1 s.c. QW; 80 mg·kg−1 i.v. QW	Blood samples collected pre-dose and 0.25, 3, 8, 24, 72 and 168 h post-dose on study days 1 and 8 and pre-dose 14, 28, 35, 56, and 84 days post first dose; blood samples collected from recovery monkeys (2 per sex per group) 112, 126, 140, 154, 168, 182, 196, 210, 224, 238, 252, 268, 280, 294, 308 and 322 days post first dose.	AMG 181 concentrations (TK); haematology and/or flow cytometry (PD); anti-AMG 181 binding and neutralizing antibodies

PD, pharmacodynamics; PK, pharmacokinetics; QW, once-weekly; TK, toxicokinetics.