Table 2.
SRK-181 GLP Multidose Toxicology and Toxicokinetic Studies in the Sprague-Dawley Rats and Cynomolgus Monkeys.
| Study | Number of animals | Groups | Dose route/volume | Dose levelsa | Samples for TK and cytokine analysisb | Samples for Clin pathc and ADA |
|---|---|---|---|---|---|---|
| Sprague-Dawley rats | 81 Males 81 Females |
15/sex/groupd
TK and ADA: 3/sex/group (control) and 6/sex/group (treated) |
IV bolus @ 5.0 mL/kg | 0, 30e, 100, 200 mg/kg once weekly for 4 weeks | Day 1: predose and 1, 24, and 96 hours postdose Day 15: predose and 1 hour postdose Day 22: predose and 1, 24, 96, and 120 hours postdose Day 29: predose and 1 hour postdose Once on days 8, 15, 22, and 29 (recovery phase) |
Clin Path: Day 30 (dosing phase) and day 29 (recovery phase) ADA: Days 1, 15, and 29 (dosing phase): predose and once on days 8, 15, 22, and 29 (recovery phase) |
| Cynomolgus monkeys | 20 Males 20 Females |
4-6/sex/groupf | IV bolus @ 6.0 mL/kg | 0, 30, 100, 300 mg/kg once weekly for 4 weeks | Day 1 and day 22: predose and 1, 24, 48, 96, and 120 hours postdose Day 8 and 15: predose Day 29: predose and 1 hour postdose Once on days 8, 15, 22, and 29 (recovery phase) |
Clin Path: Day 30 (dosing phase) and day 29 (recovery phase) ADA: Days 1, 15, 22, and 29 (dosing phase): predose and once on days 15 and 29 (recovery phase) |
Abbreviations: ADA, antidrug antibody; GLP, good laboratory practices; IV, intravenous; TK, toxicokinetic.
a Control group was dosed with vehicle.
b Cytokine analysis conducted for monkey study only. Samples from days 1 and 22 of the dosing phase (predose and 1 and 24 hours postdose samples only) were sent for cytokine analysis.
c Clinical pathology (clin path) included hematology, serum chemistry, coagulation, and urinalysis.
d 10/sex/group for dosing phase and 5/sex/group for recovery phase (recovery phase day 1 = dosing phase day 30).
e On day 1, animals in 30 mg/kg group received approximately 21 mg/kg dose (∼70.0% of the nominal 30 mg/kg dose).
f 4/sex/group for dosing phase across all dose levels and 2/sex/group for recovery phase in 300 mg/kg dose level only.