Dog (Beagle) PO 37.5 40.8 Generally not found in humans 75 117 Generally not found in humans PSM1101 4 300 Generally not ≈9 found in Monkey PO humans 600 Generally not ≈18 found in humans 900 Generally not ≈18 found in humans PSM1140 39 Weeks 300 Generally not ≈40 in humans Monkey PO 600 Generally not ≈227 in humans 900 Generally not ≈376 found in humans * at study termination unless otherwise noted. Relative exposure margins for brivaracetam and its metabolites in juveniles Brivaracetam is not recommended for use in children <16 years of age. Although studies in juvenile animals were performed, no human AUC data for this developmental stage were submitted. Thus, relevant AUC ratios cannot be calculated. It should be noted that in juvenile animals (rats and dogs) total plasma exposure was generally similar to exposure in adult animals, except at PND 4 where approximately a 4X higher exposure was achieved in juvenile rats compared with adults. Relevant toxicokinetic data of brivaracetam and its metabolites in juvenile rats are shown below (NOAEL = 600 mg/kg/day). Table 13: PK parameter values of ucb 34714 and its metabolites in juvenile Wistar rats (male & female) after repeat administration of ucb 34714. Key toxicokinetic data for brivaracetam in juvenile dogs are shown below. 14: Mean PK parameter values of ucb 34714 in male & female juvenile beagle dogs after single and repeat oral administration of ucb 34714.
Dog (Beagle) PO 37.5 40.8 Generally not found in humans 75 117 Generally not found in humans PSM1101 Monkey 4 PO 300 ≈9 Generally not found in humans 600 ≈18 Generally not found in humans 900 ≈18 Generally not found in humans PSM1140 Monkey 39 Weeks PO 300 ≈40 Generally not in humans 600 ≈227 Generally not in humans 900 ≈376 Generally not found in humans * at study termination unless otherwise noted. Relative exposure margins for brivaracetam and its metabolites in juveniles Brivaracetam is not recommended for use in children <16 years of age. Although studies in juvenile animals were performed, no human AUC data for this developmental stage were submitted. Thus, relevant AUC ratios cannot be calculated. It should be noted that in juvenile animals (rats and dogs) total plasma exposure was generally similar to exposure in adult animals, except at PND 4 where approximately a 4X higher exposure was achieved in juvenile rats compared with adults. Relevant toxicokinetic data of brivaracetam and its metabolites in juvenile rats are shown below (NOAEL = 600 mg/kg/day). Table 13: PK parameter values of ucb 34714 and its metabolites in juvenile Wistar rats (male & female) after repeat administration of ucb 34714. Key toxicokinetic data for brivaracetam in juvenile dogs are shown below. 14: Mean PK parameter values of ucb 34714 in male & female juvenile beagle dogs after single and repeat oral administration of ucb 34714.
auspar-brivaracetam-170307.docx