Table 56: Percentages of patients will have levels below 7.5 ng/mL predose (that is potentially sub-therapeutic concentrations) early in treatment in those patients who have ceased taking medication that is with no recent prior medication Second Predose Day 8 Predose Predose Day injection Day10 12 On Day 8 16 On Day 10 15 On Day 12 13 Table 57: Percentages of patients will have levels below 7.5 ng/mL predose (that is potentially sub-therapeutic concentrations) late in the first treatment cycle in those patients who have ceased taking medication that is with no recent prior medication Second injection Day Day Day 22 29 36 Day 4 8 13 16 Day 6 7 12 15 Day 8 4 11 15 Table 58: Maximum exposure (Cmax) in patients on oral paliperidone PR 6 mg for 5days (that is as per PI for patients not previously exposed) using the upper 90% limit for plasma concentration as pre dose level at initial injection Second injection Cmax ng/mL On Day 4 49.34 On Day 6 47.95 on Day 8 46.22 Prev max from 49.34 150/150a From R092670-PSY-1008 and -3006 150/150 mg eq on Day 1/Day 8 Second evaluation of clinical data submitted in response to questions Sponsor response: The PP1M population PK as published by Samtani et al. and described in the submitted PP1M population PK report should then be considered the representative description of paliperidone PK after PP1M administration. Therefore, the PK simulations performed using that model, including those mentioned by the evaluator should be still considered valid.
Table 56: Percentages of patients will have levels below 7.5 ng/mL predose (that is potentially sub-therapeutic concentrations) early in treatment in those patients who have ceased taking medication that is with no recent prior medication Second injection Predose Day 8 Predose Day10 Predose Day 12 On Day 8 16 On Day 10 15 On Day 12 13 Table 57: Percentages of patients will have levels below 7.5 ng/mL predose (that is potentially sub-therapeutic concentrations) late in the first treatment cycle in those patients who have ceased taking medication that is with no recent prior medication Second injection Day 22 Day 29 Day 36 Day 4 8 13 16 Day 6 7 12 15 Day 8 4 11 15 Table 58: Maximum exposure (Cmax) in patients on oral paliperidone PR 6 mg for 5days (that is as per PI for patients not previously exposed) using the upper 90% limit for plasma concentration as pre dose level at initial injection Second injection Cmax ng/mL On Day 4 49.34 On Day 6 47.95 on Day 8 46.22 Prev max from 150/150a 49.34 From R092670-PSY-1008 and -3006 150/150 mg eq on Day 1/Day 8 Second evaluation of clinical data submitted in response to questions Sponsor response: The PP1M population PK as published by Samtani et al. and described in the submitted PP1M population PK report should then be considered the representative description of paliperidone PK after PP1M administration. Therefore, the PK simulations performed using that model, including those mentioned by the evaluator should be still considered valid.
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