Table 1.
Threshold concentrations of BPU and metabolites for continuation of therapy on 150 mg dose level. Patients would have study drug held for >3 weeks, and then re-started at 50% (75 mg) if any of the following were exceeded a:
| Week | BPU | mmBPU | ||
|---|---|---|---|---|
|
Cmin (nM) |
AUC (μg*h/mL) |
Cmin (nM) |
AUC (μg*h/mL) |
|
| 2-4 | >60 | >400 | ||
| 4 | >15 | >100 | ||
| 5-12 | >60 | >600 | ||
| >12b | - | - | - | - |
a
IRB-approved thresholds were empirically chosen based on visual inspection of figures 2-3 for the protocol amendment subsequent to the grade 5 event at the 320 mg dose level.
b
Patients would not be discontinued from the study for PK thresholds after 12 weeks since by definition some type of clinical benefit (even stable disease) would have been achieved.