TABLE 15

Typical clinical study designs to determine whether a P450 inhibitor or inducer (marketed drug) would affect the PK of the NME

Order of Drug Administration and Data Collected

Dose
1. Administer NME as SD regimen and collect PK information 1. Standard therapeutic dose or high dose
2. Administer the known P450 inhibitora or inducer as an MD regimen until steady-state is achieved or maximal induction has occurred 2. Depends upon the inhibitor or inducer dose reported in the literature
3. Administer an SD of the NME + known inducer or inhibitor on the last days or final day, collect PK information of the NME (and perhaps of major active metabolites)
3. Same as in 1.
• a It is possible that a single dose of the known inhibitor may be sufficient; in this case a single dose study where the NME is given with and without the known P450 inhibitor with an appropriate washout period may be sufficient.