TABLE 3

Simulated trials

Type of SimulationTrial DescriptionReference
Model development
Study CLBH589B2101: A phase IA, two-arm, multicenter, dose-escalation study of panobinostat administered orally on two dose schedules in adult patients with advanced solid tumors or non-Hodgkin’s lymphoma(http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf)
Study CLBH589B2102: Phase IA/II, two-arm, open-label, dose-escalation study of oral panobinostat administered via two dosing schedules with advanced hematologic malignanciesDeAngelo et al. 2013, (http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf)
Study CLBH589B2110: Effect of KTZ-mediated CYP3A4 inhibition on clinical PK of panobinostat in patientsHamberg et al. (2011), (http://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205353Orig1s000ClinPharmR.pdf)
Model verificationStudy CLBH589B2207: Phase Ib study of panobinostat and bortezomib in relapsed or relapsed and refractory multiple myeloma (exposure of panobinostat in combination with DEX)San-Miguel et al. (2013), Mu et al. (2016)
Model application
Simulated effect of RIF (600 mg dailky) dosed for 14 days on the PK of panobinostat (20 mg single dose) on day 7
Simulated effect of panobinostat (20 mg) dosed orally on Monday, Wednesday, Friday for 2 wk on the PK of MDZ (5-mg single dose) on day 15