The objective of this study is to evaluate the effect of multiple doses of vorasidenib on single-dose PK of bupropion as an index substrate of CYP2B6, flurbiprofen as an index substrate of CYP2C9, omeprazole as an index substrate of CYP2C19, repaglinide as an index substrate of CYP2C8, midazolam as an index substrate of CYP3A4, and rosuvastatin as a substrate of BCRP in healthy adult participants. The study consists of screening, two treatment periods in-house, and a follow-up period. During the first period, Day 1 through Day 7, participants will receive CYPs and BCRP index substrates alone and during the second treatment period, Day 8 through Day 28, these will be administered in combination with vorasidenib. Participation in the study will be up to 87 days from screening through the follow up period. Study activities may include blood tests, ECG, vital signs, and a physical examination.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
28
40mg taken orally daily from Day 8 through Day 28
150mg taken orally on Day 2 and Day 23
50mg taken orally on Day 1 and Day 22
20mg taken orally on Day 1 and Day 22
2mg taken orally on Day 1 and Day 22
0.5mg taken orally on Day 1 and Day 22
10mg taken orally on Day 5 and Day 26
Celerion
Belfast, United Kingdom
Maximum concentration (Cmax) of bupropion and its metabolite hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, and rosuvastatin
Time frame: Through Day 29
Area under the plasma concentration versus time curve from time 0 to the last quantifiable concentration (AUC0-last) of bupropion and its metabolite hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, and rosuvastatin
Time frame: Through Day 29
Area under the plasma concentration versus time curve from 0 extrapolated to infinity (AUC0-inf) of bupropion and its metabolite hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, and rosuvastatin
Time frame: Through Day 29
Time corresponding to Cmax (Tmax) of bupropion and its metabolite hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, and rosuvastatin
Time frame: Through Day 29
Terminal half-life (t1/2) of bupropion and its metabolite hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, and rosuvastatin
Time frame: Through Day 29
Apparent oral clearance (CL/F) of bupropion and its metabolite hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, and rosuvastatin
Time frame: Through Day 29
Apparent volume of distribution during the terminal phase following oral administration (Vz/F) of bupropion and its metabolite hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, and rosuvastatin
Time frame: Through Day 29
Elimination rate constant (Kel) of bupropion and its metabolite hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, and rosuvastatin
Time frame: Through Day 29
Number of Adverse Events (AEs)
Time frame: Through the Follow-up Phone Call (Day 57)
Trough plasma concentration (Ctrough) of vorasidenib
Time frame: Through Day 29
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