This study will be a single center, open-label, drug-drug interaction study in healthy male and female subjects. The study will consist of 2 parts. In Part A, the effects of steady-state dosing of a strong CYP3A inhibitor (itraconazole) or inducer (rifampin) on the pharmacokinetics of E2006 and metabolites will be assessed. Approximately 30 subjects will be sequentially assigned to 1 of 2 treatment groups to receive itraconazole or rifampin in equal numbers (approximately 15 subjects per group). The itraconazole treatment group will be fully enrolled before enrollment is initiated for the rifampin treatment group. In Part B, the effects of steady-state dosing of E2006 on the pharmacokinetics of midazolam, a substrate of CYP3A, plus bupropion, a substrate of CYP2B6, will be assessed in approximately 24 subjects. The 2 study parts can be conducted in parallel.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
106
PPD Development LLC
Austin, Texas, United States
Pharmacokinetics of E2006 and its major metabolites, M4, M9, and M10 (Part A), and midazolam, bupropion, and the hydroxylated metabolite of bupropion (Part B): AUC(0-t)
Area under the concentration-time curve from zero time to time of last quantifiable concentration
Time frame: Approximately 56 Days for Part A; Approximately 42 Days for Part B
Pharmacokinetics of E2006 and its major metabolites, M4, M9, and M10 (Part A), and midazolam, bupropion, and the hydroxylated metabolite of bupropion (Part B): AUC(0-inf)
Area under the concentration-time curve from zero time extrapolated to infinite time
Time frame: Approximately 56 Days for Part A; Approximately 42 Days for Part B
Pharmacokinetics of E2006 and its major metabolites, M4, M9, and M10 (Part A), and midazolam, bupropion, and the hydroxylated metabolite of bupropion (Part B): Cmax
Maximum observed concentration
Time frame: Approximately 56 Days for Part A; Approximately 42 Days for Part B
Pharmacokinetics of E2006 and its major metabolites, M4, M9, and M10 (Part A), and midazolam, bupropion, and the hydroxylated metabolite of bupropion (Part B): tmax
Time at which the highest drug concentration occurs
Time frame: Approximately 56 Days for Part A; Approximately 42 Days for Part B
Pharmacokinetics of E2006: AUC(0-8h)
Area under the concentration-time curve from time zero time to 8 hours after dosing (E2006 only)
Time frame: Approximately 56 Days for Part A; Approximately 42 Days for Part B
Pharmacokinetics of E2006: AUC(0-24h)
Area under the concentration-time curve from time zero time to 24 hours after dosing (E2006 only)
Time frame: Approximately 56 Days for Part A; Approximately 42 Days for Part B
Pharmacokinetics of E2006 and its major metabolites, M4, M9, and M10 (Part A), and midazolam, bupropion, and the hydroxylated metabolite of bupropion (Part B): AUC(0-72h)
Area under the concentration-time curve from zero time to time 72 hours after dosing
Time frame: Approximately 56 Days for Part A; Approximately 42 Days for Part B
Pharmacokinetics of E2006 and its major metabolites, M4, M9, and M10 (Part A), and midazolam, bupropion, and the hydroxylated metabolite of bupropion (Part B): t1/2
Terminal elimination phase half-life
Time frame: Approximately 56 Days for Part A; Approximately 42 Days for Part B
Pharmacokinetics of E2006 and its major metabolites, M4, M9, and M10 (Part A), and midazolam, bupropion, and the hydroxylated metabolite of bupropion (Part B): CL/F
Apparent total clearance after extravascular administration
Time frame: Approximately 56 Days for Part A; Approximately 42 Days for Part B
Pharmacokinetics of E2006 and its major metabolites, M4, M9, and M10 (Part A), and midazolam, bupropion, and the hydroxylated metabolite of bupropion (Part B): AUC(0-inf), metabolite ratio
Ratio of S,S-hydroxybupropion to S-buproprion
Time frame: Approximately 56 Days for Part A; Approximately 42 Days for Part B
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