The purpose of this study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics of a single dose of dextromethorphan in healthy adult subjects.
Subjects will check-in on Day -1 and remain confined to the clinical unit until Day 13. On the morning of Day 1, subjects will receive a single dose of dextromethorphan. On Days 6 and 7, subjects will receive isavuconazole three times daily (TID) administered approximately 8 hours apart. On Day 8 through 12, subjects will receive isavuconazole once daily (QD). On Day 10, subjects will receive a single dose of dextromethorphan. A follow-up visit will be scheduled on Day 21 (± 2 days).
Study Type
INTERVENTIONAL
Allocation
NA
Masking
NONE
Enrollment
24
oral
oral
Parexel
Baltimore, Maryland, United States
Pharmacokinetic (PK) profile for dextromethorphan (in plasma): AUCinf, Cmax , AUClast
Area under the concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf), maximum concentration (Cmax), and AUC from time of dosing to the last quantifiable concentration (AUClast).
Time frame: Pre-dose on Days 1 and 10, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 48 and 72 hours post-dose
PK profile for dextromethorphan (in plasma): t1/2, tmax, CL/F, and Vz/F
Apparent terminal elimination half-life (t1/2), time to attain Cmax (tmax), apparent body clearance after oral dosing (CL/F), and apparent volume of distribution (Vz/F)
Time frame: Pre-dose on Days 1 and 10, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 48 and 72 hours post-dose
PK profile for dextrorphan (in plasma): AUClast, AUCinf, Cmax, tmax, t1/2
Time frame: Pre-dose on Days 1 and 10, and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, 24, 48 and 72 hours post-dose
PK Isavuconazole (in plasma): trough concentration (Ctrough)
Time frame: Pre-dose on Days 8 and 12 and at 24 (Day 13) hours post-dose
PK profile for Isavuconazole (in plasma): AUCtau, Cmax, and tmax
AUC during time interval between consecutive dosing (AUCtau)
Time frame: Day 9 pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12,16, 20 hours post-dose and Day 10 pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 20, and 24 (Day 11) hours post-dose
Safety assessed by recording of adverse events, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs
Time frame: Day 1 through Day 13
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