The purpose of this two part study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics of multiple doses of lopinavir/ritonavir and the effect of multiple doses of lopinavir/ritonavir on the pharmacokinetics of isavuconazole. Part 1 of the study includes 12 subjects randomized to receive either isavuconazole alone or isavuconazole in combination with lopinavir/ritonavir. The purpose of Part 1 is to evaluate safety and tolerability and to establish the effect of multiple doses of lopinavir/ritonavir on isavuconazole. Part 2, if initiated, includes 54 subjects randomized to receive isavuconazole alone, lopinavir/ritonavir alone, or isavuconazole in combination with lopinavir/ritonavir.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
NONE
Enrollment
68
oral
oral
Parexel International
Glendale, California, United States
Pharmacokinetic (PK) for isavuconazole: AUCtau
(Arms 1 and 3) Area under the concentration time curve during the during time interval between consecutive dosing (AUCtau) (tau=24)
Time frame: Part 1, Day 13: predose, 0.5, 1, 2, 3, 4, 6, 8,10,12,16, and 24 hours post-dose
Pharmacokinetic (PK) profile for isavuconazole: AUC tau and Cmax
(Arms 2 and 3) Maximum concentration (Cmax)
Time frame: Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post dose
Pharmacokinetic (PK) profile for lopinavir/ritonavir: AUC tau and Cmax
(Arms 2 and 3) AUC during time interval between consecutive dosing (AUCtau) (tau=12)
Time frame: Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours post dose
PK for isavuconazole (in plasma): trough concentration (Ctrough)
(Arms 1 and 3)
Time frame: Parts 1 and 2, Days 3, 5, 7, 9 and 11: pre-dose
PK profile for isavuconazole (in plasma): Cmax, tmax
(Arms 1 and 3) Time to attain Cmax (tmax)
Time frame: Parts 1 and 2, Day 13: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12,16, and 24 hours post-dose
PK for lopinavir/ritonavir (in plasma): trough concentration (Ctrough)
(Arms 2 and 3)
Time frame: Part 2, Days 3, 5, 7, 9 and 11: pre-dose
PK for lopinavir/ritonavir (in plasma): tmax
(Arms 2 and 3)
Time frame: Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours post dose
Safety and tolerability of isavuconazole alone and in combination with lopinavir (LPV) and ritonavir (RTV) assessed by recording of adverse events, physical examination, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs
Time frame: Part 1, Days 1 - 20 ± 2
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