The primary objective is to evaluate the effect of rifampin, a potent cytochrome P450 3A4 inducer, at steady-state on the systemic exposure of a single dose of pacritinib in healthy subjects.
This was a single-center, open-label, one-way crossover, drug-interaction study. On Day 1, subjects received a single oral 400-mg dose of pacritinib. Following a 7-day washout period, 600-mg oral doses of rifampin were administered once daily (QD) on Days 8 through 17. It was anticipated that steady-state concentrations of rifampin would be achieved by Day 17. On Day 17, a single oral 400-mg dose of pacritinib was co-administered with the final 600-mg dose of rifampin.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
18
Subjects received a single oral 400-mg dose of pacritinib
Subjects received 600-mg oral doses of rifampin; administered QD following a 7-day washout period
On Day 17, a single oral 400-mg dose of pacritinib was co-administered with the final 600-mg dose of rifampin.
Covance Clinical Research Unit
Daytona Beach, Florida, United States
Estimate ratios of geometric mean values and the corresponding 90% confidence intervals (CIs) for pacritinib treatments with and without rifampin
Estimate ratios of geometric mean values and the corresponding 90% confidence intervals (CIs) for pacritinib treatments with and without rifampin to assess the potential for clinical interaction with CYP3A4 inducers.
Time frame: Approx. one month
Incidence of Treatment-Emergent Adverse Events
To compare the safety and tolerability of single doses of pacritinib alone and in the presence of steady-state rifampin in healthy subjects
Time frame: Day 1 to Day 24
The maximum plasma concentration (Cmax).
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule with or without rifampin in healthy subjects
Time frame: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose
The time to reach maximum plasma concentration (tmax)
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule with or without rifampin in healthy subjects
Time frame: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose
The area under the plasma concentration-time curve from time zero to time of the last measured concentration above the limit of quantification (AUC0-t)
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule with or without rifampin in healthy subjects
Time frame: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
The area under the plasma concentration-time curve from zero to infinity (AUC0-∞)
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule with or without rifampin in healthy subjects
Time frame: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose
The apparent terminal elimination rate constant (λZ) and the respective apparent terminal elimination half-life (t½)
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule with or without rifampin in healthy subjects
Time frame: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose
The apparent volume of distribution (Vd)
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule with or without rifampin in healthy subjects
Time frame: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose
The apparent total body clearance (CL/F)
The following pharmacokinetic parameters of pacritinib and major human metabolites were assessed following 400 mg single-dose administration of pacritinib capsule with or without rifampin in healthy subjects
Time frame: Plasma: 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose