This will be an open-label, single-center, crossover, one-way, drug-interaction study to evaluate the effect of 500 mg clarithromycin BID (dosed to steady state) on the PK of a single 400-mg dose of pacritinib in healthy male and female 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. On Day 8 through the morning of Day 12, following a 7-day washout period, 500-mg oral doses of clarithromycin were administered twice daily (BID), 8 to 12 hours apart. It was anticipated that steady-state concentrations of clarithromycin would be achieved by Day 12. On Day 12, a single oral 400-mg dose of pacritinib was co-administered with the final 500-mg dose of clarithromycin.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
20
Single 400-mg dose (four 100-mg capsules) administered in the morning on Days 1 and 12
Twice-daily, 500-mg dose (one 500-mg tablet) administered every 8 to 12 hours on Day 8 through the morning of Day 12
On Day 12, a single oral 400-mg dose of pacritinib was co-administered with the final 500-mg dose of clarithromycin
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 clarithromycin
To estimate ratios of geometric mean values and the corresponding 90% confidence intervals
Time frame: Fifteen days approximately
Incidence of Treatment-Emergent Adverse Events
To evaluate the safety of pacritinib and tolerability of a single 400 mg dose of pacritinib in patients with hepatic impairment. Safety endpoints for this study include AEs, vital signs, clinical laboratory evaluations, physical examinations, and single 12-lead ECGs
Time frame: from Day 1 to Day 19
The apparent terminal elimination rate constant (λZ) and the respective apparent terminal elimination half-life (t½).
Time frame: Plasma (Day 1 and 12): 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose
The maximum plasma concentration (Cmax).
To characterize the pharmacokinetic (PK) profile of pacritinib and its major human metabolites following single-dose administration with and without concomitant clarithromycin in healthy subjects
Time frame: Plasma (Day 1 and 12): 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).
To characterize the pharmacokinetic (PK) profile of pacritinib and its major human metabolites following single-dose administration with and without concomitant clarithromycin in healthy subjects
Time frame: Plasma (Day 1 and 12): 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)
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To characterize the pharmacokinetic (PK) profile of pacritinib and its major human metabolites following single-dose administration with and without concomitant clarithromycin in healthy subjects
Time frame: Plasma (Day 1 and 12): 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 zero to infinity (AUC0-∞).
Time frame: Plasma (Day 1 and 12): 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).
Time frame: Plasma (Day 1 and 12): 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).
Time frame: Plasma (Day 1 and 12): 0, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 144, and 168 hrs post-dose