The purpose of this study is to assess pharmacokinetic concentrations of multiple probes alone followed by assessment of the same drug pharmacokinetic concentrations when the patient has steady-state exposure to rucaparib followed by cycle-by-cycle treatment with rucaparib continuing until disease progression or other reason for discontinuation.
This is a Phase 1, open-label, sequential, drug-drug-interaction (DDI) study in patients with advanced solid tumors. The study will consist of 2 parts: a DDI part (Part I) and a rucaparib treatment part (Part II). In Part I, the PK of cytochrome P450 (CYP) cocktail probes: caffeine, S-warfarin, omeprazole, and midazolam and a P-glycoprotein probe (digoxin) will be assessed with and without rucaparib treatment. Patients will receive single doses of CYP drug cocktail (caffeine, warfarin, omeprazole, and midazolam) on Day 1 and Day 12, and single doses of digoxin on Day 2 and Day 13. Continuous treatment with 600 mg rucaparib twice daily (BID) will start on Day 5 and will last until at least Day 16 of Part I. In Part II, the treatment with rucaparib in 28-day cycles will continue until progression of disease, unacceptable toxicity, or other reason for discontinuation.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
17
BioVirtus Research Site
Kajetany, Mokra 7, Poland
Med Polonia
Poznan, Poland
Zachodniopomorskie Centrum Onkologii Centrum Innowacji
Szczecin, Poland
PK parameters for caffeine, S-warfarin, omeprazole, midazolam, and digoxin with and without rucaparib treatment to be calculated from the plasma concentration-time data
Maximum plasma concentration \[Cmax\]
Time frame: Days 1-5 and Days 12-16
PK parameters for caffeine, S-warfarin, omeprazole, midazolam, and digoxin with and without rucaparib treatment to be calculated from the plasma concentration-time data
Area under the concentration-time curve (AUC) up to time t, where t is the last time point with concentrations above the lower limit of quantitation \[AUC0-last \]
Time frame: Days 1-5 and Days 12-16
PK parameters for caffeine, S-warfarin, omeprazole, midazolam, and digoxin with and without rucaparib treatment to be calculated from the plasma concentration-time data
Area Under the Curve, from time zero up to infinity with extrapolation of the terminal phase \[AUC0-inf\]
Time frame: Days 1-5 and Days 12-16
Tolerability and safety of rucaparib with and without co-administration of the probe drugs assessed by incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications"
Incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications
Time frame: Days 1-16
PK parameters will be calculated for rucaparib at steady-state
Trough plasma concentration \[Ctrough\]
Time frame: Day 7-12
PK parameters will be calculated for rucaparib at steady-state
Maximum plasma concentration during a dosing interval at steady-state \[Cmax,ss\]
Time frame: Day 7-12
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5 mg/mL
.25 mg Tablet
10 mg Tablet
200 \& 300 mg tablet
PK parameters will be calculated for rucaparib at steady-state
Time to attain maximum plasma concentration at steady-state \[tmax,ss\]
Time frame: Day 7-12
PK parameters will be calculated for rucaparib at steady-state
Area Under the Curve over a dosing interval τ at steady-state \[AUCτ,ss\]
Time frame: Day 7-12
PK parameters for caffeine, S-warfarin, omeprazole, midazolam, and digoxin with and without rucaparib treatment to be calculated from the plasma concentration-time data
Terminal half-life \[t1/2\]
Time frame: Days 1-5 and Days 12-16
PK parameters for caffeine, S-warfarin, omeprazole, midazolam, and digoxin with and without rucaparib treatment to be calculated from the plasma concentration-time data
Time to attain maximum plasma concentration \[tmax\]
Time frame: Days 1-5 and Days 12-16
PK parameters for caffeine, S-warfarin, omeprazole, midazolam, and digoxin with and without rucaparib treatment to be calculated from the plasma concentration-time data
Apparent clearance \[CL/F\]
Time frame: Days 1-5 and Days 12-16
PK parameters for caffeine, S-warfarin, omeprazole, midazolam, and digoxin with and without rucaparib treatment to be calculated from the plasma concentration-time data
Apparent volume of distribution during terminal phase \[Vz/F\]
Time frame: Days 1-5 and Days 12-16