Pharmacokinetic Drug-Drug Interaction Study of Rucaparib
- Conditions
- Neoplasms
- Interventions
- Registration Number
- NCT02740712
- Lead Sponsor
- pharmaand GmbH
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 17
- Histologically or cytologically confirmed advanced solid tumor
- Have evidence of measurable disease as defined by RECIST Version 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate bone marrow, renal, and liver function
- Prior treatment with chemotherapy, radiation, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or experimental drugs within 14 days prior to Day 1
- Prior treatment with any poly adenosine diphosphate ribose polymerase inhibitor (PARPi)
- Arterial or venous thrombi (including cerebrovascular accident), myocardial infarction, admission for unstable angina, cardiac angioplasty, stenting or poorly controlled hypertension within the last 3 months prior to Screening;
- Pre-existing duodenal stent, recent or existing bowel obstruction, and/or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of study drugs
- Current use of therapeutic anticoagulation (low molecular weight heparin, oral anticoagulant agents including acetylsalicylic acid),
- Current use of one of the probe drugs;
- Untreated or symptomatic central nervous system (CNS) metastases.
- Evidence or history of bleeding disorder
- Participation in another investigational drug trial within 30 days prior to Day 1 (or 5 times the half-life of the drug, whichever is longer) or exposure to more than three new investigational agents within 12 months prior to Day 1;
- Acute illness within 14 days prior to Day 1 unless mild in severity and approved by the Investigator and Sponsor's medical representative
- Active second malignancy, i.e., patient known to have potentially fatal cancer present for which they may be (but not necessarily) currently receiving treatment.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description single arm probe drugs and rucaparib Vitamin K Caffeine Warfarin Vitamin K Omeprazole Midazolam Digoxin rucaparib single arm probe drugs and rucaparib digoxin Caffeine Warfarin Vitamin K Omeprazole Midazolam Digoxin rucaparib single arm probe drugs and rucaparib Caffeine Caffeine Warfarin Vitamin K Omeprazole Midazolam Digoxin rucaparib single arm probe drugs and rucaparib Warfarin Caffeine Warfarin Vitamin K Omeprazole Midazolam Digoxin rucaparib single arm probe drugs and rucaparib Omeprazole Caffeine Warfarin Vitamin K Omeprazole Midazolam Digoxin rucaparib single arm probe drugs and rucaparib Midazolam Caffeine Warfarin Vitamin K Omeprazole Midazolam Digoxin rucaparib single arm probe drugs and rucaparib Rucaparib Caffeine Warfarin Vitamin K Omeprazole Midazolam Digoxin rucaparib
- Primary Outcome Measures
Name Time Method PK parameters for caffeine, S-warfarin, omeprazole, midazolam, and digoxin with and without rucaparib treatment to be calculated from the plasma concentration-time data Days 1-5 and Days 12-16 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 \[AUC0-last \]
- Secondary Outcome Measures
Name Time Method PK parameters for caffeine, S-warfarin, omeprazole, midazolam, and digoxin with and without rucaparib treatment to be calculated from the plasma concentration-time data Days 1-5 and Days 12-16 Apparent volume of distribution during terminal phase \[Vz/F\]
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" Days 1-16 Incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications
PK parameters will be calculated for rucaparib at steady-state Day 7-12 Area Under the Curve over a dosing interval τ at steady-state \[AUCτ,ss\]
Trial Locations
- Locations (3)
BioVirtus Research Site
🇵🇱Kajetany, Mokra 7, Poland
Zachodniopomorskie Centrum Onkologii Centrum Innowacji
🇵🇱Szczecin, Poland
Med Polonia
🇵🇱Poznan, Poland