MedPath

Pharmacokinetic Drug-Drug Interaction Study of Rucaparib

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
Inclusion Criteria
  • 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
Read More
Exclusion Criteria
  • 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.
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
single arm probe drugs and rucaparibVitamin KCaffeine Warfarin Vitamin K Omeprazole Midazolam Digoxin rucaparib
single arm probe drugs and rucaparibdigoxinCaffeine Warfarin Vitamin K Omeprazole Midazolam Digoxin rucaparib
single arm probe drugs and rucaparibCaffeineCaffeine Warfarin Vitamin K Omeprazole Midazolam Digoxin rucaparib
single arm probe drugs and rucaparibWarfarinCaffeine Warfarin Vitamin K Omeprazole Midazolam Digoxin rucaparib
single arm probe drugs and rucaparibOmeprazoleCaffeine Warfarin Vitamin K Omeprazole Midazolam Digoxin rucaparib
single arm probe drugs and rucaparibMidazolamCaffeine Warfarin Vitamin K Omeprazole Midazolam Digoxin rucaparib
single arm probe drugs and rucaparibRucaparibCaffeine Warfarin Vitamin K Omeprazole Midazolam Digoxin rucaparib
Primary Outcome Measures
NameTimeMethod
PK parameters for caffeine, S-warfarin, omeprazole, midazolam, and digoxin with and without rucaparib treatment to be calculated from the plasma concentration-time dataDays 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
NameTimeMethod
PK parameters for caffeine, S-warfarin, omeprazole, midazolam, and digoxin with and without rucaparib treatment to be calculated from the plasma concentration-time dataDays 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-stateDay 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

© Copyright 2025. All Rights Reserved by MedPath