Pharmacokinetic Drug-Drug Interaction Study of Rucaparib

Neoplasms Clinical Trial

— DDI  

Official title:

A Phase 1, Open-label, Multiple-probe Drug-drug Interaction Study to Determine the Effect of Rucaparib on Pharmacokinetics of Caffeine, S-Warfarin, Omeprazole, Midazolam, and Digoxin in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02740712
• Other study ID #: CO-338-044
• Status: Completed
• Phase: Phase 1
• Start date: April 2016
• Est. completion date: September 2019

Study information

• Verified date: June 2023
• Source: zr Pharma & GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: September 2019
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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.

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• Caffeine
200 mg (4 x 50mg) Tablet
• Warfarin
10 mg (2 x 5mg) Tablet
• Omeprazole
40 mg Tablet
• Midazolam
5 mg/mL
• digoxin
.25 mg Tablet
• Vitamin K
10 mg Tablet
• Rucaparib
200 & 300 mg tablet

Locations

Country	Name	City	State
Poland	BioVirtus Research Site	Kajetany	Mokra 7
Poland	Med Polonia	Poznan
Poland	Zachodniopomorskie Centrum Onkologii Centrum Innowacji	Szczecin

Sponsors (1)

Lead Sponsor	Collaborator
zr Pharma & GmbH

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Response will be determined using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and tumor markers per applicable criteria for a given tumor type	28 day cycles with response evaluation every 8 weeks(±7 days) until week 24 thereafter every 12 weeks (±14 days)	From cycle 1 Day 1until radiologically confirmed disease progression, death, or initiation of subsequent treatment whichever comes first up to 52 weeks
Primary	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]	Days 1-5 and Days 12-16
Primary	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 ]	Days 1-5 and Days 12-16
Secondary	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]	Days 1-5 and Days 12-16
Secondary	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	Days 1-16
Secondary	PK parameters will be calculated for rucaparib at steady-state	Trough plasma concentration [Ctrough]	Day 7-12
Secondary	PK parameters will be calculated for rucaparib at steady-state	Maximum plasma concentration during a dosing interval at steady-state [Cmax,ss]	Day 7-12
Secondary	PK parameters will be calculated for rucaparib at steady-state	Time to attain maximum plasma concentration at steady-state [tmax,ss]	Day 7-12
Secondary	PK parameters will be calculated for rucaparib at steady-state	Area Under the Curve over a dosing interval t at steady-state [AUCt,ss]	Day 7-12
Secondary	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]	Days 1-5 and Days 12-16
Secondary	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]	Days 1-5 and Days 12-16
Secondary	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]	Days 1-5 and Days 12-16
Secondary	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]	Days 1-5 and Days 12-16