Pharmacokinetic Drug-Drug Interaction Study of Rucaparib

NCT02740712 | Completed Phase 1

• 1 other identifier: CO-338-044
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 3

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.

Conditions

Neoplasms

Keywords

rucaparib; CO-338; Clovis; Clovis Oncology; PARP Inhibitor; Drug-Drug Interaction

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (10)

• 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

• 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

• PK parameters will be calculated for rucaparib at steady-state

  Day 7-12

• PK parameters will be calculated for rucaparib at steady-state

  Day 7-12

• PK parameters will be calculated for rucaparib at steady-state

  Day 7-12

Other Outcomes (1)

• 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

  From cycle 1 Day 1until radiologically confirmed disease progression, death, or initiation of subsequent treatment whichever comes first up to 52 weeks

Study Arms (1)

single arm probe drugs and rucaparib

OTHER

Caffeine Warfarin Vitamin K Omeprazole Midazolam Digoxin rucaparib

Drug: Caffeine; Drug: Warfarin; Drug: Omeprazole; Drug: Midazolam; Drug: digoxin; Drug: Vitamin K; Drug: Rucaparib

Interventions

Caffeine DRUG

200 mg (4 x 50mg) Tablet

single arm probe drugs and rucaparib

Warfarin DRUG

10 mg (2 x 5mg) Tablet

Also known as: Marevan®

single arm probe drugs and rucaparib

Omeprazole DRUG

40 mg Tablet

Also known as: Losec®; MUPS®

single arm probe drugs and rucaparib

Midazolam DRUG

5 mg/mL

Also known as: Midazolam Accord®; versed

single arm probe drugs and rucaparib

digoxin DRUG

.25 mg Tablet

Also known as: lanoxin®

single arm probe drugs and rucaparib

Vitamin K DRUG

10 mg Tablet

Also known as: warfarin antagonist

single arm probe drugs and rucaparib

Rucaparib DRUG

200 \& 300 mg tablet

Also known as: rucaparib camsylate, Rubraca, CO-338

single arm probe drugs and rucaparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• pharmaand GmbH: lead

Study Sites (3)

BioVirtus Research Site

Kajetany, Mokra 7, 05-830, Poland

Location

Med Polonia

Poznan, 60-693, Poland

Location

Zachodniopomorskie Centrum Onkologii Centrum Innowacji

Szczecin, 71-730, Poland

Location

Related Publications (1)

• Xiao JJ, Nowak D, Ramlau R, Tomaszewska-Kiecana M, Wysocki PJ, Isaacson J, Beltman J, Nash E, Kaczanowski R, Arold G, Watkins S. Evaluation of Drug-Drug Interactions of Rucaparib and CYP1A2, CYP2C9, CYP2C19, CYP3A, and P-gp Substrates in Patients With an Advanced Solid Tumor. Clin Transl Sci. 2019 Jan;12(1):58-65. doi: 10.1111/cts.12600. Epub 2018 Dec 20.

  PMID: 30427584 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

Caffeine; Warfarin; Omeprazole; major urinary proteins; Midazolam; Digoxin; Vitamin K; rucaparib

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Benzimidazoles; Benzodiazepines; Benzazepines; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Naphthoquinones; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phytol; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2016
• First Posted: April 15, 2016
• Study Start: April 1, 2016
• Primary Completion: March 1, 2017
• Study Completion: September 1, 2019
• Last Updated: June 9, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

PL (3)