DDI: Pharmacokinetic Drug-Drug Interaction Study of Rucaparib
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: single arm probe drugs and rucaparib Caffeine Warfarin Vitamin K Omeprazole Midazolam Digoxin rucaparib |
Drug: Caffeine
200 mg (4 x 50mg) Tablet
Drug: Warfarin
10 mg (2 x 5mg) Tablet
Other Names:
Drug: Omeprazole
40 mg Tablet
Other Names:
Drug: Midazolam
5 mg/mL
Other Names:
Drug: digoxin
.25 mg Tablet
Other Names:
Drug: Vitamin K
10 mg Tablet
Other Names:
Drug: Rucaparib
200 & 300 mg tablet
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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]
Maximum plasma concentration [Cmax]
- 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
- 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 Curve, from time zero up to infinity with extrapolation of the terminal phase [AUC0-inf]
- 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]
Trough plasma concentration [Ctrough]
- PK parameters will be calculated for rucaparib at steady-state [Day 7-12]
Maximum plasma concentration during a dosing interval at steady-state [Cmax,ss]
- PK parameters will be calculated for rucaparib at steady-state [Day 7-12]
Time to attain maximum plasma concentration at steady-state [tmax,ss]
- 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]
- 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]
Terminal half-life [t1/2]
- PK parameters for caffeine, S-warfarin, omeprazole, midazolam, and digoxin with and without rucaparib treatment to be calculated from the plasma concentration-time data [Days 1-5 and Days 12-16]
Time to attain maximum plasma concentration [tmax]
- 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 clearance [CL/F]
- 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]
Other Outcome Measures
- 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]
28 day cycles with response evaluation every 8 weeks(±7 days) until week 24 thereafter every 12 weeks (±14 days)
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | BioVirtus Research Site | Kajetany | Mokra 7 | Poland | 05-830 |
| 2 | Med Polonia | Poznan | Poland | 60-693 | |
| 3 | Zachodniopomorskie Centrum Onkologii Centrum Innowacji | Szczecin | Poland | 71-730 |
Sponsors and Collaborators
- Clovis Oncology, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CO-338-044