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Trial record 2 of 11 for:    rucaparib

Pharmacokinetic Drug-Drug Interaction Study of Rucaparib (DDI)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2016 by Clovis Oncology, Inc.
Sponsor:
Information provided by (Responsible Party):
Clovis Oncology, Inc.
ClinicalTrials.gov Identifier:
NCT02740712
First received: March 30, 2016
Last updated: April 19, 2016
Last verified: March 2016
  Purpose
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 Intervention Phase
Neoplasms
Drug: Caffeine
Drug: Warfarin
Drug: Omeprazole
Drug: Midazolam
Drug: digoxin
Drug: Vitamin K
Drug: Rucaparib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by Clovis Oncology, Inc.:

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 [ Time Frame: Days 1-5 and Days 12-16 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 1-5 and Days 12-16 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 1-5 and Days 12-16 ] [ Designated as safety issue: No ]
    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" [ Time Frame: Days 1-16 ] [ Designated as safety issue: Yes ]
    Incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications

  • PK parameters will be calculated for rucaparib at steady-state [ Time Frame: Day 7-12 ] [ Designated as safety issue: No ]
    Trough plasma concentration [Ctrough]

  • PK parameters will be calculated for rucaparib at steady-state [ Time Frame: Day 7-12 ] [ Designated as safety issue: No ]
    Maximum plasma concentration during a dosing interval at steady-state [Cmax,ss]

  • PK parameters will be calculated for rucaparib at steady-state [ Time Frame: Day 7-12 ] [ Designated as safety issue: No ]
    Time to attain maximum plasma concentration at steady-state [tmax,ss]

  • PK parameters will be calculated for rucaparib at steady-state [ Time Frame: Day 7-12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 1-5 and Days 12-16 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 1-5 and Days 12-16 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 1-5 and Days 12-16 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 1-5 and Days 12-16 ] [ Designated as safety issue: No ]
    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 [ Time Frame: From cycle 1 Day 1until radiologically confirmed disease progression, death, or initiation of subsequent treatment whichever comes first up to 52 weeks ] [ Designated as safety issue: No ]
    28 day cycles with response evaluation every 8 weeks(±7 days) until week 24 thereafter every 12 weeks (±14 days)


Estimated Enrollment: 16
Study Start Date: March 2016
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Marevan®
Drug: Omeprazole
40 mg Tablet
Other Name: Losec®; MUPS®
Drug: Midazolam
5 mg/mL
Other Name: Midazolam Accord®; versed
Drug: digoxin
.25 mg Tablet
Other Name: lanoxin®
Drug: Vitamin K
10 mg Tablet
Other Name: warfarin antagonist
Drug: Rucaparib
200 & 300 mg tablet
Other Name: rucaparib camsylate

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02740712

Contacts
Contact: Clovis Oncology Clinical Trial Information 1-855-262-3040 (USA) clovistrials@emergingmed.com
Contact: Clovis Oncology Clinical Trial Information +1-303-625-5160 (ex-USA) clovistrials@emergingmed.com

Locations
Poland
BioVirtus Research Site Recruiting
Kajetany, Mokra 7, Poland, 05-830
Contact: Katarzyna Jarus-Dziedzic, MD, PhD         
Principal Investigator: Katarzyna Jarus-Dziedzic, MD, PhD         
Med Polonia Not yet recruiting
Poznan, Poland, 60-693
Contact: Rodryg Ramlau, MD         
Zachodniopomorskie Centrum Onkologii Centrum Innowacji Recruiting
Szczecin, Poland, 71-730
Contact: Piotr Wysocki, MD, PhD         
Principal Investigator: Piotr Wysocki, MD, PhD         
Sponsors and Collaborators
Clovis Oncology, Inc.
Investigators
Study Director: Sergey Yurasov, MD Clovis Oncology
  More Information

Responsible Party: Clovis Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02740712     History of Changes
Other Study ID Numbers: CO-338-044 
Study First Received: March 30, 2016
Last Updated: April 19, 2016
Health Authority: European Union: European Medicines Agency

Keywords provided by Clovis Oncology, Inc.:
rucaparib
CO-338
Clovis
Clovis Oncology
PARP Inhibitor
Drug-Drug Interaction

Additional relevant MeSH terms:
Rucaparib
Vitamins
Vitamin K
Caffeine
Omeprazole
Digoxin
Midazolam
Warfarin
Micronutrients
Growth Substances
Physiological Effects of Drugs
Central Nervous System Stimulants
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Anticoagulants
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous

ClinicalTrials.gov processed this record on September 30, 2016