Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 31 of 48 for:    rucaparib

Pharmacokinetic Drug-Drug Interaction Study of Rucaparib (DDI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02740712
Recruitment Status : Active, not recruiting
First Posted : April 15, 2016
Last Update Posted : May 30, 2019
Sponsor:
Information provided by (Responsible Party):
Clovis Oncology, Inc.

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
Neoplasms Drug: Caffeine Drug: Warfarin Drug: Omeprazole Drug: Midazolam Drug: digoxin Drug: Vitamin K Drug: Rucaparib 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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: Open Label
Primary Purpose: Other
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
Actual Study Start Date : March 2016
Actual Primary Completion Date : March 2017
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 Names:
  • rucaparib camsylate
  • Rubraca
  • CO-338




Primary Outcome Measures :
  1. 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 ]
    Maximum plasma concentration [Cmax]

  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 ]
    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 :
  1. 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 ]
    Area Under the Curve, from time zero up to infinity with extrapolation of the terminal phase [AUC0-inf]

  2. 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 ]
    Incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications

  3. PK parameters will be calculated for rucaparib at steady-state [ Time Frame: Day 7-12 ]
    Trough plasma concentration [Ctrough]

  4. PK parameters will be calculated for rucaparib at steady-state [ Time Frame: Day 7-12 ]
    Maximum plasma concentration during a dosing interval at steady-state [Cmax,ss]

  5. PK parameters will be calculated for rucaparib at steady-state [ Time Frame: Day 7-12 ]
    Time to attain maximum plasma concentration at steady-state [tmax,ss]

  6. PK parameters will be calculated for rucaparib at steady-state [ Time Frame: Day 7-12 ]
    Area Under the Curve over a dosing interval τ at steady-state [AUCτ,ss]

  7. 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 ]
    Terminal half-life [t1/2]

  8. 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 ]
    Time to attain maximum plasma concentration [tmax]

  9. 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 ]
    Apparent clearance [CL/F]

  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 [ Time Frame: Days 1-5 and Days 12-16 ]
    Apparent volume of distribution during terminal phase [Vz/F]


Other Outcome Measures:
  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 [ Time Frame: 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)



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02740712


Locations
Layout table for location information
Poland
BioVirtus Research Site
Kajetany, Mokra 7, Poland, 05-830
Med Polonia
Poznan, Poland, 60-693
Zachodniopomorskie Centrum Onkologii Centrum Innowacji
Szczecin, Poland, 71-730
Sponsors and Collaborators
Clovis Oncology, Inc.

Layout table for additonal information
Responsible Party: Clovis Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02740712     History of Changes
Other Study ID Numbers: CO-338-044
First Posted: April 15, 2016    Key Record Dates
Last Update Posted: May 30, 2019
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

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