NeoplasmsPhase 1DDINCT02740712
Pharmacokinetic Drug-Drug Interaction Study of Rucaparib
A Phase 1 study testing Caffeine, Warfarin and Omeprazole in people with Neoplasms, run by pharmaand GmbH at 3 sites in Poland.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- Caffeine, Warfarin and Omeprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 3 sitesPoland
- Study dates
- Apr 2016to Sep 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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;
Show all 11Show fewer
- 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.
Trial locations and contacts
3 sites in 1 country.
Poland3 sites
BioVirtus Research Site
Kajetany, Mokra 7, 05-830
Med Polonia
Poznan, 60-693
Zachodniopomorskie Centrum Onkologii Centrum Innowacji
Szczecin, 71-730
About this study
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
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.
Read the 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.
- Conditions
- Neoplasms
- Being tested
- Caffeine, Warfarin, Omeprazole, Midazolam, digoxin
- Keywords
- rucaparib, CO-338, Clovis, Clovis Oncology, PARP Inhibitor, Drug-Drug Interaction
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CaffeineDrug
200 mg (4 x 50mg) Tablet
WarfarinDrug
Also called Marevan®
10 mg (2 x 5mg) Tablet
OmeprazoleDrug
Also called Losec®; MUPS®
40 mg Tablet
MidazolamDrug
Also called Midazolam Accord®; versed
5 mg/mL
digoxinDrug
Also called lanoxin®
.25 mg Tablet
Vitamin KDrug
Also called warfarin antagonist
10 mg Tablet
RucaparibDrug
Also called rucaparib camsylate, Rubraca, CO-338
200 \& 300 mg tablet
| Study group | Role | What they receive |
|---|---|---|
| single arm probe drugs and rucaparib | Other | Caffeine Warfarin Vitamin K Omeprazole Midazolam Digoxin rucaparib Receives: Drug: Caffeine; Drug: Warfarin; Drug: Omeprazole; Drug: Midazolam; Drug: digoxin; Drug: Vitamin K; Drug: Rucaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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]
Measured: 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 ]
Measured: 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
Area Under the Curve, from time zero up to infinity with extrapolation of the terminal phase [AUC0-inf]
Measured: 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"
Incidence of Adverse Events (AEs), clinical laboratory abnormalities, and dose modifications
Measured: Days 1-16
PK parameters will be calculated for rucaparib at steady-state
Trough plasma concentration [Ctrough]
Measured: Day 7-12
PK parameters will be calculated for rucaparib at steady-state
Maximum plasma concentration during a dosing interval at steady-state [Cmax,ss]
Measured: Day 7-12
PK parameters will be calculated for rucaparib at steady-state
Time to attain maximum plasma concentration at steady-state [tmax,ss]
Measured: Day 7-12
PK parameters will be calculated for rucaparib at steady-state
Area Under the Curve over a dosing interval τ at steady-state [AUCτ,ss]
Measured: Day 7-12
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]
Measured: 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
Time to attain maximum plasma concentration [tmax]
Measured: 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
Apparent clearance [CL/F]
Measured: 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
Apparent volume of distribution during terminal phase [Vz/F]
Measured: Days 1-5 and Days 12-16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2016 (estimated)
- Study startApr 2016
- Primary completionMar 2017
- Study completionSep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- pharmaand GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02740712
- Sponsor's protocol ID
- CO-338-044
- Acronym
- DDI
- Status last verified
- Jun 2023
- First submitted
- 30 Mar 2016
- Last updated
- 9 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 30427584
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02740712
- Acronym / sponsor ID
- DDI / CO-338-044
- Conditions
- Neoplasms
- Keywords
- rucaparib, CO-338, Clovis, Clovis Oncology, PARP Inhibitor, Drug-Drug Interaction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- pharmaand GmbHIndustry (pharma, biotech, devices)
- Study start
- Apr 2016 (actual)
- Primary completion
- Mar 2017 (actual)
- Study completion
- Sep 2019 (actual)
- First posted
- 15 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| single arm probe drugs and rucaparib | Other | Drug: Caffeine, Drug: Warfarin, Drug: Omeprazole, Drug: Midazolam, Drug: digoxin, Drug: Vitamin K, Drug: RucaparibCaffeine Warfarin Vitamin K Omeprazole Midazolam Digoxin rucaparib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (11 listed)
- 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),
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Caffeine200 mg (4 x 50mg) Tablet | Drug | single arm probe drugs and rucaparib |
| WarfarinAlso: Marevan®10 mg (2 x 5mg) Tablet | Drug | single arm probe drugs and rucaparib |
| OmeprazoleAlso: Losec®; MUPS®40 mg Tablet | Drug | single arm probe drugs and rucaparib |
| MidazolamAlso: Midazolam Accord®; versed5 mg/mL | Drug | single arm probe drugs and rucaparib |
| digoxinAlso: lanoxin®.25 mg Tablet | Drug | single arm probe drugs and rucaparib |
| Vitamin KAlso: warfarin antagonist10 mg Tablet | Drug | single arm probe drugs and rucaparib |
| RucaparibAlso: rucaparib camsylate, Rubraca, CO-338200 \& 300 mg tablet | Drug | single arm probe drugs and rucaparib |
Primary outcome
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]
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 ]
10 secondary outcomes
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
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
PK parameters will be calculated for rucaparib at steady-state
Time frame: Day 7-12
PK parameters will be calculated for rucaparib at steady-state
Time frame: Day 7-12
PK parameters will be calculated for rucaparib at steady-state
Time frame: Day 7-12
PK parameters will be calculated for rucaparib at steady-state
Time frame: Day 7-12
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
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2023.
- Derived from this study: PubMed 30427584Xiao 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Caffeine, Warfarin and Omeprazole in people with Neoplasms, run by pharmaand GmbH at 3 sites in Poland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02740712, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2023.