Exploratory Drug Interaction Study Between SMIs and DOACs
Study Details
Study Description
Brief Summary
The main objective of this study is to investigate the effect of small molecule inhibitors (SMIs), used in targeted therapy for tumours, on direct oral anticoagulants (DOACs).
Condition or Disease | Intervention/Treatment | Phase |
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Detailed Description
Patients who receive anticoagulant therapy in the form of a direct oral anticoagulant (DOAC) and simultaneously receive anti-cancer targeted therapy with a small molecule inhibitor (SMI), potentially have an increased risk on thromboembolic complications and bleeding events due to interfering drug-drug interactions. Some SMIs influence CYP3A4 and/or p-glycoprotein (p-gp) for which DOACs are substrates. In this study, the effect of theoretically relevant SMIs on the pharmacokinetics, efficacy and safety of DOACs in patients with solid tumours will be investigated. For this purpose, plasma concentration analyses will be performed.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Group 1 Patients in group 1 already receive a DOAC and will start treatement with an SMI. Blood samples will be drawn before start of the SMI and during concomittant use with the SMI. |
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Group 2 Patients in group 2 already use a potentially relevant DOAC-SMI combination or already use an SMI and start with a DOAC. In this group, blood samples are taken after the start of concomittant use of the DOAC-SMI combination. |
Outcome Measures
Primary Outcome Measures
- DOAC trough concentration [At least 7 days after start DOAC use and in combination with an SMI at steady-state (after at least 21 days)]
DOAC trough concentration before and during concomitant use with an SMI
- DOAC peak concentration [At least 7 days after start DOAC use and in combination with an SMI at steady-state (after at least 21 days)]
DOAC peak concentration before and during concomitant use with an SMI
Secondary Outcome Measures
- Thromboembolic and bleeding events during follow-up [within 6 months after the last blood sampling]
Thromboembolic and bleeding events during follow-up
- SMI trough concentration during concomitant use with a DOAC [After the start of the DOAC use in combination with an SMI at steady-state (after at least 21 days)]
SMI steady-state trough concentration during concomintant use with a DOAC
Other Outcome Measures
- Thrombin generation before and during concomitant use of a DOAC and an SMI [At least 7 days after start DOAC use and in combination with an SMI at steady-state (after at least 21 days)]
Thrombin generation before and during concomitant use of a DOAC and an SMI
Eligibility Criteria
Criteria
Inclusion Criteria:
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Diagnosed with a solid tumour
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18 years of age or older
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Patients receive or start treatment with an SMI-DOAC combination, that may cause a clinically significant DDI at the level of CYP3A4 and/or P-gp, based on the SmPC
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Combined use of a DOAC-SMI combination is expected to be continued at the same dose for at least three weeks
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The DOAC is used for at least seven days and the SMI has already been used for at least 21 days at time of blood collection to ensure steady-state
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Patients receive a DOAC at maintenance dose
Exclusion Criteria:
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Unable to understand the information in the patient information letter
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Any concurrent medication beside the SMI and DOAC that is known to strongly inhibit or induce CYP3A4 or P-gp
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Patients who are pregnant or lactating
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Radboud UMC | Nijmegen | Gelderland | Netherlands | 6500HB |
2 | Maastricht UMC | Maastricht | Limburg | Netherlands | 6202AZ |
Sponsors and Collaborators
- Maastricht University Medical Center
- Radboud University Medical Center
Investigators
- Principal Investigator: Robin van Geel, PharMD, PhD, Maastricht UMC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NL78003.068.21