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Determining the Clinical Relevance of the Interaction Between Enzalutamide and the Opioid Morphine and the DOAC Edoxaban

NCT05339672 · Status: UNKNOWN · Type: OBSERVATIONAL · Enrollment: 26

Last updated 2022-10-27

No results posted yet for this study

Summary

Enzalutamide is one of the oncolytic drugs that showed efficacy and safety in most of the features of prostate cancer. Approximately 17% of the patients treated with enzalutamide need pain control. Nearly all opioids are metabolized through one of the CYP enzymes induced by enzalutamide, making optimal pain management difficult. For pain control, while using enzalutamide, morphine is being advised since morphine is mainly glucuronidated by UGT2B7 and to a lesser extent UGT1A1. Enzalutamide is in vitro an inducer of UGT1A1 and may inhibit UGT2B7 which could alter morphine concentrations, though the clinical relevance of this interaction is unknown.

In patients with cancer, Direct Oral Anticoagulants (DOACs) are frequently used since vitamin-K antagonists were reported less effective than DOACs in preventing thromboembolic events. However, DOACs are all metabolized through CYP3A4 or P-gp. Due to interaction potential with DOACs, patients treated with enzalutamide are switched to Low Molecular Weight Heparin (LMWHs) administered subcutaneously which is considered safe but less patient friendly. For patients comfort DOACs are preferred over the use of LMWHs. Since rivaroxaban and apixaban are both major substrates for CYP3A4, combination with enzalutamide is prohibited. Dabigatran is a DOAC which is only metabolized by P-gp and edoxaban is a minor substrate for CYP3A4. Therefore, both might be safe to combine with enzalutamide. However, in patients with an active malignancy edoxaban is preferred according to national guidelines. Still, it is unknown if enzalutamide has a significant effect on the edoxaban exposure.

The purpose of this study is to evaluate the effect of enzalutamide on morphine and edoxaban pharmacokinetics.

Conditions

  • Drug-drug Interaction

Interventions

OTHER

Blood sampling - Pharmacokinetic assessment

Two pharmacokinetic assessements will be performed (before start of enzalutamide and 4-6 weeks after start of enzalutamide). Each pharmacokinetic assessment consists of 9 samples (3mL blood)

Sponsors & Collaborators

  • Astellas Pharma Inc

    collaborator INDUSTRY

  • Radboud University Medical Center

    lead OTHER

Eligibility

Min Age
18 Years
Sex
MALE
Healthy Volunteers
No

Timeline & Regulatory

Start
2024-07-01
Primary Completion
2024-08-31
Completion
2024-08-31

Countries

  • Netherlands

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05339672 on ClinicalTrials.gov