Drug-drug InteractionMIND THE GAPNCT05339672
Determining the Clinical Relevance of the Interaction Between Enzalutamide and the Opioid Morphine and the DOAC Edoxaban
An observational study of Drug-drug Interaction, run by Radboud University Medical Center at 3 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Drug-drug Interaction
- What is being tested?
- Blood sampling - Pharmacokinetic assessment
- How many people
- 26 participants
- Where
- 3 sitesNetherlands
- Study dates
- 1 Jul 2024to 31 Aug 2024
- Phase
- Observational
- 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
- Men only
- Adult, Older adult
Study population: Patients with prostate cancer starting enzalutamide therapy
Who may be able to join
- Patients with prostate cancer who will start treatment with enzalutamide within label
- Patients who are on treatment with opioids and/or therapeutic anticoagulation, that are treated with or willing and able to switch to morphine (2 dd extended release equivalent dose) and/or edoxaban (30mg or 60mg OD, according to the label)
- Age at least 18 years
- Patients who are able and willing to give written informed consent prior to screening
- Patients from whom it is possible to collect blood samples
- Life expectancy of > 3 months
- Stable renal function and renal clearance > 50ml/min
Who cannot join
- Patients who are co-treated with drugs that could interfere with the metabolism of enzalutamide, edoxaban and/or morphine
Trial locations and contacts
3 sites in 1 country.
Netherlands3 sites, 3 recruiting
- Not yet recruiting
Canisius Wilhelmina Ziekenhuis
Nijmegen
Rik Somford, MD,PhD
Rik Somford, MD, PhD
- Recruiting
Radboudumc
Nijmegen
Nielka van Erp, Dr.
Inge van Oort, Dr.
- Not yet recruiting
Franciscus Gasthuis en Vlietland hospital
Rotterdam
Paul Hamberg, Dr
About this study
Official title: Determining the Clinical Relevance of the Interaction Between Enzalutamide and the Opioid Morphine and the DOAC Edoxaban to Improve Rational Pharmacological Care of Patients With Prostate Cancer
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
- Being tested
- Blood sampling - Pharmacokinetic assessment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood sampling - Pharmacokinetic assessmentOther
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)
| Study group | Role | What they receive |
|---|---|---|
| Morphine | The participating patients are treated with morphine before start of enzalutamide (according to label). Receives: Other: Blood sampling - Pharmacokinetic assessment | |
| Edoxaban | The participating patients are treated with edoxaban before start of enzalutamide (according to label). Receives: Other: Blood sampling - Pharmacokinetic assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the change in morphine and morphine-6-glucuronide exposure
Change in AUC0-12hr
Measured: 4-6 weeks after start of enzalutamide
To determine the change in edoxaban and M4 exposure
Change in AUC0-24hr
Measured: 4-6 weeks after start of enzalutamide
Secondary outcomes (3)
To evaluate the pain control in patients treated with and without enzalutamide and morphine
Change in Numeric Rating Scale (NRS). The pain NRS is a single 11-point numeric scale, with 0 representing no pain and 10 representing extreme pain.
Measured: 4-6 weeks after start of enzalutamide
To evaluate the safety of the combination of enzalutamide with edoxaban and/or morphine
monitored with CTC-AE v 5.0 criteria.
Measured: 4-6 weeks after start of enzalutamide
To evaluate the effect of edoxaban and/or morphine on enzalutamide exposure
Change in Ctrough of enzalutamide
Measured: 4-6 weeks after start of enzalutamide
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2022
- Study start1 Jul 2024 (estimated)
- Primary completion31 Aug 2024 (estimated)
- Study completion31 Aug 2024 (estimated)
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 Drug-drug InteractionStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Case crossover
- Time perspective
- Prospective
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Astellas Pharma Inc
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05339672
- Sponsor's protocol ID
- MIND THE GAP
- Acronym
- MIND THE GAP
- Status last verified
- Apr 2022
- First submitted
- 14 Apr 2022
- Last updated
- 27 Oct 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Op 't Hoog CJP, Mehra N, van der Weij B, Olofsen E, Somford DM, van Oort IM, Hamberg P, van Erp NP, Boerrigter E. Effect of Enzalutamide on Morphine Exposure in Patients with Prostate Cancer. Clin Pharmacokinet. 2026 May;65(5):763-772. doi: 10.1007/s40262-026-01640-6. Epub 2026 May 4.
PubMed 42081083
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determining the Clinical Relevance of the Interaction Between Enzalutamide and the Opioid Morphine and the DOAC Edoxaban to Improve Rational Pharmacological Care of Patients With Prostate Cancer
- ClinicalTrials.gov ID
- NCT05339672
- Acronym / sponsor ID
- MIND THE GAP / MIND THE GAP
- Conditions
- Drug-drug Interaction
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Astellas Pharma Inc
- Study start
- 1 Jul 2024 (estimated)
- Primary completion
- 31 Aug 2024 (estimated)
- Study completion
- 31 Aug 2024 (estimated)
- First posted
- 21 Apr 2022 (actual)
- 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.
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.
Study design
- Observational model
- Case crossover
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Morphine | – | Other: Blood sampling - Pharmacokinetic assessmentThe participating patients are treated with morphine before start of enzalutamide (according to label). |
| Edoxaban | – | Other: Blood sampling - Pharmacokinetic assessmentThe participating patients are treated with edoxaban before start of enzalutamide (according to label). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Age groups
- Adult, Older adult
- Study population
- Patients with prostate cancer starting enzalutamide therapy
Key inclusion criteria (7 listed)
- Patients with prostate cancer who will start treatment with enzalutamide within label
- Patients who are on treatment with opioids and/or therapeutic anticoagulation, that are treated with or willing and able to switch to morphine (2 dd extended release equivalent dose) and/or edoxaban (30mg or 60mg OD, according to the label)
- Age at least 18 years
- Patients who are able and willing to give written informed consent prior to screening
- Patients from whom it is possible to collect blood samples
Key exclusion criteria (1 listed)
- Patients who are co-treated with drugs that could interfere with the metabolism of enzalutamide, edoxaban and/or morphine
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 |
|---|---|---|
| Blood sampling - Pharmacokinetic assessmentTwo 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) | Other | Edoxaban, Morphine |
Primary outcome
To determine the change in morphine and morphine-6-glucuronide exposure
Time frame: 4-6 weeks after start of enzalutamide
Change in AUC0-12hr
To determine the change in edoxaban and M4 exposure
Time frame: 4-6 weeks after start of enzalutamide
Change in AUC0-24hr
3 secondary outcomes
To evaluate the pain control in patients treated with and without enzalutamide and morphine
Time frame: 4-6 weeks after start of enzalutamide
To evaluate the safety of the combination of enzalutamide with edoxaban and/or morphine
Time frame: 4-6 weeks after start of enzalutamide
To evaluate the effect of edoxaban and/or morphine on enzalutamide exposure
Time frame: 4-6 weeks after start of enzalutamide
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2022.
- Derived from this study: PubMed 42081083Op 't Hoog CJP, Mehra N, van der Weij B, Olofsen E, Somford DM, van Oort IM, Hamberg P, van Erp NP, Boerrigter E. Effect of Enzalutamide on Morphine Exposure in Patients with Prostate Cancer. Clin Pharmacokinet. 2026 May;65(5):763-772. doi: 10.1007/s40262-026-01640-6. Epub 2026 May 4.
- 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.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Drug-drug Interaction, run by Radboud University Medical Center at 3 sites in Netherlands.
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 7 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 27 Oct 2022. 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 Netherlands. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Emmy Boerrigter, PharmD (+31631026328, emmy.boerrigter@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the change in morphine and morphine-6-glucuronide exposure (time frame: 4-6 weeks after start of enzalutamide). 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 NCT05339672, 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 27 Oct 2022.