Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ended
Participants planned
40
Countries
1
Sites
4
Prostate cancer
To determine the change in edoxaban and M4 exposure (AUC0-24hr) with or without enzalutamide - To determine the change in morphine and morphine-6- glucuronide exposure (AUC0-12hr) with or without enzalutamide
Key facts
- Sponsor
- Radboud universitair medisch centrum Stichting
- Participant type
- Patients
- Age range
- 65+ years
- Gender
- Male
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 1 Feb 2023 → 15 Jul 2025
- Decision date (initial)
- 2024-11-15
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Astellas Pharma
External identifiers
- EU CT number
- 2024-517646-34-00
- EudraCT number
- 2022-001410-20
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacokinetic, Others
To determine the change in edoxaban and M4 exposure
(AUC0-24hr) with or without enzalutamide
- To determine the change in morphine and morphine-6-
glucuronide exposure (AUC0-12hr) with or without
enzalutamide
Secondary objectives 1
- If a patient also has a treatment indication with opioids for pain: To evaluate the pain control (with the Numeric Rating Scale) in patients treated with and without enzalutamide and morphineTo evaluate the safety of the combination of enzalutamide with edoxaban and/or morphine monitored with CTC-AE v 5.0 criteria. - To evaluate the effect of edoxaban and/or morphine on enzalutamide exposure
Conditions and MedDRA coding
Prostate cancer
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- Patient with prostate cancer - Patients who will start treatment with enzalutamide within label or are on treatment with enzalutamide AND are on treatment with edoxaban (30mg or 60mg OD, according to the label) (edoxaban arm 1) OR are on treatment with morphine IR or other opioids IR and willing and able to switch to morphine IR or not treated with opioids and willing and able to receive morphine (a single-dose of 10 mg immediate-release (group 1)) or are on treatment with morphine XR or other opioids XR and able to switch to morphine XR BID (group 2)) (morphine arm 3) OR - Patients that are on treatment with edoxaban (30 or 60mg OD, according to the label) (edoxaban arm 2) OR are on treatment with morphine IR or other opioids IR and willing and able to switch to morphine IR or not treated with opioids and willing and able to receive morphine (a singledose of 10 mg immediate-release (group 1) or are on treatment with morphine XR or other opioids XR and able to switch to morphine XR BID (group 2)) (morphine arm 4) - Age at least 18 years - Patient 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
Exclusion criteria 1
- Exclusion criteria: - Patients who are co-treated with drugs that could interfere with the metabolism of enzalutamide, edoxaban and/or morphine - For patients in morphine group 1: use of morphine rescue <12 hours prior to the PK assessment day - Patients requiring subcutaneous or intravenous opioid treatment - If hypersensitive to morphine - Patients suffering from diarrhea - If any type of liver function abnormality, such as active or symptomatic viral hepatitis or chronic liver disease or liver cirrhosis - Patients with respiratory depression - Hypercapnia - Patients with increased intracranial pressure or brain trauma - Patients with a history of bronchial asthma, chronic obstructive pulmonary disease or pulmonary heart disease - Patients with a history of abuse - Delirium tremens - Patients with anxiety or agitation with the use of alcohol of hypnotics - Patients with evidence of clinically significant gastrointestinal disease, such as ileus, biliary colic, peritonitis - Patients with previous gastric bypass or gastric band surgery - Patients with sickle cell anemia - Patient with major surgery within 1 month prior to screening - Patients with sleep apnea
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- To determine the change in edoxaban and M4 exposure (AUC0-24hr) with or without enzalutamide - To determine the change in morphine and morphine-6- glucuronide exposure (AUC0-12hr) with or without enzalutamide
Secondary endpoints 1
- If a patient also has a treatment indication with opioids for pain: To evaluate the pain control (with the Numeric Rating Scale) in patients treated with and without enzalutamide and morphineTo evaluate the safety of the combination of enzalutamide with edoxaban and/or morphine monitored with CTC-AE v 5.0 criteria. - To evaluate the effect of edoxaban and/or morphine on enzalutamide exposure
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 3
—
SCP1000773 · ATC
- Route of administration
- ORAL
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 400 mg milligram(s)
- Max treatment duration
- 1000 Month(s)
- Authorisation status
- Authorised
- ATC code
- N02AA01 — MORPHINE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP257594 · ATC
- Active substance
- Edoxaban
- Route of administration
- ORAL
- Max daily dose
- 60 mg milligram(s)
- Max total dose
- 60 mg milligram(s)
- Max treatment duration
- 1000 Month(s)
- Authorisation status
- Authorised
- ATC code
- B01AF03 — EDOXABAN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP104122323 · ATC
- Active substance
- Enzalutamide
- Substance synonyms
- MDV3100
- Route of administration
- ORAL
- Max daily dose
- 160 mg milligram(s)
- Max total dose
- 160 mg milligram(s)
- Max treatment duration
- 1000 Month(s)
- Authorisation status
- Authorised
- ATC code
- L02BB04 — ENZALUTAMIDE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Radboud universitair medisch centrum Stichting
- Sponsor organisation
- Radboud universitair medisch centrum Stichting
- Address
- Geert Grooteplein Zuid 10
- City
- Nijmegen
- Postcode
- 6525 GA
- Country
- Netherlands
Scientific contact point
- Organisation
- Radboud universitair medisch centrum Stichting
- Contact name
- Nienke Op 't Hoog
Public contact point
- Organisation
- Radboud universitair medisch centrum Stichting
- Contact name
- Nienke Op 't Hoog
Locations
1 EU/EEA country · 4 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ended | 40 | 4 |
| Rest of world | — | 0 | — |
Investigational sites
Deventer Ziekenhuis
Medical Oncology, Nico Bolkesteinlaan 75, 7416 SE, Deventer
Sint Franciscus Vlietland Groep Stichting
Medical Oncology, Kleiweg 500, 3045 PM, Rotterdam
Radboud universitair medisch centrum Stichting
Pharmacy, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen
Canisius Wilhelmina Ziekenhuis
Urology, Weg Door Jonkerbos 100, 6532 SZ, Nijmegen
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Netherlands | 2023-02-01 | 2025-07-15 | 2023-02-01 | 2025-07-15 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 12 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1 Protocol MIND THE GAP 2024-517646-34-00 redacted | 11 |
| Recruitment arrangements (for publication) | K1_blank_document_Recruitment_arrangements | 1 |
| Subject information and informed consent form (for publication) | L1 PIF MIND THE GAP edoxaban met enzalutamide redacted | 7.2 |
| Subject information and informed consent form (for publication) | L1 PIF MIND THE GAP edoxaban zonder enzalutamide redacted | 7.3 |
| Subject information and informed consent form (for publication) | L1 PIF MIND THE GAP morfine met enzalutamide_IR redacted | 9.1 |
| Subject information and informed consent form (for publication) | L1 PIF MIND THE GAP morfine met enzalutamide_XR redacted | 8.1 |
| Subject information and informed consent form (for publication) | L1 PIF MIND THE GAP morfine zonder enzalutamide_IR redacted | 9.2 |
| Subject information and informed consent form (for publication) | L1 PIF MIND THE GAP morfine zonder enzalutamide_XR redacted | 8.2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2 SPC edoxaban | N/A |
| Summary of Product Characteristics (SmPC) (for publication) | E2 SPC morphine IR | N/A |
| Summary of Product Characteristics (SmPC) (for publication) | E2 SPC morphine XR | N/A |
| Summary of Product Characteristics (SmPC) (for publication) | E2 SPX enzalutamide | N/A |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-03 | Netherlands | Acceptable 2024-11-15
|
2024-11-15 |