E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prostate cancer |
Prostaatkanker |
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E.1.1.1 | Medical condition in easily understood language |
Prostate cancer |
Prostaatkanker |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- To determine the change in edoxaban and M4 exposure (AUC0-24hr) after start of enzalutamide or after discontinuation of enzalutamide - To determine the change in morphine and morphine-6-glucuronide exposure (AUC0-12hr) after start of enzalutamide or after discontinuation of enzalutamide
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E.2.2 | Secondary objectives of the trial |
- To evaluate the pain control (with the Numeric Rating Scale) in patients treated with and without enzalutamide and morphine - To 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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male patients with prostate cancer who will start treatment with enzalutamide within label or who will discontinue enzalutamide according to local guidelines - Patient 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 - 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
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E.4 | Principal exclusion criteria |
- Patients who are co-treated with drugs that could interfere with the metabolism of enzalutamide, edoxaban and/or morphine |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary aim is to show that there is: - no clinically relevant interaction between enzalutamide and morphine. A non-clinically relevant interaction is defined as 90 percent of the confidence intervals of the geometric mean ratio (GMR) of the morphine exposure (AUC0-12hr) falls within the range of 0.5-2.0.
- and no clinically relevant interaction between enzalutamide and edoxaban. A non-clinically relevant interaction is defined as 90 percent of the confidence intervals of the geometric mean ratio (GMR) of the edoxaban exposure (AUC0-24hr) falls within the range of 0.8-1.25.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Pharmacokinetic assessment will be done at 2 occasions (before start of enzalutamide: baseline and after 4 to 6 weeks of combination therapy or already on treatment of enzalutamide: baseline and after 8 weeks of discontinuation of enzalutamide therapy). |
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E.5.2 | Secondary end point(s) |
1. Pain control will be evaluated in patient treated with and without enzalutamide and morphine. The Numeric Rating scale will be filled in prior to start of enzalutamide and 1 month after start of enzalutamide or on treatment with enzalutamide and 8 weeks after discontinuation of enalutamide (during both visits for PK assessment). 2. Adverse events will be monitored and scored according to the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 to describe the safety of the combination of enzalutamide with edoxaban and/or morphine.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Before start of enzalutamide : baseline and after 4 to 6 weeks of combination therapy. Discontinuation of enzalutamide: baseline and 8 weeks after discontinuation of enzalutamide |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Patients are their own comparator: morhpine or edoxaban, with and without enzalutamide |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
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E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |