E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
If there are increased plasma levels of edoxaban when used concomitantly with the P-glycoproteïne inhibitor tamoxifen for the treatment of venous thromboembolism in patients with breast cancer. |
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E.1.1.1 | Medical condition in easily understood language |
If the amount of the blood thinner edoxaban in the blood increases while used simoultaneously with the hormonal treatment tamoxifen in patients with breast cancer who have thrombosis |
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E.1.1.2 | Therapeutic area | Body processes [G] - Chemical Phenomena [G02] |
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 compare the plasma concentration of edoxaban in women with breast cancer before and during treatment with tamoxifen. |
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E.2.2 | Secondary objectives of the trial |
To compare several coagulation, pharmacokinetic, and -dynamic parameters of edoxaban in women with breast cancer before and during treatment with tamoxifen. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age > 18 years - Patients with oestrogen receptor positive breast cancer who are scheduled for adjuvant or palliative tamoxifen treatment
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E.4 | Principal exclusion criteria |
- Inability to provide informed consent - Inherited bleeding disorder (e.g. von Willebrand disease) - Major bleeding16 or clinically relevant non-major bleeding17 in the past 3 months (see appendix A) - History of intracranial bleeding - Gastric or duodenal ulcer in the past 5 years - Uncontrolled blood pressure with systolic pressure >180 mmHg - Use of antiplatelet or anticoagulant therapy - Chronic NSAID use - Major surgery in the past 3 weeks (surgery which penetrates and exposes a body cavity or produces substantial impairment of physical function) - Pregnancy, puerperium, or current breast feeding - Use of strong P-gp inhibitors or inducers (see appendix B) - Brain metastases - Use of chemotherapy in the past 7 days or in the upcoming 32 days - AST or ALT >3x of the upper limit in the past 7 days - Liver cirrhosis Child Pugh A, B, or C - Creatinine clearance of <50mL/min calculated with the Cockcroft and Gault formula in the past 7 days - Body weight <60kg - Platelet count <50,000/mL in the past 7 days
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E.5 End points |
E.5.1 | Primary end point(s) |
a comparison between day 4 and 36 of edoxaban area under the plasma concenctration curve (AUC),maximum concentration (Cmax) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After two periods of 4 days of edoxaban use, the first without tamoxifen (last day: day 4) and the second with tamoxifen (last day: day 36). With a period of 28 days in between for tamoxifen to reach steady-state. |
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E.5.2 | Secondary end point(s) |
Anti-factor Xa activity calibrated for edoxaban, PT, aPTT and thrombin generation on day 4 and day 36. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After two periods of 4 days of edoxaban use, the first without tamoxifen (last day: day 4) and the second with tamoxifen (last day: day 36). With a period of 28 days in between for tamoxifen to reach steady-state. |
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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 | Yes |
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 | Yes |
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 |
Edoxaban alone is compared to edoxaban with concomitant use of tamoxifen |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |