E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
theoretically none (PK study), but drug is used for prevention or treatment of VTE |
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E.1.1.1 | Medical condition in easily understood language |
prevention and treatment of blood clots |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
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 investigate the difference in peak level (Cmax) of apixaban between patients with and without SBS requiring long-term PN |
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E.2.2 | Secondary objectives of the trial |
- To investigate the difference in estimated trough level (Cmin), time to reach the peak level (Tmax) and area under the time to concentration curve (AUC) between patients with and without SBS requiring long-term PN - To investigate the difference in primary and secondary PK parameters (absorption rate constant, bioavailiability, volume of distribution, clearance and half-life) between patients with and without SBS requiring long-term PN - To describe the population PK and to quantify the impact of SBS on the PK of apixaban |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- arm A (anticoagulation naive short bowel syndrome patients): - patients with SBS (small bowel length of <2m after Treitz ligament) on long term (>3 months) PN or fluids who are anticoagulation naive - informed consent has to be signed - Arm B (patients with normal gastrointestinal tract starting on apixaban treatment): - patients without history of GI resections or other conditions associated with impaired absorption (= controls), who are anticoagulation naive and have to start anticoagulation for non-valvular AF with apixaban 2,5 mg or 5 mg twice daily (depending on patient characteristics cfr. 3.4.) - informed consent has to be signed |
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E.4 | Principal exclusion criteria |
- <18 years - non-Dutch speaking - recent (<6 months) GI surgery (only for arm A) - GI mucosal disease interfering with absorption (e.g. radio-enteritis, inflammatory bowel disease, celiac disease, …) (only for arm A) - GI fistulae (only for arm A) - SBS with intestinal failure resulting from gastric bypass surgery (only for arm A) - recent (<6 months) major bleeds according with the International Society on Thrombosis and Haemostasis definition of major bleeding in non-surgical patients (20) - creatinine clearance of < 15 mL/min or dialysis dependent - liver failure classified as Child Pugh C - total bilirubin ≥ 1.77 mg/dL (= 1,5 x upper limit of normal) - presence of coagulopathy and a clinically relevant bleeding risk - pregnancy or lactation - concomitant intake of other anticoagulant agents - concomitant intake of strong combined inhibitors of CYP3A4 and P-gp - participation in a recent (<3 months) trial with an investigational product |
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E.5 End points |
E.5.1 | Primary end point(s) |
To investigate the difference in peak level after two different single dose administrations (2,5 mg and 5 mg) of apixaban between patients with and without short bowel syndrome requiring long-term parenteral nutrition |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after sampling of the final patient |
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E.5.2 | Secondary end point(s) |
- To investigate differences in estimated trough level (12h after administration), time to reach peak level and area under the curve (AUC0-12) after two different single dose administrations (2,5 mg and 5 mg) of apixaban between patients with and without short bowel syndrome requiring long-term parenteral nutrition - To investigate the difference in absorption rate constant, bioavailiability, volume of distribution, clearance and half-life between patients with and without short bowel syndrome requiring long-term parenteral nutrition - To perform in silico investigation of optimised dosing schemes taking into account explained interindividual variability (ie, group dosing based on identified covariates) and unexplained interindividual variability (ie, precision dosing based on pharmacokinetics measurements |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
after sampling of the final patient |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
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 |
control group = patients with normal gastrointestinal tract |
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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
| 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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |