Pharmacokinetics of edoxaban in patients with advanced chronic kidney disease (CKD) treated for stroke preventio

Phase 1

Conditions: onvalvular Atrial Fibrillation
MedDRA version: 20.0Level: PTClassification code 10003658Term: Atrial fibrillationSystem Organ Class: 10007541 - Cardiac disorders
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2019-003100-13-DE

Lead Sponsor: Martin-Luther-Universität Halle-Wittenberg

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 72

Inclusion Criteria

- Male and female patients aged 18 - 89 years
- Non-valvular atrial fibrillation
- Indication for initiation of oral anticoagulation therapy
- Cockcroft-Gault CreaCl 15 ml/min or higher
- CHA2DS2-VASc risk score = 2 (men) or = 3 (women)
- hospitalisation for reasons other than mere participation in this study
- Body weight from =60 kg to =125 kg during screening
- Written informed consent
- For women of childbearing potential: consent to the use of highly effective contraception (Pearl Index < 1)
- For men: consent to the use of condom as an additional contraception
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 24
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 48

Exclusion Criteria

- Cockcroft-Gault CreaCl < 15ml/min, unstable kidney function and/or need for renal replacement therapy
- Presence of a functional kidney transplant
- Known hypersensitivity to the active substance or to any of the excipients of the investigational medicinal product
- Clinically relevant, active bleeding
- Hepatic Disease associated with coagulopathy and clinically relevant bleeding risk
- Liver cirrhosis Child-Pugh stage C
- lesion or condition that may put the patient at significant risk for major bleeding, including but not limited to:
-Acute or recent (< 1 month) gastrointestinal ulceration,
-Malignant neoplasms at high risk of bleeding,
-Recent (< 1 month) brain or spinal injuries,
-Recent (< 1 month) brain, spinal or ophthalmic surgery,
-Recent (< 1 month) intracranial hemorrhage,
-Known or suspected esophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities
- Uncontrolled, severe arterial hypertension
- Current use (up to 7 days before screening) of NOAC or VKA
- Simultaneous systemic use of heparin or its derivatives (UFH, low molecular weight heparins, Fondaparinux, etc.) except under special circumstances of switching to oral anticoagulant therapy or when UFH is given at doses necessary to maintain an open central venous or arterial catheter
- Simultaneous systemic use of NSAIDs
- Pregnancy and lactation
- Co-treatment with one of the P-glycoprotein inhibitors Ciclosporin, Dronedarone, Erythromycin, Ketoconazole within the last 14 days, except for topical use
- Co-treatment with one of the P-glycoprotein inducers Apalutamid, Carbamazepin, Enzalutamid, Johanniskraut, Letermovir, Phenobarbital, Phenytoin, Pitolisant, Rifampicin within the last 14 days
- Inability to understand study procedures and to give informed consent
- Persons who due to judicial or administrative
arrangement are housed in an institution
- Simultaneous participation in another interventional study

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to analyse the pharmacokinetics (PK) of Edoxaban with reduced dose (30 mg once daily) in CKD patients with Cockcroft-Gault CreaCl 15 - 29 ml/min (group 1) and CKD patients with Cockcroft-Gault CreaCl 30 - 49 ml/min (group 2, experimental groups) each compared to normal dose (60 mg once daily) in patients with Cockcroft-Gault CreaCl = 50 ml/min (group 3, control group).;Secondary Objective: The secondary objective is to investigate the safety profile of the therapy, regarding (Serious) Adverse events.;Primary end point(s): Edoxaban AUC0-24 in steady-state (visit 3)<br><br>The visit 3 can already take place from day 5 for patients in group 2 (CreaCl 30 - 49 ml/min) and from day 4 for patients in group 3 (CreaCl = 50 ml/min).;Timepoint(s) of evaluation of this end point: Day 6 of study therapy<br><br>Optional: from day 5 for patients in group 2 (CreaCl 30 - 49 ml/min) and from day 4 for patients in group 3 (CreaCl = 50 ml/min)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Pharmacokinetic parameters of Edoxaban and the active M4 metabolites<br>- Adverse Events, Serious Adverse Events, Bleeding Events<br>;Timepoint(s) of evaluation of this end point: - Day 1 (visit 1), 6 (visit 3, optional for group 2 from day 5 and for group 3 grom day 4) and 14 (visit 4): pharmacokinetic parameters of Edoxaban and the active M4 metabolites<br>- Throughout the entire study therapy, day 1 to 14: adverse events, serious adverse events, bleeding events

Related Trials