Edoxaban Steady-State PK/PD in Adults With Nephrotic Syndrome

Official title

Steady-state Pharmacokinetics and Pharmacodynamics of Edoxaban in Adults With Nephrotic Syndrome: A Non-randomized Open-label, Parallel Arm and Single-center Study

Overview

A study to evaluate the impact of nephrotic syndrome on the steady state pharmacokinetics and pharmacodynamics of edoxaban compared to health volunteers, and whether edoxaban can provide an equivalent anticoagulant effect to enoxaparin sodium.

Interventions

• Drug Edoxaban 60 mg
  film-coated tablet, manufactured by Daiichi Sankyo Europe GmbH
• Drug Enoxaparin 40 mg
  enoxaparin sodium, prefilled syringe of 0.4mL injectable solution, manufactured by SANOFI WINTHROP INDUSTRIE

Primary outcome measures

• area under the steady-state plasma concentration-time curve (AUCss) [Time frame: Day 4 post-administation]
• time to peak (Tmax) [Time frame: Day 4 post-administation]
• trough concentration at steady state (Css_min) [Time frame: Day 4 post-administation]
• peak concentration at steady state (Css_max) [Time frame: Day 4 post-administation]
• elimination half-life (t1/2) [Time frame: Day 4 post-administation]
• average steady-state plasma concentration (Css_av) [Time frame: Day 4 post-administation]]
• apparent volume of distribution (Vd/F) [Time frame: Day 4 post-administation]
• clearance (CL/F) [Time frame: Day 4 post-administation]
• anti-FXa activity [Time frame: Day 4 post-administation]
• prothrombin time (PT) [Time frame: Day 4 post-administation]

Eligibility criteria

Inclusion criteria

• Nephrotic syndrome Group:

• Age between 18-70 years old
• Diagnosed with nephrotic syndrome: proteinuria≥3.5 g/24h or morning urine protein/creatinine ratio ≥3.0g/g), with serum albumin <30g/L present at the time of enrollment, with or without edema or hyperlipidemia
• Calculated creatinine clearance (CrCl) >50ml/min using the Cockcroft-Gault formula
• Actual body weight >60kg, and body mass index within the range of 18.5-28kg/m2
• Signed informed consent form
• Healthy volunteer Group:

• Age between 18-70 years old
• Serum albumin ≥40g/L
• Calculated CrCl >50ml/min using the Cockcroft-Gault formula
• Actual body weight >60kg, and body mass index within the range of 18.5-28kg/m2
• Signed informed consent form

Exclusion criteria

• Serun albumin <30 g/L for other reasons in patients with nephrotic syndrome as judged by the investigator
• Prolonged PT, INR, APTT at baseline (defined as greater than the upper limit of normal values)
• Platelet count <100×109/L or ≥300×109/L due to hematological diseases confirmed by laboratory tests
• History of: gastrointestinal bleeding, intracranial hemorrhage, hemoptysis, or other clinically documented bleeding from internal organs within the last 3 months; surgery (except >3 days after renal biopsy without bleeding complications) or trauma. Bleeding complications after renal biopsy are defined as: ① bleeding (hematuria, perirenal hematoma, or arteriovenous fistula) that occur after renal biopsy requiring transfusion, resulting in altered hemodynamics, or requiring surgery or interventional treatment; ② symptomatic perirenal hematoma; and ③visible hematuria that persist for >3 days postoperatively.
• A lesion or condition with a significant risk of major bleeding, such as current or recent gastrointestinal ulcer, malignant tumors with a high risk of bleeding, esophageal varices, arteriovenous malformations, vascular aneurysms, or major intravertebral or intracerebral vascular malformations.
• Serious bleeding disorders as judged by the investigator
• Systemic lupus erythematosus with or without renal damage
• Bleeding or thrombophilia disorders as judged by the investigator
• History of stroke
• History of congestive heart failure (New York grade II or above) at the time of screening
• Liver dysfunction (cirrhosis or bilirubin >2×, and serum transaminases >3×, upper limit of normal)
• Use of (but not limited to) the prescription medications that are inhibitors or inducers of CYP3A4 and/or P-gp within the past 14 days:

• CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenytoin, etc.) ②CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, clarithromycin, etc.)

• P-gp inducers (e.g., apalutamide, rifampicin, etc.) ④ P-gp inhibitors (e.g., dronedarone, cyclosporine, erythromycin, ketoconazole, quinidine, verapamil, amiodarone, etc.) ⑤Selective serotonin reuptake inhibitors (SSRI) or serotonin-norepinephrine reuptake inhibitors (SNRI)
• Use of antiplatelet and/ or anticoagulant agents within 5 half-lives (at least 7 days): including but not limited to heparin, heparin derivatives, aspirin, clopidogrel, prasugrel, nonsteroidal anti-inflammatory drugs, warfarin, rivaroxaban, dabigatran, apixaban, etc.
• Pregnant or breastfeeding women or women of childbearing age without contraception
• Uncontrolled severe hypertension (SBP≥180mmHg, DBP≥110mmHg)
• Conditions considered unsuitable for inclusion in this study, judged by investigator
• Patients with hypersensitivity to the active ingredient or other excipients of the Edoxaban and enoxaparin sodium
• History of immune-mediated heparin-induced thrombocytopenia (HIT) or presence of circulating antibodies within the previous 100 days.
• Spinal or epidural anesthesia or local anesthesia within 24 hours prior to the administration of enoxaparin sodium and Edoxaban

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07116239 · 2025-h009

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗