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

NCT07116239 | Not Yet Recruiting

• 1 other identifier: 2025-h009
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Nephrotic Syndrome; Hypoalbuminemia

Keywords

edoxaban; nephrotic syndrome; hypoalbuminemia; enoxaparin

Outcome Measures

Primary Outcomes (15)

• area under the steady-state plasma concentration-time curve (AUCss)

  ① Steady-state PK parameters of edoxaban in nephrotic syndrome patients versus healthy volunteers: area under the steady-state plasma concentration-time curve (AUCss)

  Day 4 post-administation

• time to peak (Tmax)

  Steady-state PK parameters of edoxaban in nephrotic syndrome patients versus healthy volunteers: time to peak (Tmax)

  Day 4 post-administation

• trough concentration at steady state (Css_min)

  Steady-state PK parameters of edoxaban in nephrotic syndrome patients versus healthy volunteers: trough concentration at steady state (Css\_min)

  Day 4 post-administation

• peak concentration at steady state (Css_max)

  Steady-state PK parameters of edoxaban in nephrotic syndrome patients versus healthy volunteers: peak concentration at steady state (Css\_max)

  Day 4 post-administation

• elimination half-life (t1/2)

  Steady-state PK parameters of edoxaban in nephrotic syndrome patients versus healthy volunteers: elimination half-life (t1/2)

  Day 4 post-administation

• average steady-state plasma concentration (Css_av)

  Steady-state PK parameters of edoxaban in nephrotic syndrome patients versus healthy volunteers: average steady-state plasma concentration (Css\_av)

  Day 4 post-administation]

• apparent volume of distribution (Vd/F)

  Steady-state PK parameters of edoxaban in nephrotic syndrome patients versus healthy volunteers: apparent volume of distribution (Vd/F)

  Day 4 post-administation

• clearance (CL/F)

  Steady-state PK parameters of edoxaban in nephrotic syndrome patients versus healthy volunteers: clearance (CL/F)

  Day 4 post-administation

• anti-FXa activity

  Steady-state PD parameters of edoxaban versus enoxaparin in nephrotic syndrome patients: anti-FXa activity

  Day 4 post-administation

• prothrombin time (PT)

  Steady-state PD parameters of edoxaban versus enoxaparin in nephrotic syndrome patients: prothrombin time (PT)

  Day 4 post-administation

• activated partial thromboplastin time(APTT)

  Steady-state PD parameters of edoxaban versus enoxaparin in nephrotic syndrome patients: activated partial thromboplastin time(APTT)

  Day 4 post-administation

• antithrombin Ⅲ(AT-III)

  Steady-state PD parameters of edoxaban versus enoxaparin in nephrotic syndrome patients: antithrombin Ⅲ(AT-III)

  Day 4 post-administation

• Protein C

  Steady-state PD parameters of edoxaban versus enoxaparin in nephrotic syndrome patients: Protein C

  Day 4 post-administation

• Protein S

  Steady-state PD parameters of edoxaban versus enoxaparin in nephrotic syndrome patients: Protein S

  Day 4 post-administation

• D-Dimer

  Steady-state PD parameters of edoxaban versus enoxaparin in nephrotic syndrome patients: D-Dimer

  Day 4 post-administation

Other Outcomes (1)

• Safety Assessment

  from the date of informed consent form signature to day 8 post-administration

Study Arms (5)

Edoxaban NS Group 1

EXPERIMENTAL

Patients with mild hypoalbuminemia (serum albumin \>25g/L and \<30g/L), taking edoxaban 60mg orally once daily

Drug: Edoxaban 60 mg

Edoxaban NS Group 2

EXPERIMENTAL

Patients with severe hypoalbuminemia (serum albumin ≤25g/L), taking edoxaban 60mg orally once daily

Drug: Edoxaban 60 mg

LMWH NS Group 1

ACTIVE COMPARATOR

Patients with mild hypoalbuminemia (serum albumin \>25g/L and \<30g/L), injecting enoxaparin sodium 0.4ml subcutaneously once daily

Drug: Enoxaparin 40 mg

LMWH NS Group 2

ACTIVE COMPARATOR

Patients with severe hypoalbuminemia (serum albumin ≤25g/L), injecting enoxaparin sodium 0.4ml subcutaneously once daily

Drug: Enoxaparin 40 mg

Healthy Volunteer Group

OTHER

Healthy volunteers, taking edoxaban 60mg orally once daily

Drug: Edoxaban 60 mg

Interventions

Edoxaban 60 mg DRUG

film-coated tablet, manufactured by Daiichi Sankyo Europe GmbH

Also known as: LIXIANAN

Edoxaban NS Group 1; Edoxaban NS Group 2; Healthy Volunteer Group

Enoxaparin 40 mg DRUG

enoxaparin sodium, prefilled syringe of 0.4mL injectable solution, manufactured by SANOFI WINTHROP INDUSTRIE

Also known as: CLEXANE

LMWH NS Group 1; LMWH NS Group 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University People's Hospital: lead
• Chinese Academy of Medical Sciences, Fuwai Hospital: collaborator

MeSH Terms

Conditions

Nephrotic Syndrome; Hypoalbuminemia

Interventions

edoxaban; Enoxaparin

Condition Hierarchy (Ancestors)

Nephrosis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hypoproteinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2025
• First Posted: August 11, 2025
• Study Start: September 1, 2025
• Primary Completion: February 1, 2026
• Study Completion: February 1, 2026
• Last Updated: August 11, 2025

Record last verified: 2025-08