Population Pharmacokinetics of Edoxaban in Chinese Patients With Non-Valvular Atrial Fibrillation

Non-Valvular Atrial Fibrillation Clinical Trial

Official title:

Population Pharmacokinetics of Edoxaban in Chinese Patients With Non-Valvular Atrial Fibrillation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05320627
• Other study ID #: EPP-AF-102
• Status: Recruiting
• Phase: Phase 4
• Start date: March 30, 2022
• Est. completion date: December 30, 2024

Study information

• Verified date: March 2024
• Source: China National Center for Cardiovascular Diseases
• Contact: Lei Tian
• Phone: +861088398547
• Email: tianlei0807[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Based on the population pharmacokinetic data of Chinese patients with atrial fibrillation, the study will evaluate the suitability of the ENGAGE Population Pharmacokinetics model of edoxaban in patients with atrial fibrillation in China, and build a predictive dose model of edoxaban that meets the characteristics of Chinese people. It can provide perfect individualized dosing plan improves clinical efficacy and reduces adverse drug reactions.

Description:

This is an open label study. Male or female patients with non-valvular atrial fibrillation (NVAF) with age ≥20 years, and meeting the indications of edoxaban are potentially eligible for the study. Patients receive Edoxaban 15mg、30mg or 60mg according to the criteria as following:

1. Patients with severe renal insufficiency (15ml/min ≤ CrCl <30ml/min), 15mg quaque die (QD)

2. Patients with normal or mild renal insufficiency (CrCl ≥50ml/min), 60mg QD

3. Patients with moderate renal insufficiency (30ml/min ≤ CrCl <50ml/min), weight ≤60kg or combined use of P-gp inhibitors (such as dronedarone，ketoconazole, erythromycin, etc), 30mg QD.

Patients will receive clinical evaluation at screening period, 4 weeks、8 weeks and 12 weeks after administration with Edoxaban. The following clinical evaluation items were included: body weight, vital signs (blood pressure and heart rate), CHADS2-VAS score, concomitant medication, ECG and echocardiogram, laboratory examination, safety evaluation (thromboembolic events, bleeding events, death) during treatment.

Additional blood samples are collected for pharmacokinetic evaluation at screening period, pre-dose, 2±1h and 6±1h after administration at 4-, 8-, and 12-week visit, and for pharmacodynamic evaluation (FXa) at screening period, pre-dose after administration at 4-, 8-, 12-week visit.

The population pharmacokinetics of Edoxaban in Chinese patients with non-valvular atrial fibrillation will be determined after 12weeks clinical observation.

The ENGAGE PopPK model suitable in Chinese Patients with Non-Valvular Atrial Fibrillation will be established.

Safety outcomes (thromboembolic events, bleeding events, death) will be evaluated.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 30, 2024
• Est. primary completion date: August 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

1. Male or female NVAF patients, who need anticoagulant therapy at least 3 months

2. Age =20 years,

3. Creatinine clearance rate = 15 ml/min

4. Sign a written informed consent form (ICF) for participating in the study

5. No simultaneous participation in any interventional study

Exclusion Criteria:

1. Patients with the Valve replacement

2. Patients with valvular atrial fibrillation

3. Mild and severe anemia patients

4. CrCl<15ml/min

5. Patients on dialysis, risk of bleeding, taking antiplatelet drugs, or taking other anticoagulants

6. Contraindicated to Edoxaban.

7. Life expectancy < 6 months.

8. Hypertension defined as systolic and/or diastolic blood pressure > 95th age percentile or poorly controlled hypertension

9. Hepatic disease which is associated either: with coagulopathy leading to a clinically relevant bleeding risk, or alanine transaminase (ALT) > 5x upper level of normal (ULN), or total bilirubin > 2x ULN with direct bilirubin > 20% of the total.

10. Active bleeding or high risk for bleeding contraindicating anticoagulant therapy. For example:

• a history of intracranial, intraocular, intraspinal, retroperitoneal, or traumatic intra-articular bleeding

• gastrointestinal bleeding during the prior year

• peptic ulcer within the previous 90 days

• surgery or injury requiring hospitalization within the previous 30 days

• hemoglobin <9 g/dl or a platelet count <50×109/L

• active bleeding at registration

• any procedure associated with bleeding planned to occur during the treatment period

11. Urine pregnancy test positive if female

12. Inability to cooperate with the study procedures

13. Participation in a study with an investigational drug or medical device within 30 days prior to screening

14. Additional exclusion criteria included, but were not limited to:

• cerebral infarction or transient ischemic attack within the past 30 days

• comorbid rheumatic valvular disease

• comorbid infective endocarditis or atrial myxoma

• evidence of thrombus in the left ventricle or atrium, or hereditary tendency for thrombus formation scheduled electrical or pharmacological defibrillation during the treatment period

• acute myocardial infarction, or unstable angina

• a diagnosis of active malignant tumor or cancer treatment within the past 5 years

• previous treatment with Edoxaban

Related Conditions & MeSH terms

• Atrial Fibrillation
• Non-Valvular Atrial Fibrillation

Intervention

Drug:
• Edoxaban
Eligible patients will receive Edoxaban tablet once a day for 12 weeks

Locations

Country	Name	City	State
China	Fuwai Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
China National Center for Cardiovascular Diseases	Chinese Academy of Medical Sciences, Fuwai Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	population pharmacokinetic evaluation	Patients enrolled will be back to center for visit at scheduled timepoint. Blood sample for PopPK study was collected. Edoxaban concentrations in patient plasma will be determined, which will be analysed and compared with ENGAGE PopPK model.	at the 4th, 8th and 12th week
Primary	pharmacokinetic evaluation	Patients enrolled will be back to center for visit at scheduled timepoint. Blood for pharmacodynamic sample will be collected for Anti-FXa activity determination.	at the 4th, 8th and 12th week
Secondary	safety evaluation	Patients enrolled will be back to center for visit at scheduled timepoint. Adverse even will be recorded. The investigator will determine whether the patient is suitable to go on with the study.	at the 4th, 8th and 12th week