Population Pharmacokinetic Study of the Effect of Polymorphisms in the ABCB1 and CES1 Genes on the Pharmacokinetics of Dabigatran

According to published studies, the effects of genetic polymorphisms in the ABCB1 and CES1 genes on the blood concentration of dabigatran are controversial, and it is not clear whether dabigatran dosage and dosing intervals need to be adjusted according to genotype or other covariates in Chinese subjects. For these purposes, we will include patient demographics, genetic polymorphisms, and PK data based on a population pharmacokinetic study of dabigatran ester in healthy Chinese subjects to analyze the effect on dabigatran pharmacokinetics.

The aim of this study was to develop a population pharmacokinetic model to understand the relationship between dabigatran-related genes and dabigatran plasma levels after a single oral dose in healthy Chinese subjects and patients, and to analyze the effects of genetic variation on the efficacy and safety of dabigatran etexilate.

Study Overview

• Status: Not yet recruiting
• Conditions: Combined Analysis of Polymorphisms and Dabigatran Pharmacokinetic Parameters
• Intervention / Treatment: Drug: Dabigatran Etexilate 150mg

• Study Type: Observational
• Enrollment (Estimated): 30

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Healthy subjects in the dabigatran etexilate bioequivalence study; patients with nonvalvular atrial fibrillation (NVAF).

Description

Inclusion and exclusion criteria for healthy subjects were consistent with bioequivalence studies.

Inclusion Criteria:

1. Age 18-89 years;
2. ECG meeting the diagnostic criteria for atrial fibrillation;
3. Provide at least one valid blood sample for SNP testing;
4. no contraindication to anticoagulation, blood counts and coagulation times within normal reference values, and negative urine and stool occult blood;
5. not have had any stroke in the 6 months prior to enrollment.

Exclusion Criteria:

1. Cardiac ultrasound suggestive of moderate-to-severe mitral stenosis or after mechanical valve replacement;
2. severe hepatic injury or renal insufficiency (estimated glomerular filtration rate [eGFR] <30 mL/(min*1.73m2))
3. History of stroke or peripheral arterial embolism during dosing;
4. patients at high risk of bleeding, such as history of bleeding, hematologic disorders, other disorders requiring anticoagulant therapy, peptic ulcer and other bleeding, and blood pressure >180/110 mmHg;
5. Combination of other serious diseases, such as malignant tumors, severe hepatic and renal insufficiency;
6. history of allergy to dabigatran and warfarin.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma drug concentration	Blood samples collected 10-16 hours after the previous dose were considered trough plasma levels of dabigatran, and blood samples collected 1-3 hours after the dose were considered peak plasma levels.	3 day

Collaborators and Investigators

• Sponsor: The Affiliated Hospital Of Guizhou Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): June 10, 2025
• Study Completion (Estimated): November 25, 2025

Study Registration Dates

• First Submitted: April 24, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Dabigatran
• Other Study ID Numbers: 2024037K

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No