Pharmacokinetic Study to Evaluate Dabigatran Etexilate in Elderly Subjects

NCT05715658 | Unknown

• 1 other identifier: M2022280
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This study intends to collect blood samples of adult healthy subjects, elderly healthy subjects and elderly patients with atrial fibrillation after taking dabigatran etexilate for pharmacokinetics and other studies, aiming to reveal the effect of dabigatran etexilate in Chinese elderly population. Pharmacokinetic profile and biomarker concentration levels; fecal samples were collected for gut microbiota studies to further explore potential mechanisms. The results of the study may provide reference for the precision medicine of dabigatran etexilate and other drugs in the elderly population or the development of new clinical drugs.

Conditions

Nonvalvular Atrial Fibrillation; Health, Subjective

Keywords

dabigatran pharmacokinetics; P-glycoprotein; older adult

Outcome Measures

Primary Outcomes (3)

• Concentration in plasma of dabigatran on the first day before administration

  Plasma concentration of dabigatran will be measured by LC-MS/MS or HPLC

  on the first 1 day before administration

• Concentration in plasma of dabigatran on the 2, 6, 10, and 24 hours after administration

  Plasma concentration of dabigatran will be measured by LC-MS/MS or HPLC

  on the 2, 6, 10, and 24 hours after administration

• Species of intestinal flora

  Bacterial composition will be measured by 16s or Metagenome

  on the first 1 day before administration

Secondary Outcomes (1)

• Gene polymorphsim

  on the first 1 day before administration

Study Arms (1)

Evaluating the pharmacokinetics of dabigatran etexilate in elderly healthy subjects

EXPERIMENTAL

Adult healthy subjects and elderly healthy subjects only took one 110mg dabigatran etexilate capsule orally, and elderly patients with atrial fibrillation took dabigatran etexilate according to routine medical care.

Drug: Dabigatran etexilate capsule

Interventions

Dabigatran etexilate capsule DRUG

Adult healthy subjects and elderly healthy subjects only take one 110 mg dabigatran etexilate capsule (low-dose specification in the instruction manual) orally. Elderly patients with atrial fibrillation take dabigatran etexilate according to routine medical treatment.

Evaluating the pharmacokinetics of dabigatran etexilate in elderly healthy subjects

Eligibility Criteria

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

You may qualify if:

• With full capacity for civil conduct, the age of adult healthy subjects is ≥18 years old and ≤30 years old; elderly healthy subjects ≥ 75 years old; elderly patients with atrial fibrillation are ≥75 years old.
• Male weight ≥ 50 kg, female weight ≥ 45 kg; body mass index (BMI) within the range of 19.0\~27.0 (including upper and lower limits), body mass index (BMI) = weight (kg) / height 2 (m2).
• Creatinine clearance rate (CRCL): calculated by Cock Croft-Gault equation, adult healthy subjects should have CRCL≥90mL/min; elderly healthy subjects should have CRCL≥60mL/min; elderly patients with atrial fibrillation should have CRCL≥30mL/min.
• Elderly patients with atrial fibrillation should have meet the diagnostic criteria for non-valvular atrial fibrillation.
• Elderly patients with atrial fibrillation are taking Dabigatran etexilate for routine treatment.

You may not qualify if:

• History of fainting of needles and blood.
• Diseases affecting intestinal P-glycoprotein: severe diarrhea (excretion more than 3 times a day with watery stool characteristics), Crohn's disease, ulcerative colitis, irritable bowel syndrome, diverticulitis, difficult Identify Clostridium infection (recurrent) or Helicobacter pylori infection.
• Diseases affecting the activity of CYP3A in the liver: acute kidney injury, liver cirrhosis, liver abscess, liver cancer, intrahepatic bile duct stones, etc.
• Diseases affecting changes in intestinal flora: non-alcoholic fatty liver disease, diabetes, chronic constipation.
• History of major diseases or newly discovered diseases: prostate cancer, leukemia, liver cancer, breast cancer, colorectal cancer, leukemia and other tumor diseases.
• Diseases or conditions with significant risk of major bleeding, such as current or recent peptic ulcer, malignant neoplasms with high bleeding risk, recent brain or spinal cord injury, recent brain, spinal cord, or eye surgery, recent intracranial hemorrhage, known or suspected Esophageal varices, arteriovenous malformations, vascular aneurysms, or major intraspinal or intracranial vascular abnormalities.
• Clinically significant active bleeding.
• Are using anticoagulant drugs such as unfractionated heparin (UFH), low molecular weight heparin (LMWH) and heparin derivatives (fondaparinux sodium), vitamin K antagonists, rivaroxaban or other direct thrombin Inhibitors (recombinant hirudin, bivalirudin); thrombolytic drugs; or current use of antiplatelet aggregation drugs such as GPIIb/IIIa receptor antagonists, ticlopidine, prasugrel, dextran, sulfinpyrazone, aspirin, etc.
• Use of drugs that may affect the intestinal flora within 1 week before the trial: Continuous use of antibiotics, Bifidobacterium triple viable bacteria powder, lactobacillus tablets, compound Lactobacillus acidophilus tablets, Bacillus subtilis dual viable bacteria enteric-coated capsules, containing bismuth subsalicylate, etc.
• Use of drugs that may affect the activity of intestinal P-glycoprotein/CYP3A within 1 week before the trial: ① Potent P-glycoprotein/CYP3A inhibitors: amiodarone, verapamil, diltiazem, quinidine, dronedarone, tacrolimus, cyclosporine, protease inhibitors indinavir, nelfinavir, saquinavir, lopinavir), macrolide antibiotics (erythromycin, clarithromycin, telithromycin), chloramphenicol, azole Antifungal drugs (ketoconazole, itraconazole, Posaconazole, voriconazole, fluconazole, miconazole), nefazodone, cobicistat, cimetidine, ciprofloxacin, Imatinib, St. John's Wort, Ranolazine; ② Potent P-glycoprotein/CYP3A inducers: rifampicin, carbamazepine, phenytoin, phenobarbital, dexamethasone, antiandrogens (enzalutamide, apalutamide).
• Those who have a history of smoking and drinking in the past, and who do not agree with the prohibition of smoking and drinking during the trial period: smokers (the average daily cigarettes smoked more than 5 cigarettes within one month before the test); alcoholism (the average daily drinking within one month before the test) ≥100mL high-quality liquor (ethanol content ≥40%)).
• History of gastrointestinal surgery such as gallbladder or appendectomy, bariatric surgery, etc. within the past 6 months.
• Positive virological test (human immunodeficiency virus antibody (HIV-Ab), syphilis serological test, hepatitis B virus surface antigen (HBsAg) or hepatitis C virus antibody (HCV-Ab)) within 3 months before screening.
• Those who have participated in clinical trials of any drug or medical device within 1 month before screening (in the case of drug clinical trials, those who participated in the previous clinical trial before screening have more than 5 half-lives).
• Subjects who are considered by the investigator to have any factors that are not suitable for participating in this trial.

Sponsors & Collaborators

• Dongyang Liu: lead

Study Sites (1)

Peking University Third Hospital

Beijing, 100191, China

RECRUITING

Related Publications (3)

• Hines LE, Murphy JE. Potentially harmful drug-drug interactions in the elderly: a review. Am J Geriatr Pharmacother. 2011 Dec;9(6):364-77. doi: 10.1016/j.amjopharm.2011.10.004. Epub 2011 Nov 11.

  PMID: 22078863 RESULT

• Zorab PA. Proceedings: Prognosis for life in childhood scoliosis. Arch Dis Child. 1973 Oct;48(10):824-5. doi: 10.1136/adc.48.10.824-c. No abstract available.

  PMID: 4749689 RESULT

• Elmeliegy M, Vourvahis M, Guo C, Wang DD. Effect of P-glycoprotein (P-gp) Inducers on Exposure of P-gp Substrates: Review of Clinical Drug-Drug Interaction Studies. Clin Pharmacokinet. 2020 Jun;59(6):699-714. doi: 10.1007/s40262-020-00867-1.

  PMID: 32052379 RESULT

MeSH Terms

Interventions

Dabigatran

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Dongyang Liu

  Drug Clinical Trial Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dongyang Liu

CONTACT

(86)010-82266658; liudongyang@vip.sina.com

Cheng Cui

CONTACT

13011825605; cuicheng1226@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Vice director of Drug Clinical Center

Model Details: Control group: 12 healthy adults (18-30 years old); Test group A: 12 elderly healthy people (≥75 years old); Test group B: 12 elderly patients with atrial fibrillation (≥75 years old).

Study Record Dates

• First Submitted: July 4, 2022
• First Posted: February 8, 2023
• Study Start: August 15, 2022
• Primary Completion: June 30, 2023
• Study Completion: July 30, 2023
• Last Updated: February 8, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)