Pharmacokinetic Study to Evaluate Dabigatran Etexilate in Elderly Subjects

Health, Subjective Clinical Trial

Official title:

A Study Evaluating the Pharmacokinetics of Dabigatran Etexilate in Adult Healthy Subjects, Elderly Healthy Subjects, and Elderly Patients With Atrial Fibrillation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05715658
• Other study ID #: M2022280
• Status: Recruiting
• Phase: N/A
• Start date: August 15, 2022
• Est. completion date: July 30, 2023

Study information

• Verified date: February 2023
• Source: Peking University Third Hospital
• Contact: Dongyang Liu
• Phone: (86)010-82266658
• Email: liudongyang[@]vip.sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This study is a single-center, open-label clinical study, with adult healthy subjects, elderly healthy subjects and elderly patients with atrial fibrillation as the research subjects. 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. Blood samples at 0 h(before dosing), 2 h, 6 h, 10 h and 24 h after dosing, and additional stool samples were collected.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: July 30, 2023
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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.

2. 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).

3. 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.

4. Elderly patients with atrial fibrillation should have meet the diagnostic criteria for non-valvular atrial fibrillation.

5. Elderly patients with atrial fibrillation are taking Dabigatran etexilate for routine treatment.

Exclusion Criteria:

1. History of fainting of needles and blood.

2. 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.

3. Diseases affecting the activity of CYP3A in the liver: acute kidney injury, liver cirrhosis, liver abscess, liver cancer, intrahepatic bile duct stones, etc.

4. Diseases affecting changes in intestinal flora: non-alcoholic fatty liver disease, diabetes, chronic constipation.

5. History of major diseases or newly discovered diseases: prostate cancer, leukemia, liver cancer, breast cancer, colorectal cancer, leukemia and other tumor diseases.

6. 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.

7. Clinically significant active bleeding.

8. 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.

9. 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.

10. Use of drugs that may affect the activity of intestinal P-glycoprotein/CYP3A within 1 week before the trial: ? 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; ? Potent P-glycoprotein/CYP3A inducers: rifampicin, carbamazepine, phenytoin, phenobarbital, dexamethasone, antiandrogens (enzalutamide, apalutamide).

11. 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%)).

12. History of gastrointestinal surgery such as gallbladder or appendectomy, bariatric surgery, etc. within the past 6 months.

13. 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.

14. 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).

15. Subjects who are considered by the investigator to have any factors that are not suitable for participating in this trial.

Adult healthy subjects, with the following additional exclusion criteria:

16. Pregnant and lactating women.

17. Suffering from atrial fibrillation, hypertension, heart failure, coronary heart disease, heart valve disease and other diseases.

Related Conditions & MeSH terms

• Atrial Fibrillation
• Health, Subjective
• Nonvalvular Atrial Fibrillation

Intervention

Drug:
• Dabigatran etexilate capsule
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.

Locations

Country	Name	City	State
China	Peking University Third Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Dongyang Liu

Country where clinical trial is conducted

China, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Species of intestinal flora	Bacterial composition will be measured by 16s or Metagenome	on the first 1 day before administration
Secondary	Gene polymorphsim	Gene polymorphisms of CES1, CES2, P-glycolprotein will be measured	on the first 1 day before administration