Effect of Oral D-mannose Tablets on Pharmacokinetics of Dabigatranate in Healthy Adults

Health Clinical Trial

Official title:

A Prospective, Single-Center, Open-Label Study of the Effect of Oral D-mannose Tablets on the Pharmacokinetics of Dabigatran Etexilate in Healthy Adults

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06360055
• Other study ID #: M2024130
• Status: Recruiting
• Phase: N/A
• Start date: April 1, 2024
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2024
• 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

The aim of this study is to investigate the effects of oral D-mannose tablets for 2 consecutive weeks on the pharmacokinetics of dabigatrun etexilate, a P-glycoprotein probe substrate drug, in healthy adults

Description:

This study is a prospective, sinale-center, open-label clinical studly, with adult healthy subiects as the research subjects. Healthy adult subjects will receive a single oral dose of 110mg (low dose specification in the instructions) or lower of dabigatran etexilate on day 1 and day 16 of the trial period. Blood samples for dabigatran plasma concentration determination at 0 h(before dosing)2 h, 4 h, 6 h, 12 h and 24 h after dosing will be taken. Subjects will take 3g (1g*3 tablets) of D-mannose tablets every morning and evening from the 2nd day to the 15th day of the trial period, with a total of 6g/day (medium dose specification in the instructions). Blood samples for detection of glycotomic serum concentrations such as D-mannose will be taken 0h before oral administration of dabigatran etexilate on day 1 and 1.5h after oral administration of D-mannose each morning on days 2, 8, and 15 of the trial period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: December 31, 2024
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. With full capacity for civil conduct, the age of healthy male subjects is =18 years old and =45 years old

2. Male weight =50 kg; body mass index (BMI) within the range of 19.0~27.0 (including upper and lower limits)

3. Creatinine clearance rate (CRCL: calculated by Cock croft-Gault equation, adult healthy subjects should have CRCL=90mL/min

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. Diabetes mellitus; Impaired fasting glucose (IFG); Impaired glucose tolerance (IGT); Oral hypoglycemic agents (including the use of hypoglycemic agents for weight loss purposes).

4. 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.

5. Clinically significant active bleeding.

6. Taking anticoagulants 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 GP?b/?a receptor antagonists, ticlopidine, prasugrel, dextran, sulfinpyrazone, aspirin, etc.

7. Use of drugs that may affect the activity of intestinal p-glycoprotein within 1 week before the trial: (1) potent p-glycoprotein 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, cyclosporin, fluvoxamine, imatinib, St. John's Wort, ranolazine; (2) Potent P-glycoprotein inducers: rifampicin, carbamazepine, phenytoin, phenobarbital, antiandrogens(enzalutamide, apalutamide), phenobarbital, dexamethasone.

8. 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/200mL wine / 600mL beer).

9. History of gastrointestinal surgery such as gallbladder or appendectomy, bariatric surgery, etc. within the past 5 years.

10. 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 6 months before screening.

11. Those who have participated in clinical trials of any dug or medial device within 6 months 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).

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

Related Conditions & MeSH terms

• Health

Intervention

Drug:
• Dabigatran Etexilate
Subjects will receive a single oral dose of 110mg (low dose specification in the instructions) or lower of dabigatran etexilate on an empty stomach on the morning of day 1 and day 16 of the trial period.

Dietary Supplement:
• D-mannose
Subjects will take 3g (1g*3 tablets) of D-mannose tablets every morning and evening from the 2nd day to the 15th day of the trial period, with a total of 6g/day (medium dose specification in the instructions).

Locations

Country	Name	City	State
China	Peking University Third Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University Third Hospital

Country where clinical trial is conducted

China, 

References & Publications (3)

Dong L, Xie J, Wang Y, Jiang H, Chen K, Li D, Wang J, Liu Y, He J, Zhou J, Zhang L, Lu X, Zou X, Wang XY, Wang Q, Chen Z, Zuo D. Mannose ameliorates experimental colitis by protecting intestinal barrier integrity. Nat Commun. 2022 Aug 16;13(1):4804. doi: 10.1038/s41467-022-32505-8. — View Citation

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

Marzolini C, Paus E, Buclin T, Kim RB. Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin Pharmacol Ther. 2004 Jan;75(1):13-33. doi: 10.1016/j.clpt.2003.09.012. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma concentration of dabigatran	Plasma concentration of dabigatran will be measured by liquid chromatography-tandem mass spectrometry	0 hours before and 2, 6, 10 and 24 hours after administration of dabigatran etexilate on the day 1 and day 16 of the trial period.
Primary	Serum concentrations of glycoomics such as D-mannose	Serum concentrations of glycoomics such as D-mannose will be measured by gas chromatography-tandem mass spectrometry	0 hours before administration of dabigatran etexilate of day 1 and 1.5 hours after D-mannose administration in the morning of day 2, day 8 and day 15.