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

NCT06360055 | Recruiting

• 1 other identifier: M2024130
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Health

Keywords

D-mannose; Dabigatran Etexilate; P-glycoprotein; pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• 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.

• 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.

Study Arms (1)

D-mannose and dabigatran etexilate

EXPERIMENTAL

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. And they 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).

Drug: Dabigatran Etexilate; Dietary Supplement: D-mannose

Interventions

Dabigatran Etexilate DRUG

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.

Also known as: Pradaxa

D-mannose and dabigatran etexilate

D-mannose DIETARY_SUPPLEMENT

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).

D-mannose and dabigatran etexilate

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• With full capacity for civil conduct, the age of healthy male subjects is ≥18 years old and ≤45 years old
• Male weight ≥50 kg; body mass index (BMI) within the range of 19.0\~27.0 (including upper and lower limits)
• Creatinine clearance rate (CRCL: calculated by Cock croft-Gault equation, adult healthy subjects should have CRCL≥90mL/min

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.
• Diabetes mellitus; Impaired fasting glucose (IFG); Impaired glucose tolerance (IGT); Oral hypoglycemic agents (including the use of hypoglycemic agents for weight loss purposes).
• 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.
• 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 GPⅡb/Ⅲa receptor antagonists, ticlopidine, prasugrel, dextran, sulfinpyrazone, aspirin, etc.
• 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.
• 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).
• History of gastrointestinal surgery such as gallbladder or appendectomy, bariatric surgery, etc. within the past 5 years.
• 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.
• 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).
• Subjects who are considered by the investigator to have any factors that are not suitable for participating in this trial.

Sponsors & Collaborators

• Peking University Third Hospital: lead

Study Sites (1)

Peking University Third Hospital

Beijing, Beijing Municipality, 100191, China

RECRUITING

Related Publications (3)

• 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.

  PMID: 14749689 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 35974017 BACKGROUND

MeSH Terms

Interventions

Dabigatran; Mannose

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hexoses; Monosaccharides; Sugars; Carbohydrates

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: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: March 15, 2024
• First Posted: April 11, 2024
• Study Start: April 1, 2024
• Primary Completion: November 30, 2024
• Study Completion: December 31, 2024
• Last Updated: April 11, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)