NCT04157881

Brief Summary

Open-label, crossover study recruiting 46 healthy male volunteers comparing the absorption of APO-dabigatran 150 mg per oral (PO) in the absence or presence of a proton pump inhibitor. Participants will serve as their own control when comparing dabigatran exposure in the absence or presence of the proton pump inhibitor, Rabeprazole 20 mg.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
46

participants targeted

Target at below P25 for phase_4 atrial-fibrillation

Timeline
Completed

Started Jan 2020

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 1, 2019

Completed
7 days until next milestone

First Posted

Study publicly available on registry

November 8, 2019

Completed
2 months until next milestone

Study Start

First participant enrolled

January 3, 2020

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 18, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 18, 2022

Completed
Last Updated

March 21, 2022

Status Verified

March 1, 2021

Enrollment Period

2 years

First QC Date

November 1, 2019

Last Update Submit

March 18, 2022

Conditions

Atrial FibrillationVenous Thromboembolism

Outcome Measures

Primary Outcomes (2)

  • 24-hour APO-Dabigatran exposure by peak concentration

    As measured by peak concentration (Cmax)

    24 Hours

  • 24-hour APO-Dabigatran exposure

    As measured by area under the curve (AUC)

    24 Hours

Secondary Outcomes (4)

  • Area under the curve Dilute Thrombin time (dTT)

    24 hours

  • Maximum Dilute Thrombin time (dTT)

    24 hours

  • Area under the curve activated partial thromboplastin time (aPTT)

    24 hours

  • Maximum activated partial thromboplastin time (aPTT)

    24 hours

Study Arms (2)

APO-Dabigatran

OTHER

Single dose 150mg APO-Dabigatran given with 24 hours of Pharmacokinetic (PK) testing post dose

Drug: APO-Dabigatran 150mg

APO-Dabigatran and Rabeprazole

OTHER

4-7 doses of rabeprazole followed by single dose 150mg APO-Dabigatran given with 24 hours of Pharmacokinetic (PK) testing post dose

Drug: RABEprazole 20 Mg Oral Delayed Release TabletDrug: APO-Dabigatran 150mg

Interventions

RABEprazole 20 Mg Oral Delayed Release TabletDRUG

Absorption of APO-Dabigatran measured with and without influence of rabeprazole

APO-Dabigatran and Rabeprazole
APO-Dabigatran 150mgDRUG

Absorption of APO-Dabigatran post single dose

APO-DabigatranAPO-Dabigatran and Rabeprazole

Eligibility Criteria

Age20 Years - 40 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • to 40 years old
  • Body mass index 18-30 kg/m2
  • Male. Those able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information sheet.

You may not qualify if:

  • Any documented history of heart, lung, liver, kidney, gastrointestinal, genitourinary, musculoskeletal or endocrine disorders or other systemic illness not specifically listed.
  • Regular use of any medications or herbal supplements/remedies (e.g. St. John's wort).
  • Laboratory values outside of reference range that may compromise safety or validity of the trial.
  • Smoking or alcohol consumption such that the investigators feel that they will not be able to comply with the trial protocol.
  • Measures at screening outside of the reference ranges for systolic and diastolic blood pressure (\>140/90) and pulse rate (\>90/min).
  • Patients who are not expected to comply with the protocol requirements or not expected to complete the trial as scheduled (includes any condition that, in the investigator's opinion, makes the patient an unreliable trial participant).
  • Previous enrollment in this trial.
  • Currently enrolled in another investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s), or receiving other investigational treatment(s)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The Population Health Research Institute

Hamilton, Ontario, L8L 2X2, Canada

Location

Related Publications (6)

  • Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285-95. doi: 10.2165/00003088-200847050-00001.

    PMID: 18399711BACKGROUND

  • Coppens M, Eikelboom JW, Gustafsson D, Weitz JI, Hirsh J. Translational success stories: development of direct thrombin inhibitors. Circ Res. 2012 Sep 14;111(7):920-9. doi: 10.1161/CIRCRESAHA.112.264903.

    PMID: 22982873BACKGROUND

  • Hurwitz A, Brady DA, Schaal SE, Samloff IM, Dedon J, Ruhl CE. Gastric acidity in older adults. JAMA. 1997 Aug 27;278(8):659-62.

    PMID: 9272898BACKGROUND

  • Sarah S. The pharmacology and therapeutic use of dabigatran etexilate. J Clin Pharmacol. 2013 Jan;53(1):1-13. doi: 10.1177/0091270011432169. Epub 2013 Jan 24.

    PMID: 23400738BACKGROUND

  • Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep 17;361(12):1139-51. doi: 10.1056/NEJMoa0905561. Epub 2009 Aug 30.

    PMID: 19717844BACKGROUND

  • Weitz JI, Earl KM, Leblanc K, Semchuk W, Jamali F. Establishing Therapeutic Equivalence of Complex Pharmaceuticals: The Case of Dabigatran. Can J Cardiol. 2018 Sep;34(9):1116-1119. doi: 10.1016/j.cjca.2018.05.023. Epub 2018 Jun 5.

    PMID: 30093297BACKGROUND

Related Links

MeSH Terms

Conditions

Atrial FibrillationVenous Thromboembolism

Interventions

RabeprazoleTablets, Enteric-Coated

Condition Hierarchy (Ancestors)

Arrhythmias, CardiacHeart DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and SymptomsThromboembolismEmbolism and ThrombosisVascular Diseases

Intervention Hierarchy (Ancestors)

2-PyridinylmethylsulfinylbenzimidazolesSulfoxidesSulfur CompoundsOrganic ChemicalsPyridinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsBenzimidazolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingDelayed-Action PreparationsDosage FormsPharmaceutical PreparationsTablets

Study Officials

  • John Eikelboom, MBBS, MSc

    Population Health Research Institute

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 1, 2019

First Posted

November 8, 2019

Study Start

January 3, 2020

Primary Completion

January 18, 2022

Study Completion

January 18, 2022

Last Updated

March 21, 2022

Record last verified: 2021-03

Locations

CA(1)