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Photo for TADA Treatment with APO-Dabigatran Absorption

TADA Treatment with APO-Dabigatran Absorption

Official Title

Impact of Rabeprazole-induced Elevated Gastric pH on APO-Dabigatran exposure in healthy volunteers

Status

Ongoing

Overview

To determine any influence of PPIs on absorption of generic dabigatran available in Canada.

Optimization of the formulation of Pradaxa® (Dabigatran etexilate) provides consistent absorption in patients, independent of gastric pH. This has been demonstrated in clinical trials, where clinical outcomes with and without proton pump inhibitors (PPIs) were evaluated and shown to be equivalent. Many patients taking oral anticoagulants are elderly and have an increased gastric pH, often through commonly prescribed comedications such as PPIs. Generic formulations of dabigatran etexilate are required to demonstrate bioequivalence (BE) to the originator in young healthy volunteers to receive regulatory approval in Canada. One generic currently on the market in Canada is produced by Apotex Inc. (APO-Dabigatran). Apotex Inc. have changed the acid in the tablet from tartaric to fumaric. They were, however, not required to demonstrate the same BE in those with an altered gastric pH such as older patients or on comedications (e.g. PPIs).

Primary Endpoint

Dabigatran levels for APO-dabigatran (total and active metabolite) will be the assessment for the area under the concentration–time curve from baseline to the last quantifiable data point (AUC0–tz), and the maximum plasma concentration (Cmax) of total, with or without PPI. Secondary outcomes include dabigatran-specific assays such as diluted thrombin time (dTT) and aPTT. Safety will be assessed throughout the study by: frequency of AEs and vital signs (blood pressure, pulse rate).

Number of Patients

50

Number of Sites

1

Number of Countries

1

Study Period

2019-2020

Principal Investigator

John Eikelboom

Program Manager

Jessica Tyrwhitt