ongoing

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).

The objective of the TADA study is to determine any influence of PPIs on absorption of generic dabigatran available in Canada.

APO-dabigatran will be used for an open, cross-over design in up to 50 volunteers who will receive a single dose of 150 mg. Blood samples will be taken at defined time points: 0/trough, 30, 60, and 90 min and 2, 3, 4, 6, 8, and 24 h after administration. Volunteers will then undergo a wash-out period (4 days) while taking a PPI once daily (rabeprazole). On day 5, a repeat single APO-dabigatran 150 mg tablet will be administered in addition to the PPI. Blood sampling will occur as performed previously.

Primary endpoints:

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).

Study Type

Interventional - Drug

Study Design

Open-label crossover study

NO. of Countries

1

NO. of Sites

1

NO. of Participants

50

Study Period

2019-2020

Sponsor

PHRI

Boehringer Ingelheim

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