Effect of Inhibitors of the Proton Pump on Intestinal Transporters (BIPP)

Effect of Inhibitors of the Proton Pump on Intestinal Transporters and Their Impact on the Pharmacokinetics of Dabigatran - Mechanistic and Clinical Approach -BIPP Study

Dabigatran etexilate is a novel oral anticoagulant. It is indicated in venous thromboembolic prevention in orthopedic surgery and has recently shown greater efficiency and tolerance as anticoagulants in preventing thromboembolism in atrial fibrillation. However, it increases the risk of gastrointestinal bleeding compared to standard treatment (AVK) [3]. In these circumstances the risk / benefit of dabigatran could be improved by combining it with gastric protectors such as inhibitor drugs proton pump (IPP).

Investigators want to evaluate the pharmacokinetic and pharmacodynamic effects of co-administration of these two IPP (omeprazole, rabeprazole) with dabigatran in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Dabigatran; Drug: Rabeprazole and Dabigatran; Drug: Omeprazole and Dabigatran

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Saint-etienne, France, 42000
    • Chu de Saint-Etienne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• weight between 60 and 85 kg
• normal clinical exam
• normal biological exam

Exclusion Criteria:

• hypersensitivity to dabigatran or any of its excipients
• hypersensitivity to omeprazole or rabeprazole or any of its excipients
• previous history of hemorrhagic disease
• insufficiency liver
• severe kidney failure
• peptic ulcer
• Any drug taken during the week before the start of the study
• smoker
• Consumption of grapefruit juice
• practice of violent sport

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Period " Dabigatran"; Washout period (at least 6 days); Period " Rabeprazole + Dabigatran"; Washout period (at least 6 days); Period " Omeprazole + Dabigatran"	Drug: Dabigatran; dabigatran etexilate 150 mg/day (1 day); Drug: Rabeprazole and Dabigatran; rabeprazole 20 mg / day for 5 days, then the 6th day concomitant rabeprazole 20 mg of dabigatran etexilate 150 mg; Drug: Omeprazole and Dabigatran; omeprazole 20 mg / day for 5 days, then the sixth day concomitant omeprazole 20 mg and 150 mg dabigatran etexilate
Experimental: Arm B; Period "Rabeprazole + Dabigatran "; Washout period (at least 6 days); Period " Dabigatran"; Washout period (at least 6 days); Period " Omeprazole + Dabigatran"	Drug: Dabigatran; dabigatran etexilate 150 mg/day (1 day); Drug: Rabeprazole and Dabigatran; rabeprazole 20 mg / day for 5 days, then the 6th day concomitant rabeprazole 20 mg of dabigatran etexilate 150 mg; Drug: Omeprazole and Dabigatran; omeprazole 20 mg / day for 5 days, then the sixth day concomitant omeprazole 20 mg and 150 mg dabigatran etexilate
Experimental: Arm C; Period " Rabeprazole + Dabigatran"; Period " Omeprazole + Dabigatran"; Period " Dabigatran"	Drug: Dabigatran; dabigatran etexilate 150 mg/day (1 day); Drug: Rabeprazole and Dabigatran; rabeprazole 20 mg / day for 5 days, then the 6th day concomitant rabeprazole 20 mg of dabigatran etexilate 150 mg; Drug: Omeprazole and Dabigatran; omeprazole 20 mg / day for 5 days, then the sixth day concomitant omeprazole 20 mg and 150 mg dabigatran etexilate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC) from plasma concentrations of dabigatran	Area under the curve (AUC) from plasma concentrations of dabigatran	baseline after each dose of dabigatran etexilate.
Area under the curve (AUC) from plasma concentrations of dabigatran		0.25 hours after each dose of dabigatran etexilate.
Area under the curve (AUC) from plasma concentrations of dabigatran		0.5 hours after each dose of dabigatran etexilate.
Area under the curve (AUC) from plasma concentrations of dabigatran		1 hour after each dose of dabigatran etexilate.
Area under the curve (AUC) from plasma concentrations of dabigatran		1.5 hours after each dose of dabigatran etexilate.
Area under the curve (AUC) from plasma concentrations of dabigatran		2 hours after each dose of dabigatran etexilate.
Area under the curve (AUC) from plasma concentrations of dabigatran		3 hours after each dose of dabigatran etexilate.
Area under the curve (AUC) from plasma concentrations of dabigatran		6 hours after each dose of dabigatran etexilate.
Area under the curve (AUC) from plasma concentrations of dabigatran		8 hours after each dose of dabigatran etexilate.
Area under the curve (AUC) from plasma concentrations of dabigatran		12 hours after each dose of dabigatran etexilate.
Area under the curve (AUC) from plasma concentrations of dabigatran		24 hours after each dose of dabigatran etexilate.

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Investigators: Principal Investigator: Laurent BERTOLETTI, MD PhD, Chu de Saint-Etienne

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: August 13, 2015
• First Submitted That Met QC Criteria: August 13, 2015
• First Posted (Estimate): August 14, 2015

Study Record Updates

• Last Update Posted (Estimate): January 25, 2016
• Last Update Submitted That Met QC Criteria: January 22, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: volunteers
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Anti-Ulcer Agents; Proton Pump Inhibitors; Dabigatran; Rabeprazole; Omeprazole
• Other Study ID Numbers: 1208088; 140096A-21 (Other Identifier: ANSM); 2013-004932-31 (EudraCT Number)