Effect of Inhibitors of the Proton Pump on Intestinal Transporters

NCT02524210 | Completed Phase 1

• 3 other identifiers: 12080882013-004932-31140096A-21
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

volunteers

Outcome Measures

Primary Outcomes (11)

• 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.

Study Arms (3)

Arm A

EXPERIMENTAL

* Period " Dabigatran" * Washout period (at least 6 days) * Period " Rabeprazole + Dabigatran" * Washout period (at least 6 days) * Period " Omeprazole + Dabigatran"

Drug: Dabigatran; Drug: Rabeprazole and Dabigatran; Drug: Omeprazole and Dabigatran

Arm B

EXPERIMENTAL

* Period "Rabeprazole + Dabigatran " * Washout period (at least 6 days) * Period " Dabigatran" * Washout period (at least 6 days) * Period " Omeprazole + Dabigatran"

Drug: Dabigatran; Drug: Rabeprazole and Dabigatran; Drug: Omeprazole and Dabigatran

Arm C

EXPERIMENTAL

* Period " Rabeprazole + Dabigatran" * Period " Omeprazole + Dabigatran" * Period " Dabigatran"

Drug: Dabigatran; Drug: Rabeprazole and Dabigatran; Drug: Omeprazole and Dabigatran

Interventions

Dabigatran DRUG

dabigatran etexilate 150 mg/day (1 day)

Arm A; Arm B; Arm C

Rabeprazole and Dabigatran DRUG

rabeprazole 20 mg / day for 5 days, then the 6th day concomitant rabeprazole 20 mg of dabigatran etexilate 150 mg;

Arm A; Arm B; Arm C

Omeprazole and Dabigatran DRUG

omeprazole 20 mg / day for 5 days, then the sixth day concomitant omeprazole 20 mg and 150 mg dabigatran etexilate

Arm A; Arm B; Arm C

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead

Study Sites (1)

CHU de SAINT-ETIENNE

Saint-Etienne, 42000, France

Location

MeSH Terms

Interventions

Dabigatran; Rabeprazole; Omeprazole

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals

Study Officials

• Laurent BERTOLETTI, MD PhD

  CHU de SAINT-ETIENNE

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2015
• First Posted: August 14, 2015
• Study Start: May 1, 2014
• Primary Completion: May 1, 2015
• Study Completion: December 1, 2015
• Last Updated: January 25, 2016

Record last verified: 2016-01

Locations

FR (1)