Bioavailability of Dabigatran and Amiodarone After Multiple Oral Administrations of Dabigatran Etexilate With or Without Amiodarone as Single Dose in Healthy Male and Female Volunteers

NCT02171026 | Completed Phase 1

• 1 other identifier: 1160.57
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

Investigation of the bioavailability, safety and tolerability of dabigatran with and without concomitant administration of amiodarone and the bioavailability of amiodarone and desethylamiodarone after administration of a single dose of amiodarone with and without dabigatran

Conditions

Healthy

Outcome Measures

Primary Outcomes (8)

• AUCτ,ss (area under the concentration time curve of the analyte in plasma over one steady state dosing interval)

  pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 h post-dose on day 3, pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96 and 120 h post-dose on day 4

• Cmax,ss (maximum concentration of the analyte in plasma at steady state)

  pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 h post-dose on day 3, pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96 and 120 h post-dose on day 4

• AUC0-infinity (area under the concentration time curve of the analyte in plasma extrapolated to infinity)

  pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96 and 120 h post-dose

• Cmax (maximum concentration of the analyte in plasma)

  pre-dose on day 1 and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96 and 120 h post-dose

• Changes in aPTT (activated partial thromboplastin time)

  pre-dose on Day 1, 2, 3, and 4; on day 3 pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 h post-dose; on day 4 pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120 h post-dose

• Changes in ECT (ecarin clotting time)

  pre-dose on Day 1, 2, 3, and 4; on day 3 pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 h post-dose; on day 4 pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120 h post-dose

• AUERτ,ss (area under the effect ratio-time curve of the analyte in plasma at steady state over a uniform dosing interval τ)

  pre-dose on Day 1, 2, 3, and 4; on day 3 pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 h post-dose; on day 4 pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120 h post-dose

• ERmax,ss (maximum effect ratio in plasma at steady state)

  pre-dose on Day 1, 2, 3, and 4; on day 3 pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 h post-dose; on day 4 pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120 h post-dose

Secondary Outcomes (27)

• AUC0-tz,ss (area under the concentration-time curve of the analyte in plasma from the time point 0 after the last dose at steady state to the last quantifiable analyte plasma concentration within the uniform dosing interval τ)

  pre-dose on Day 1, 2, 3, and 4; on day 3 pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 h post-dose; on day 4 pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120 h post-dose

• tz,ss (time of last measurable concentration of the analyte in plasma within the dosing interval τ at steady state)

  pre-dose on Day 1, 2, 3, and 4; on day 3 pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 h post-dose; on day 4 pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120 h post-dose

• tmax,ss (time from last dosing to the maximum concentration of the analyte in plasma at steady state on Day 4)

  pre-dose Day 4 and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120 h post-dose

• CL/Fss (apparent clearance of the analyte in the plasma at steady state after extravascular multiple dose administration)

  pre-dose on Day 1, 2, 3, and 4; on day 3 pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 h post-dose; on day 4 pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120 h post-dose

• CLR,ss (renal clearance of the analyte at steady state determined over the dosing interval τ)

  pre-dose on Day 1, 2, 3, and 4; on day 3 pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24 h post-dose; on day 4 pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120 h post-dose

Study Arms (2)

Dabigatran etexilate + Amiodarone

EXPERIMENTAL

Drug: Dabigatran etexilate; Drug: Amiodarone

Amiodarone

ACTIVE COMPARATOR

Drug: Amiodarone

Interventions

Dabigatran etexilate DRUG

Dabigatran etexilate + Amiodarone

Amiodarone DRUG

Amiodarone; Dabigatran etexilate + Amiodarone

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males and females according to the following criteria:
• Based upon a complete medical history, including the physical examination, vital signs (BP, pulse rate (PR)), 12-lead ECG, clinical laboratory tests
• Aged \>=18 and \<=55 years
• Body mass index (BMI) \>=18.5 and BMI \<=29.9 kg/m2
• Signed and dated written informed consent prior to admission to the study according to GCP and local legislation

You may not qualify if:

• Clinically relevant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Relevant surgery of gastrointestinal tract
• History of any bleeding disorder or acute blood coagulation defect
• Diseases of the central nervous system, such as epilepsy; psychiatric disorders or neurological disorders
• History of relevant orthostatic hypotension, fainting spells or blackouts
• Chronic or relevant acute infections
• History of allergy/hypersensitivity, including drug allergy, which was deemed relevant to the study as judged by the investigator
• Intake of drugs with a long half-life (\>24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the study
• Use of drugs, which might have reasonably influenced the results of the study based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the study
• Participation in another study with an investigational drug within two months prior to administration or during the study
• Alcohol abuse (more than 60 g/day)
• Drug abuse
• Blood donation; more than 100 mL within four weeks prior to administration or during the study
• Excessive physical activities; within one week prior to administration or during the study
• Any laboratory value outside the reference range that was of clinical relevance

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Interventions

Dabigatran; Amiodarone

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzofurans

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2014
• First Posted: June 23, 2014
• Study Start: April 1, 2006
• Primary Completion: June 1, 2006
• Last Updated: June 23, 2014

Record last verified: 2014-06