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

Boehringer Ingelheim24 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Healthy

Interventions

Dabigatran etexilateDRUG

AmiodaroneDRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: Healthy males and females according to the following criteria: 1. Based upon a complete medical history, including the physical examination, vital signs (BP, pulse rate (PR)), 12-lead ECG, clinical laboratory tests 2. Aged \>=18 and \<=55 years 3. Body mass index (BMI) \>=18.5 and BMI \<=29.9 kg/m2 4. Signed and dated written informed consent prior to admission to the study according to GCP and local legislation Exclusion Criteria: 1. Clinically relevant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 2. Relevant surgery of gastrointestinal tract 3. History of any bleeding disorder or acute blood coagulation defect 4. Diseases of the central nervous system, such as epilepsy; psychiatric disorders or neurological disorders 5. History of relevant orthostatic hypotension, fainting spells or blackouts 6. Chronic or relevant acute infections 7. History of allergy/hypersensitivity, including drug allergy, which was deemed relevant to the study as judged by the investigator 8. 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 9. 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 10. Participation in another study with an investigational drug within two months prior to administration or during the study 11. Alcohol abuse (more than 60 g/day) 12. Drug abuse 13. Blood donation; more than 100 mL within four weeks prior to administration or during the study 14. Excessive physical activities; within one week prior to administration or during the study 15. Any laboratory value outside the reference range that was of clinical relevance 16. Inability to comply with dietary regimen of study centre 17. Females of child bearing potential who were pregnant, breast feeding or who were either not surgically sterile or were sexually active and not using an acceptable, i.e. highly effective with a Pearl index \>1%, form of contraception as either the oral contraceptives since at least two months and the double barrier method, i.e. intrauterine device with spermicide and condom for the male partner 18.) Male subjects had to agree to minimize the risk of female partners becoming pregnant from the first dosing day until 3 months after the completion of the post-study medical. Acceptable methods of contraception comprised barrier contraception and a medically accepted contraceptive method for the female partner (intrauterine device with spermicide, hormonal contraceptive since at least two month). 19.) Abnormal thyroid stimulating hormone (TSH) at screening

Outcomes

Primary Outcomes

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

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

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

Data from ClinicalTrials.gov

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Secondary Outcomes

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)

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

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

Time frame: 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)

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

Cmin,ss (minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ)

tmin,ss (time from last dosing to the minimum concentration of the analyte in plasma at steady state over a uniform dosing interval τ)

Cpre,ss (pre-dose concentration of the analyte in plasma at steady state immediately before administration of the next dose)

MRTp.o.,ss (mean residence time of the analyte in the body at steady state after oral administration)

Vz/Fss (apparent volume of distribution of the analyte during the terminal phase λz at steady state following an extravascular administration)

Aeτ,ss (amount of the analyte eliminated in urine at steady state over an uniform dosing interval τ)

Time frame: pre-dose, 0-12 h and 12-24 h post-dose on days 3 and 4

feτ,ss (fraction of the analyte eliminated in urine at steady state over a uniform dosing interval τ)

Time frame: pre-dose, 0-12 h and 12-24 h post-dose on days 3 and 4

AUC 0-tz (area under the concentration-time curve of the analyte in plasma over the time interval 0 to the last quantifiable analyte plasma concentration after single dose administration)