Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Dabigatran Etexilate in Patients With Moderate Hepatic Impairment Compared to Subjects With Normal Hepatic Function

NCT02170571 | Completed Phase 1

• 1 other identifier: 1160.51
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

Assessment of the effect of moderate liver impairment (Child-Pugh classification B) on the pharmacokinetics and pharmacodynamics of dabigatran after oral administration of dabigatran etexilate. Determination of safety and tolerability of dabigatran upon administration to hepatically impaired patients and healthy subjects (matched pairs)

Conditions

Hepatic Insufficiency

Outcome Measures

Primary Outcomes (4)

• AUC0-infinity (area under the concentration time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)

  pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours

• Cmax (maximum concentration of the analyte in plasma)

  pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours

• CL/F (apparent clearance of the analyte in the plasma after extravascular administration)

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

• concentration-response relationship of dabigatran assessed by analysis of activated partial thromboplastin time (aPTT), ecarin clotting time (ECT) , prothrombin time (PT) expressed as international normalised ratio (INR), and thrombin time (TT)

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

Secondary Outcomes (16)

• AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)

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

• AUCt1-t2 (Area under the concentration time curve of the analyte in plasma over the time interval t1 to t2)

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

• tmax (time from dosing to the maximum concentration of the analyte in plasma)

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

• λz ( terminal rate constant in plasma)

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

• t1/2 ( terminal half-life of the analyte in plasma)

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

Study Arms (1)

Dabigatran etexilate

EXPERIMENTAL

Drug: Dabigatran etexilate

Interventions

Dabigatran etexilate DRUG

Dabigatran etexilate

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy age-, weight-, and sex-matched subjects determined by results of screening with normal hepatic function (group 1)
• Hepatically impaired subjects determined by results of screening classified as Child-Pugh B (group 2)
• Signed written informed consent in accordance with Good Clinical Practice (GCP) and local legislation
• Age \>=18 and \<=75 years
• BMI \>=18.0 and \<=32 kg/m2, at least 45 kg for females
• Creatinine clearance \>80 mL/min according to Cockcroft \& Gault

You may not qualify if:

• Healthy subjects (Group 1) who met any of the following criteria should not be entered into this trial:
• Any finding of the medical examination (including blood pressure, pulse rate, and electrocardiogram) deviating from normal and of clinical relevance
• Clinically relevant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic or hormonal disorders
• Surgery of gastrointestinal tract (except appendectomy, cholecystectomy, herniotomy)
• Clinically relevant diseases of the central nervous system
• Relevant history of orthostatic hypotension, fainting spells or blackouts
• Evidence of blood dyscrasia, haemorrhagic diathesis, severe thrombocytopenia, cerebrovascular haemorrhage, bleeding tendencies associated with active ulceration or overt bleeding of gastrointestinal, respiratory or genitourinary tract or any disease or condition with haemorrhagic tendencies (e.g. cerebral aneurysm, dissecting aorta, central nervous system (CNS) trauma, retinopathy, nephrolithiasis)
• Recent or contemplated diagnostic or therapeutic procedures with potential for uncontrollable bleeding (e.g. spinal puncture, lumbar block anaesthesia, surgery of CNS or eye or surgery resulting in large open surfaces) within 14 days before or after drug administration of this clinical trial
• Chronic or relevant acute infections
• History of allergy/hypersensitivity (including drug allergy), which is deemed relevant to the trial as judged by the investigator
• For women with childbearing potential: no reliable contraception (accepted methods are intra-uterine device, hormonal contraceptives, bilateral tubal ligation, hysterectomy, condoms) or pregnancy (known or detected by a positive pregnancy test) or breast feeding period
• Intake of drugs with a long half-life (\> 24 hours) (\< 1 month prior to administration or during the trial)
• Use of any drugs, within 14 days prior to administration or during the trial
• Participation in another trial with an investigational drug (\< 2 months prior to administration or during trial)
• Drug abuse

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Conditions

Hepatic Insufficiency

Interventions

Dabigatran

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

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

Study Design

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

Study Record Dates

• First Submitted: June 20, 2014
• First Posted: June 23, 2014
• Study Start: July 1, 2005
• Primary Completion: December 1, 2005
• Last Updated: June 23, 2014

Record last verified: 2014-06