Hepatic InsufficiencyPhase 1NCT02170571
Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Dabigatran Etexilate in Patients With Moderate Hepatic Impairment Compared to Subjects With Normal Hepatic Function
A Phase 1 study testing Dabigatran etexilate in people with Hepatic Insufficiency, run by Boehringer Ingelheim.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Insufficiency
- What is being tested?
- Dabigatran etexilate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- No sites listed yet
- Study dates
- Jul 2005to Dec 2005
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
- Blood donation or loss > 400 ml, < 1 month prior to administration or during the trial
- Excessive physical activities < 5 days prior to administration of study drug or during the trial
- Clinically relevant laboratory abnormalities
- Veins unsuited for i.v. puncture and administration of prolonged infusions on either arm (e.g. veins which are difficult to locate, access or puncture, veins with a tendency to rupture during or after puncture, etc.)
- Hepatically impaired subjects (Group 2) who met any of the following criteria should not be entered into this trial:
- Moderate and severe concurrent renal function impairment (e.g., due to hepato-renal syndrome)
- Clinically relevant gastrointestinal, 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, CNS trauma, retinopathy, nephrolithiasis) considered by the investigator or one of the coinvestigators to be clinically relevant
- 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
- 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
- Use of any drugs which have an influence on the blood clotting 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)
- Blood donation or loss > 400 ml, < 1 month prior to administration or during the trial
- Excessive physical activities < 5 days prior to administration of study drug or during the trial
- Clinically relevant laboratory abnormalities (except for liver function tests according to Child-Pugh classification), constellation of blood clotting parameters according to the judgment of the investigator
- Veins unsuited for i.v. puncture and administration of prolonged infusions on either arm (e.g. veins which are difficult to locate, access or puncture, veins with a tendency to rupture during or after puncture, etc.)
About this study
Official title: Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of 150 mg Dabigatran Etexilate p.o. in Patients With Moderate Hepatic Impairment Compared to Subjects With Normal Hepatic Function in a Monocentric, Open, Parallel-group Design
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
- Being tested
- Dabigatran etexilate
- Medical subject headings
- Hepatic Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dabigatran etexilateDrug
| Study group | Role | What they receive |
|---|---|---|
| Dabigatran etexilate | Experimental | Not described Receives: Drug: Dabigatran etexilate |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC0-infinity (area under the concentration time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h
MRTpo (mean residence time of the analyte in the body after oral administration)
Measured: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
Measured: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h
Ae0-72 (amount of analyte that is eliminated in urine from the time interval 0 to 72 h)
Measured: pre-dose over 12 h from day -1 till day 1 and post-dose from day 1 till day 4 in fractions of 0 - 12, 12 - 24, 24 - 48 and 48 - 72 h
fe0-72 (fraction of administered drug excreted unchanged in urine from time point 0 to 72 h)
Measured: pre-dose over 12 h from day -1 till day 1 and post-dose from day 1 till day 4 in fractions of 0 - 12, 12 - 24, 24 - 48 and 48 - 72 h
CLR,0-72 (renal clearance of the analyte in plasma from the time point 0 h until the time point 72 h)
Measured: pre-dose over 12 h from day -1 till day 1 and post-dose from day 1 till day 4 in fractions of 0 - 12, 12 - 24, 24 - 48 and 48 - 72 h
Plasma protein binding of dabigatran
Measured: before drug administration
Change in pulse rate
Measured: up to day 4
Change in systolic and diastolic blood pressure
Measured: up to day 4
Change in ECG
Measured: up to day 4
Occurrence of adverse events
Measured: up to Day 4
Assessment of tolerability by investigator on a four-point scale
Measured: up to day 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2014 (estimated)
- Study startJul 2005
- Primary completionDec 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic InsufficiencyStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02170571
- Sponsor's protocol ID
- 1160.51
- Status last verified
- Jun 2014
- First submitted
- 20 Jun 2014
- Last updated
- 23 Jun 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of 150 mg Dabigatran Etexilate p.o. in Patients With Moderate Hepatic Impairment Compared to Subjects With Normal Hepatic Function in a Monocentric, Open, Parallel-group Design
- ClinicalTrials.gov ID
- NCT02170571
- Acronym / sponsor ID
- 1160.51
- Conditions
- Hepatic Insufficiency
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Jul 2005
- Primary completion
- Dec 2005 (actual)
- First posted
- 23 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Dabigatran etexilate | Experimental | Drug: Dabigatran etexilate |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (35 listed)
- Healthy subjects (Group 1) who met any of the following criteria should not be entered into this trial:
- Hepatically impaired subjects (Group 2) who met any of the following criteria should not be entered into this trial:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dabigatran etexilate | Drug | Dabigatran etexilate |
Primary outcome
AUC0-infinity (area under the concentration time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h
16 secondary outcomes
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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h
MRTpo (mean residence time of the analyte in the body after oral administration)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
Time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h
Ae0-72 (amount of analyte that is eliminated in urine from the time interval 0 to 72 h)
Time frame: pre-dose over 12 h from day -1 till day 1 and post-dose from day 1 till day 4 in fractions of 0 - 12, 12 - 24, 24 - 48 and 48 - 72 h
fe0-72 (fraction of administered drug excreted unchanged in urine from time point 0 to 72 h)
Time frame: pre-dose over 12 h from day -1 till day 1 and post-dose from day 1 till day 4 in fractions of 0 - 12, 12 - 24, 24 - 48 and 48 - 72 h
CLR,0-72 (renal clearance of the analyte in plasma from the time point 0 h until the time point 72 h)
Time frame: pre-dose over 12 h from day -1 till day 1 and post-dose from day 1 till day 4 in fractions of 0 - 12, 12 - 24, 24 - 48 and 48 - 72 h
Plasma protein binding of dabigatran
Time frame: before drug administration
Change in pulse rate
Time frame: up to day 4
Change in systolic and diastolic blood pressure
Time frame: up to day 4
Change in ECG
Time frame: up to day 4
Occurrence of adverse events
Time frame: up to Day 4
Assessment of tolerability by investigator on a four-point scale
Time frame: up to day 4
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2014.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dabigatran etexilate in people with Hepatic Insufficiency, run by Boehringer Ingelheim.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUC0-infinity (area under the concentration time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) (time frame: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2014.