Hepatic InsufficiencyPhase 1NCT02183376
Pharmacokinetics and Pharmacodynamics of BI 1356 in Subjects With Different Degrees of Liver Impairment as Compared to Healthy Subjects
A Phase 1 study testing BI 1356 in people with Hepatic Insufficiency, run by Boehringer Ingelheim.
Trial summary
To investigate the influence of mild, moderate, and severe liver impairment on the pharmacokinetics and pharmacodynamics of linagliptin in comparison with a control group with normal hepatic function after single or multiple oral administration of 5 mg linagliptin tablets Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Insufficiency
- What is being tested?
- BI 1356
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- No sites listed yet
- Study dates
- Jul 2008to Mar 2009
- 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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients with hepatic impairment determined by results of screening classified as mild (Child-Pugh class A, score 6 points), moderate (Child-Pugh class B, score 7 to 9 points) or severe (Child-Pugh class C, score 10 to 15 points)
- Healthy males and females based on a complete medical history, including physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests
- Subjects in the respective groups were matched with regard to age (±10 years), weight (±20%) and gender
- Age 18 to 70 years, inclusive
- Body mass index 18.5 to 29.9 kg/m2, inclusive
- Creatinine clearance ≥80 mL/min (except for patients with severe hepatic impairment, see exclusion criteria) according to Cockroft \& Gault
- Signed and dated written informed consent prior to admission to the study in accordance with good clinical practice and local legislation
Who cannot join
- Surgery of the gastrointestinal tract (except appendectomy and oesophageal varices)
- Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders (except hepatoportal encephalopathy)
- History of relevant orthostatic hypotension, fainting spells, or blackouts
- Chronic or relevant acute infections (except non-progressive chronic hepatitis not being in a progressive state)
- History of relevant allergy or hypersensitivity (including allergy to study drug or its excipients)
- Use of drugs which might reasonably influence the results of the trial or prolong the QT or QTc intervals (based on the knowledge at the time of preparing the Clinical Trial Protocol) within 10 days prior to study drug administration or during the trial
Show all 33Show fewer
- Participation in another trial with an investigational drug within 2 months prior to study drug administration or during the trial
- Smoking (more than 10 cigarettes, 3 cigars, or 3 pipes per day)
- Inability to refrain from smoking on trial days
- Alcohol abuse (more than 60 g/day)
- Drug abuse
- Blood donation (>100 mL within 4 weeks prior to study drug administration or during the trial)
- Excessive physical activities (within 1 week prior to study drug administration or during the trial)
- Inability to comply with dietary regimen of trial site
- A marked baseline prolongation of QT or QTc intervals (e.g. repeated demonstration of a QTc interval >450 ms)
- A history of additional risk factors for torsade de pointes such as heart failure, severe hypokalemia (<3.0 mmol/L), family history of long QT syndrome
- Additional/modified exclusion criteria for healthy volunteers
- Any finding of the medical examination (including BP, PR, and ECG) deviating from normal and of clinical relevance
- Any evidence of a clinically relevant concomitant disease
- Intake of drugs with a long half-life (>24 h) within 1 month or less than 10 half-lives of the respective drug prior to study drug administration or during the trial
- Any laboratory value outside the reference range of clinical relevance
- Additional/modified exclusion criteria for patients with hepatic impairment
- Decompensated gastrointestinal, respiratory, cardiovascular, metabolic, immunological, or hormonal disorders
- Patients with severe liver impairment (Child-Pugh C): Severe concurrent renal dysfunction (e.g. due to hepatorenal syndrome) and a creatinine clearance <40mL/min
- Intake of drugs with a long half-life (>24 h) within 1 month or less than 10 half-lives of the respective drug prior to study drug administration or during the trial and intake of metformin; drugs taken for treatment of the underlying disease are excluded
- Any laboratory value outside the reference range that is of clinical relevance, except for parameters related to liver impairment (e.g. albumin, bilirubin, enzymes) and liver function tests according to Child-Pugh classification
- Additional exclusion criteria for female subjects
- Pregnancy or intention to become pregnant within 2 months of study completion
- Positive pregnancy test
- Lack of adequate contraception (e.g. sterilisation, intrauterine device) or have not been using a barrier method of contraception for at least 3 months prior to the study
- Unwillingness or inability to use a reliable method of barrier contraception (e.g. diaphragm with spermicidal cream or jelly or condoms with spermicidal foam), during the study and up to 2 months after completion or termination of the trial
- Unwillingness of partner to use condoms
- Lactation period
About this study
Official title: Pharmacokinetics and Pharmacodynamics of BI 1356 5 mg Once Daily in Male and Female Subjects With Different Degrees of Liver Impairment (Child Pugh Classification A-C) as Compared to Male and Female Healthy Subjects (a Non-blinded, Parallel Group Study of Phase I)
To investigate the influence of mild, moderate, and severe liver impairment on the pharmacokinetics and pharmacodynamics of linagliptin in comparison with a control group with normal hepatic function after single or multiple oral administration of 5 mg linagliptin tablets
- Conditions
- Hepatic Insufficiency
- Being tested
- BI 1356
- Medical subject headings
- Hepatic Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BI 1356Drug
| Study group | Role | What they receive |
|---|---|---|
| BI 1356 - healthy subjects | Experimental | Not described Receives: Drug: BI 1356 |
| BI 1356 - mild liver impairment | Experimental | Not described Receives: Drug: BI 1356 |
| BI 1356 - moderate liver impairment | Experimental | Not described Receives: Drug: BI 1356 |
| BI 1356 - severe liver impairment | Experimental | Not described Receives: Drug: BI 1356 |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUCτ,ss (area under the concentration time curve of the analyte in plasma over the time interval from 0 to 24 h after the last dose at steady state) for healthy patients and patients with mild and moderate liver impairment
Measured: up to day 12
Cmax,ss (maximum concentration of the analyte in plasma at steady state) for healthy patients and patients with mild and moderate liver impairment
Measured: up to day 12
AUC0-24 (area under the concentration time curve of the analyte in plasma over the time interval from 0 to 24 h after the first dose) for patients with severe liver impairment
Measured: up to 24 hours after drug administration
Cmax (maximum concentration of the analyte in plasma) for patients with severe liver impairment
Measured: up to day 6
Secondary outcomes (22)
Plasma protein binding
Measured: up to day 12
Model-derived AUCτ,ss for patients with severe liver impairment
Measured: up to day 6
Model-derived Cmax,ss for patients with severe liver impairment
Measured: up to day 6
Plasma dipeptidyl peptidase-4 (DPP-4) activity
Measured: up to day 6
Plasma DPP-4 concentration
Measured: Day 1 (Baseline)
Number of patients with adverse events
Measured: up to 47 days
Number of patients with clinically significant changes in vital signs (Blood Pressure (BP), Pulse Rate (PR))
Measured: Baseline, up to day 19
Number of patients with clinically relevant findings in 12-lead electrocardiogram (ECG)
Measured: Baseline, up to day 19
Number of patients with clinically relevant findings in clinical laboratory tests
Measured: Baseline, up to day 19
Assessment of tolerability by investigator on a 4-point scale
Measured: day 19
tmax(ss) (time from last dose to maximum concentration of the analyte in plasma after single dose/at steady state) for healthy patients and patients with mild and moderate liver impairment
Measured: up to day 12
C24(ss) (concentration of the analyte in plasma at steady state after administration of the first or last dose at the end of the dosing interval) for healthy patients and patients with mild and moderate liver impairment
Measured: up to day 12
λz(ss) (terminal rate constant in plasma after single dose/at steady state) for healthy patients and patients with mild and moderate liver impairment
Measured: up to day 12
t1/2(ss) (terminal half-life of the analyte in plasma after single dose/at steady state) for healthy patients and patients with mild and moderate liver impairment
Measured: up to day 12
MRTpo(ss) (mean residence time of the analyte in the body after oral administration after single dose/at steady state) for healthy patients and patients with mild and moderate liver impairment
Measured: up to day 12
CL/F(ss) (apparent clearance of the analyte in the plasma after extravascular administration after single dose/at steady state) for healthy patients and patients with mild and moderate liver impairment
Measured: up to day 12
Vz/F(ss) (apparent volume of distribution during the terminal phase λz following extravascular administration after single dose/at steady state) for healthy patients and patients with mild and moderate liver impairment
Measured: up to day 12
AUC0-24 (area under the concentration time curve of the analyte in plasma over the time interval from 0 extrapolated to 24 h after the first dose for multiple dose groups) for healthy patients and patients with mild and moderate liver impairment
Measured: up to 24 hours after the first dose
Cmax (maximum concentration of the analyte in plasma after the first dose in multiple dose groups) for healthy patients and patients with mild and moderate liver impairment
Measured: up to day 12
%AUCtz-∞ (percentage of area under the concentration-time curve of the analyte in plasma over the time interval from the time of the last quantifiable data point extrapolated to infinity after single dose) in patients with severe liver impairment
Measured: up to day 6
AUC0-∞ (area under the concentration time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity after single dose in patients with severe liver impairment)
Measured: up to day 6
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 after single dose in patients with severe liver impairment)
Measured: up to day 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2014 (estimated)
- Study startJul 2008
- Primary completionMar 2009
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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 33 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
- NCT02183376
- Sponsor's protocol ID
- 1218.27
- Status last verified
- Jul 2014
- First submitted
- 4 Jul 2014
- Last updated
- 8 Jul 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics and Pharmacodynamics of BI 1356 5 mg Once Daily in Male and Female Subjects With Different Degrees of Liver Impairment (Child Pugh Classification A-C) as Compared to Male and Female Healthy Subjects (a Non-blinded, Parallel Group Study of Phase I)
- ClinicalTrials.gov ID
- NCT02183376
- Acronym / sponsor ID
- 1218.27
- Conditions
- Hepatic Insufficiency
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Jul 2008
- Primary completion
- Mar 2009 (actual)
- First posted
- 8 Jul 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.
To investigate the influence of mild, moderate, and severe liver impairment on the pharmacokinetics and pharmacodynamics of linagliptin in comparison with a control group with normal hepatic function after single or multiple oral administration of 5 mg linagliptin tablets
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| BI 1356 - healthy subjects | Experimental | Drug: BI 1356 |
| BI 1356 - mild liver impairment | Experimental | Drug: BI 1356 |
| BI 1356 - moderate liver impairment | Experimental | Drug: BI 1356 |
| BI 1356 - severe liver impairment | Experimental | Drug: BI 1356 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients with hepatic impairment determined by results of screening classified as mild (Child-Pugh class A, score 6 points), moderate (Child-Pugh class B, score 7 to 9 points) or severe (Child-Pugh class C, score 10 to 15 points)
- Healthy males and females based on a complete medical history, including physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests
- Subjects in the respective groups were matched with regard to age (±10 years), weight (±20%) and gender
- Age 18 to 70 years, inclusive
- Body mass index 18.5 to 29.9 kg/m2, inclusive
Key exclusion criteria (33 listed)
- Surgery of the gastrointestinal tract (except appendectomy and oesophageal varices)
- Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders (except hepatoportal encephalopathy)
- History of relevant orthostatic hypotension, fainting spells, or blackouts
- Chronic or relevant acute infections (except non-progressive chronic hepatitis not being in a progressive state)
- History of relevant allergy or hypersensitivity (including allergy to study drug or its excipients)
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 |
|---|---|---|
| BI 1356 | Drug | BI 1356 - healthy subjects, BI 1356 - mild liver impairment, BI 1356 - moderate liver impairment, BI 1356 - severe liver impairment |
Primary outcome
AUCτ,ss (area under the concentration time curve of the analyte in plasma over the time interval from 0 to 24 h after the last dose at steady state) for healthy patients and patients with mild and moderate liver impairment
Time frame: up to day 12
Cmax,ss (maximum concentration of the analyte in plasma at steady state) for healthy patients and patients with mild and moderate liver impairment
Time frame: up to day 12
AUC0-24 (area under the concentration time curve of the analyte in plasma over the time interval from 0 to 24 h after the first dose) for patients with severe liver impairment
Time frame: up to 24 hours after drug administration
Cmax (maximum concentration of the analyte in plasma) for patients with severe liver impairment
Time frame: up to day 6
22 secondary outcomes
Plasma protein binding
Time frame: up to day 12
Model-derived AUCτ,ss for patients with severe liver impairment
Time frame: up to day 6
Model-derived Cmax,ss for patients with severe liver impairment
Time frame: up to day 6
Plasma dipeptidyl peptidase-4 (DPP-4) activity
Time frame: up to day 6
Plasma DPP-4 concentration
Time frame: Day 1 (Baseline)
Number of patients with adverse events
Time frame: up to 47 days
Number of patients with clinically significant changes in vital signs (Blood Pressure (BP), Pulse Rate (PR))
Time frame: Baseline, up to day 19
Number of patients with clinically relevant findings in 12-lead electrocardiogram (ECG)
Time frame: Baseline, up to day 19
Number of patients with clinically relevant findings in clinical laboratory tests
Time frame: Baseline, up to day 19
Assessment of tolerability by investigator on a 4-point scale
Time frame: day 19
tmax(ss) (time from last dose to maximum concentration of the analyte in plasma after single dose/at steady state) for healthy patients and patients with mild and moderate liver impairment
Time frame: up to day 12
C24(ss) (concentration of the analyte in plasma at steady state after administration of the first or last dose at the end of the dosing interval) for healthy patients and patients with mild and moderate liver impairment
Time frame: up to day 12
λz(ss) (terminal rate constant in plasma after single dose/at steady state) for healthy patients and patients with mild and moderate liver impairment
Time frame: up to day 12
t1/2(ss) (terminal half-life of the analyte in plasma after single dose/at steady state) for healthy patients and patients with mild and moderate liver impairment
Time frame: up to day 12
MRTpo(ss) (mean residence time of the analyte in the body after oral administration after single dose/at steady state) for healthy patients and patients with mild and moderate liver impairment
Time frame: up to day 12
CL/F(ss) (apparent clearance of the analyte in the plasma after extravascular administration after single dose/at steady state) for healthy patients and patients with mild and moderate liver impairment
Time frame: up to day 12
Vz/F(ss) (apparent volume of distribution during the terminal phase λz following extravascular administration after single dose/at steady state) for healthy patients and patients with mild and moderate liver impairment
Time frame: up to day 12
AUC0-24 (area under the concentration time curve of the analyte in plasma over the time interval from 0 extrapolated to 24 h after the first dose for multiple dose groups) for healthy patients and patients with mild and moderate liver impairment
Time frame: up to 24 hours after the first dose
Cmax (maximum concentration of the analyte in plasma after the first dose in multiple dose groups) for healthy patients and patients with mild and moderate liver impairment
Time frame: up to day 12
%AUCtz-∞ (percentage of area under the concentration-time curve of the analyte in plasma over the time interval from the time of the last quantifiable data point extrapolated to infinity after single dose) in patients with severe liver impairment
Time frame: up to day 6
AUC0-∞ (area under the concentration time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity after single dose in patients with severe liver impairment)
Time frame: up to day 6
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 after single dose in patients with severe liver impairment)
Time frame: up to day 6
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 8 Jul 2014.
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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 BI 1356 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 7 inclusion and 33 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 8 Jul 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?
AUCτ,ss (area under the concentration time curve of the analyte in plasma over the time interval from 0 to 24 h after the last dose at steady state) for healthy patients and patients with mild and moderate liver impairment (time frame: up to day 12). 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 8 Jul 2014; AzTrials last refreshed its copy on 8 Nov 2026.