Renal InsufficiencyPhase 1NCT02191228
Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Single and Multiple Doses of Linagliptin Tablets in Patients With Different Degrees of Renal Impairment in Comparison to Subjects With Normal Renal Function
A Phase 1 study testing Linagliptin - single dose and Linagliptin - Multiple dose in people with Renal Insufficiency, run by Boehringer Ingelheim.
Trial summary
The main objective of this study was to assess the effect of normal and impaired renal function on the safety, pharmacokinetics, and pharmacodynamics of linagliptin following oral administration of 5 mg daily for 7 days (Groups 1 to 3), 5 mg daily for 10 days (Groups 6 and 7), or as a single dose (Groups 4 and 5) Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Renal Insufficiency
- What is being tested?
- Linagliptin - single dose and Linagliptin - Multiple dose
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- No sites listed yet
- Study dates
- Apr 2008to Feb 2010
- 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 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female subjects with normal renal function, defined as a Creatinine Clearance (CrCl) of >80 mL/min on screening (Group 1) , or male or female patients with Type 2 diabetes mellitus (T2DM) and normal renal function, defined as a CrCl of >80 mL/min on screening (Group 7)
- Male or female patients with Renal impairment (RI), determined by the value of CrCl on Screening estimated according to the Cockcroft-Gault formula. Patients were classified into groups by their CrCl values:
- Mild RI: CrCl>50 to ≤80 mL/min (Group 2)
- Moderate RI: CrCl>30 to ≤50 mL/min (Group 3)
- Severe RI: CrCl≤30 mL/min (Group 4)
- End-stage renal disease (ESRD): CrCl≤30 mL/min, requiring hemodialysis (Group 5)
Show all 10Show fewer
- T2DM and severe RI: CrCl≤30 mL/min (Group 6)
- Age 18 to 80 years
- BMI 18 to 40 kg/m2, and minimum body mass of at least 45 kg for females
- Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation
Who cannot join
- Participants (with or without RI) who met any of the following criteria were not included in this trial:
- Relevant gastrointestinal tract surgery (except appendectomy, cholecystectomy, or herniotomy)
- Diseases of the central nervous system, such as epilepsy, seizures, relevant neurological disorders, or psychiatric disorders
- History of relevant orthostatic hypotension, fainting spells or blackouts; systolic blood pressure <100 or >160 mm Hg, diastolic blood pressure <60 or >100 mm Hg, pulse rate <50 or >100 1/min
- Chronic or relevant acute infections
- History of allergy/hypersensitivity (including drug allergies) that were deemed relevant to the trial as judged by the investigator
Show all 30Show fewer
- Intake of drugs with a long half-life (>24 h) within at least one month prior to study start, or planned intake of study medication within ≤10 half-lives of administration of another medication. Medications that patients with RI were currently taking for treatment of renal disease were not included under this criterium.
- Use of medications during the trial or within 10 days prior to administration of study medication that might reasonably influence the results of the trial, based on knowledge at the time of protocol preparation. Co-medications known to inhibit or induce P-glycoprotein or CYP3A were not allowed. Inhibitors of P-glycoprotein or CYP3A include protease inhibitors (such as ritonavir, lopinavir, nelfinavir); azole antimycotics, (itraconazole, ketoconazole, miconazole); macrolide antibiotics, (clarithromycin, erythromycin); amiodarone, cimetidine, diltiazem, fluvoxamine, mibefradil, nefazodone, verapamil, tacrolimus, quinidine, reserpine, and cyclosporine A. Inducers of P-gp or CYP3A include carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, St. John's Wort and troglitazone. In uncertain cases, a case-by-case decision was made after consultation with the sponsor.
- Participation in a previous trial with an investigational drug within 2 months of study start if the previous trial was a multiple dose study, or within 1 month of study start if the previous trial was a single dose study
- Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
- Inability to refrain from smoking when confined to the study site on trial days
- Alcohol abuse (more than 60 g/day in males or more than 40 g/day in females)
- Drug abuse, in the investigator's judgment, based on review of the participant's history and urine screening for abused substances
- Veins unsuited for intravenous puncture on either arm (e.g. veins which were difficult to locate, access or puncture, veins with a tendency to rupture during or after puncture)
- Blood donation (more than 100 mL within 4 weeks prior to administration of study medication or during the trial)
- Excessive physical activities (within 48 h prior to start of the trial or during the trial)
- Any laboratory value outside the reference range that was of clinical relevance (exceptions were in patients with RI who had abnormal renal function tests or deviations of clinical laboratory values that were related to renal impairment)
- Inability to comply with the dietary regimen of study centre
- Inability to understand and comply with protocol requirements, instructions and protocol-stated restrictions
- For female patients
- Pregnancy
- Positive pregnancy test (human chorionic gonadotropin (β HCG) in urine))
- No adequate contraception in women of childbearing potential (adequate contraception was considered to be sterilisation, use of an intrauterine device, or use of oral contraception along with a barrier method)
- Lactation period
- Subjects with normal renal function (Group 1) and subjects with T2DM and normal renal function (Group 7) who met the following criterium were not included in this trial:
- Significant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders as judged by the investigator
- Patients with RI who met any of the following criteria were not included in this trial:
- Moderate and severe concurrent liver function impairment (for example, due to hepatorenal syndrome)
- Patients with significant diseases other than renal impairment were excluded. A significant disease was defined as a disease which in the opinion of the investigator put the patient at risk during participation in the study, could influence the results of the study, could influence the patient's ability to participate in the study, or was an unstable condition. Patients with diabetes (for Groups 1 to 5) or hypertension could be included in the trial if the disease was not significant according to these criteria.
- Haemoglobin <8 g/dL, indicating severe anaemia of renal origin (use of erythropoietin was allowed to maintain haematocrit)
About this study
Official title: Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Single and Multiple 5 mg Doses of Linagliptin Tablets in Patients With Different Degrees of Renal Impairment in Comparison to Subjects With Normal Renal Function in a Monocentric, Open, Parallel-group, Phase I Trial
The main objective of this study was to assess the effect of normal and impaired renal function on the safety, pharmacokinetics, and pharmacodynamics of linagliptin following oral administration of 5 mg daily for 7 days (Groups 1 to 3), 5 mg daily for 10 days (Groups 6 and 7), or as a single dose (Groups 4 and 5)
- Conditions
- Renal Insufficiency
- Being tested
- Linagliptin - single dose, Linagliptin - Multiple dose
- Medical subject headings
- Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Linagliptin - single doseDrug
Linagliptin - Multiple doseDrug
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Linagliptin in subjects with normal renal function Receives: Drug: Linagliptin - Multiple dose |
| Group 2 | Experimental | Linagliptin in patients with mild renal insufficiency (RI) Receives: Drug: Linagliptin - Multiple dose |
| Group 3 | Experimental | Linagliptin in patients with moderate RI Receives: Drug: Linagliptin - Multiple dose |
| Group 4 | Experimental | Linagliptin in patients with severe RI Receives: Drug: Linagliptin - single dose |
| Group 5 | Experimental | Linagliptin in patients with end-stage renal disease (ESRD) Receives: Drug: Linagliptin - single dose |
| Group 6 | Experimental | Linagliptin in patients with severe RI and Type 2 diabetes mellitus (T2DM) Receives: Drug: Linagliptin - Multiple dose |
| Group 7 | Experimental | Linagliptin in patients with normal renal function and T2DM Receives: Drug: Linagliptin - Multiple dose |
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 24h after the last dose at steady state) - multiple dose groups
Measured: up to 480 hours
Cmax,ss (maximum concentration of the analyte in plasma at steady state) - multiple dose groups
Measured: up to 480 hours
AUC0-24 (area under the concentration time curve of the analyte in plasma over the time interval from 0 to 24h after the first dose) - single dose groups
Measured: up to 24 hours
Cmax (maximum concentration of the analyte in plasma) - single dose groups
Measured: up to 264 hours
Secondary outcomes (22)
tmax,(ss) (time from last dosing to maximum concentration of the analyte in plasma after the first dose or at steady state) - multiple dose groups
Measured: up to 480 hours
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) - multiple dose groups
Measured: up to 480 hours
λz,(ss) (terminal rate constant in plasma after single dose/at steady state) - multiple dose groups
Measured: up to 480 hours
t1/2,(ss) (terminal half-life of the analyte in plasma after single dose/at steady state) - multiple dose groups
Measured: up to 480 hours
MRTpo,(ss) (mean residence time of the analyte in the body after single dose/at steady state after oral administration) - multiple dose groups
Measured: up to 480 hours
CL/F,(ss) (apparent clearance of the analyte in the plasma after extravascular administration after single dose/at steady state) - multiple dose groups
Measured: up to 480 hours
Vz/F,(ss) (apparent volume of distribution during the terminal phase λz after single dose/at steady state following extravascular administration) - multiple dose groups
Measured: up to 480 hours
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 severely impaired or end stage renal disease (ESRD) patients)
Measured: up to 264 hours
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 severely impaired or ESRD patients)
Measured: up to 264 hours
%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 severely impaired or ESRD patients)
Measured: up to 264 hours
Assessment of Plasma protein binding
Measured: predose Day 1
Model-derived AUCτ,ss in severely impaired or ESRD patients
Measured: up to 264 hours
Model-derived Cmax,ss in severely impaired or ESRD patients
Measured: up to 264 hours
Change in Dipeptidyl peptidase IV (DPP-4) activity in plasma
Measured: up to 480 hours
Number of patients with abnormal findings in physical examination
Measured: up to day 32
Number of patients with clinically significant changes in vital signs
Measured: up to day 32
Number of patients with abnormal changes 12-lead ECG (electrocardiogram)
Measured: up to day 32
Number of patients with abnormal changes in laboratory parameters
Measured: up to day 32
Number of patients with adverse events
Measured: up to 53 days
Assessment of tolerability by investigator on a 4-point scale
Measured: up to 480 hours
AUC0-24 (area under the concentration time curve of the analyte in plasma over the time interval from 0 to 24h after the first dose) - multiple dose groups
Measured: up to 24 hours
Cmax (maximum concentration of the analyte in plasma) - multiple dose groups
Measured: up to 480 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2014 (estimated)
- Study startApr 2008
- Primary completionFeb 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal 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
- 51 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
- NCT02191228
- Sponsor's protocol ID
- 1218.26
- Status last verified
- Jun 2014
- First submitted
- 15 Jul 2014
- Last updated
- 16 Jul 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Single and Multiple 5 mg Doses of Linagliptin Tablets in Patients With Different Degrees of Renal Impairment in Comparison to Subjects With Normal Renal Function in a Monocentric, Open, Parallel-group, Phase I Trial
- ClinicalTrials.gov ID
- NCT02191228
- Acronym / sponsor ID
- 1218.26
- Conditions
- Renal Insufficiency
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Apr 2008
- Primary completion
- Feb 2010 (actual)
- First posted
- 16 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.
The main objective of this study was to assess the effect of normal and impaired renal function on the safety, pharmacokinetics, and pharmacodynamics of linagliptin following oral administration of 5 mg daily for 7 days (Groups 1 to 3), 5 mg daily for 10 days (Groups 6 and 7), or as a single dose (Groups 4 and 5)
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: Linagliptin - Multiple doseLinagliptin in subjects with normal renal function |
| Group 2 | Experimental | Drug: Linagliptin - Multiple doseLinagliptin in patients with mild renal insufficiency (RI) |
| Group 3 | Experimental | Drug: Linagliptin - Multiple doseLinagliptin in patients with moderate RI |
| Group 4 | Experimental | Drug: Linagliptin - single doseLinagliptin in patients with severe RI |
| Group 5 | Experimental | Drug: Linagliptin - single doseLinagliptin in patients with end-stage renal disease (ESRD) |
| Group 6 | Experimental | Drug: Linagliptin - Multiple doseLinagliptin in patients with severe RI and Type 2 diabetes mellitus (T2DM) |
| Group 7 | Experimental | Drug: Linagliptin - Multiple doseLinagliptin in patients with normal renal function and T2DM |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female subjects with normal renal function, defined as a Creatinine Clearance (CrCl) of >80 mL/min on screening (Group 1) , or male or female patients with Type 2 diabetes mellitus (T2DM) and normal renal function, defined as a CrCl of >80 mL/min on screening (Group 7)
- Male or female patients with Renal impairment (RI), determined by the value of CrCl on Screening estimated according to the Cockcroft-Gault formula. Patients were classified into groups by their CrCl values:
- Age 18 to 80 years
- BMI 18 to 40 kg/m2, and minimum body mass of at least 45 kg for females
- Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation
Key exclusion criteria (30 listed)
- Participants (with or without RI) who met any of the following criteria were not included in this trial:
- Relevant gastrointestinal tract surgery (except appendectomy, cholecystectomy, or herniotomy)
- Diseases of the central nervous system, such as epilepsy, seizures, relevant neurological disorders, or psychiatric disorders
- History of relevant orthostatic hypotension, fainting spells or blackouts; systolic blood pressure <100 or >160 mm Hg, diastolic blood pressure <60 or >100 mm Hg, pulse rate <50 or >100 1/min
- Chronic or relevant acute infections
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 |
|---|---|---|
| Linagliptin - single dose | Drug | Group 4, Group 5 |
| Linagliptin - Multiple dose | Drug | Group 1, Group 2, Group 3, Group 6, Group 7 |
Primary outcome
AUCτ,ss (area under the concentration time curve of the analyte in plasma over the time interval from 0 to 24h after the last dose at steady state) - multiple dose groups
Time frame: up to 480 hours
Cmax,ss (maximum concentration of the analyte in plasma at steady state) - multiple dose groups
Time frame: up to 480 hours
AUC0-24 (area under the concentration time curve of the analyte in plasma over the time interval from 0 to 24h after the first dose) - single dose groups
Time frame: up to 24 hours
Cmax (maximum concentration of the analyte in plasma) - single dose groups
Time frame: up to 264 hours
22 secondary outcomes
tmax,(ss) (time from last dosing to maximum concentration of the analyte in plasma after the first dose or at steady state) - multiple dose groups
Time frame: up to 480 hours
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) - multiple dose groups
Time frame: up to 480 hours
λz,(ss) (terminal rate constant in plasma after single dose/at steady state) - multiple dose groups
Time frame: up to 480 hours
t1/2,(ss) (terminal half-life of the analyte in plasma after single dose/at steady state) - multiple dose groups
Time frame: up to 480 hours
MRTpo,(ss) (mean residence time of the analyte in the body after single dose/at steady state after oral administration) - multiple dose groups
Time frame: up to 480 hours
CL/F,(ss) (apparent clearance of the analyte in the plasma after extravascular administration after single dose/at steady state) - multiple dose groups
Time frame: up to 480 hours
Vz/F,(ss) (apparent volume of distribution during the terminal phase λz after single dose/at steady state following extravascular administration) - multiple dose groups
Time frame: up to 480 hours
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 severely impaired or end stage renal disease (ESRD) patients)
Time frame: up to 264 hours
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 severely impaired or ESRD patients)
Time frame: up to 264 hours
%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 severely impaired or ESRD patients)
Time frame: up to 264 hours
Assessment of Plasma protein binding
Time frame: predose Day 1
Model-derived AUCτ,ss in severely impaired or ESRD patients
Time frame: up to 264 hours
Model-derived Cmax,ss in severely impaired or ESRD patients
Time frame: up to 264 hours
Change in Dipeptidyl peptidase IV (DPP-4) activity in plasma
Time frame: up to 480 hours
Number of patients with abnormal findings in physical examination
Time frame: up to day 32
Number of patients with clinically significant changes in vital signs
Time frame: up to day 32
Number of patients with abnormal changes 12-lead ECG (electrocardiogram)
Time frame: up to day 32
Number of patients with abnormal changes in laboratory parameters
Time frame: up to day 32
Number of patients with adverse events
Time frame: up to 53 days
Assessment of tolerability by investigator on a 4-point scale
Time frame: up to 480 hours
AUC0-24 (area under the concentration time curve of the analyte in plasma over the time interval from 0 to 24h after the first dose) - multiple dose groups
Time frame: up to 24 hours
Cmax (maximum concentration of the analyte in plasma) - multiple dose groups
Time frame: up to 480 hours
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 16 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 Linagliptin - single dose and Linagliptin - Multiple dose in people with Renal 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 10 inclusion and 30 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 16 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 24h after the last dose at steady state) - multiple dose groups (time frame: up to 480 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 16 Jul 2014.