Diabetes Mellitus, Type 2
Conditions
Brief summary
The objective of this trial is to investigate the pharmacokinetics and pharmacodynamics of linagliptin (BI 1356) 5 mg administered orally in patients with Type 2 diabetes mellitus of African American origin.
Interventions
DRUGlinagliptin QD (once daily) for 7 days
dipeptidyl peptidase IV (DPP-4) activity will be measured as PD response to drug administration
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Glycosylated haemoglobin \>=7 and \<= 10% 2. Age \>=21 and \<= 65 3. Body Mass Index \>=18.5 and \<=38 kg/m2 4. African American origin 5. Signed and dated informed consent prior to admission to the study
Exclusion criteria
1. Any finding of the medical examination considered clinically relevant by the Investigator 2. Clinically relevant concomitant diseases like renal insufficiency, cardiac insufficiency New York Heart Association (NYHA) II-IV, known cardiovascular disease including hypertension \>160-100 mmHg (under current treatment), stroke and transient ischemic attack (TIA). 3. Clinically relevant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders besides type 2 diabetes 4. Clinically relevant diseases of central nervous system or psychiatric disorders or relevant neurological disorders besides polyneuropathy 5. Diagnosis of sickle cell anemia or known chronic anemia 6. History of chronic or relevant infections (for example human immunodeficieny virus (HIV), Hepatitis B) 7. History of relevant allergy/hypersensitivity 8. Intake of drugs with a long half life (\>24hours) within at least one month or less than 10 half lives of the respective drug prior to administration except allowed co medication 9. Alcohol abuse, drug abuse 10. Any laboratory value of clinical relevance that is outside an acceptable range 11. Change of drug dosing of allowed co medication 12. Any (electrocardiogram) ECG value outside the reference range and of clinical relevance. 13. Fasted glucose \>270 mg/dl or randomly determined blood glucose \>400 mg/dl on two consecutive days during screening or wash out 14. Serum creatinine above upper limit normal at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Linagliptin: AUC_τ,ss | 24 hours | area under the concentration time curve (AUC\_τ) of linagliptin in plasma at steady state over a uniform dosing interval |
| Linagliptin: C_max,ss | 24 hours | maximum concentration of linagliptin in plasma at steady state |
| DPP-4 Inhibition: E_24,ss | One single measurement 24 h after drug administration under steady state conditions | Plasma DPP-4 inhibition at trough under steady state conditions. Plasma DPP-4 inhibition is derived by calculating (1-(activity in presence of linagliptin)/baseline activity))\*100%, where 'activity' is the activity of the DPP-IV enzyme. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Linagliptin: AUC_0-24 | 24 hours | area under the concentration time curve of linagliptin in plasma over the time interval from 0 to 24h after administration of the first dose |
| Treatment Emergent Adverse Events | 21 days | Frequency of patients with AEs |
| DPP-4 Inhibition: E_24 | One single measurement 24 h after drug administration | Plasma DPP-4 inhibition 24 hours after first dose. Plasma DPP-4 inhibition is derived by calculating (1-(activity in presence of linagliptin)/baseline activity))\*100%, where 'activity' is the activity of the DPP-IV enzyme. |
| Linagliptin: C_max | 24h | maximum concentration of linagliptin in plasma on Day 1 |
| Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities | 21 days | 12-lead-Electrocardiogram (ECG), vital sign (blood pressure and pulse rate), physical finding and laboratory abnormalities |
| Patients With Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities Reported as an Adverse Event | 21 days | Patients with Electrocardiogram (ECG), vital signs, physical finding reported as an adverse event |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Linagliptin 5mg Linagliptin 5mg once daily | 41 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Other reason (not specified) | 1 |
Baseline characteristics
| Characteristic | Linagliptin 5mg |
|---|---|
| Age, Continuous | 50.5 Years STANDARD_DEVIATION 9.8 |
| Body mass index (BMI) continuous | 30.93 kg/m^2 STANDARD_DEVIATION 3.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Black / African American | 41 Participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 41 |
| serious Total, serious adverse events | 0 / 41 |
Outcome results
Primary
DPP-4 Inhibition: E_24,ss
Plasma DPP-4 inhibition at trough under steady state conditions. Plasma DPP-4 inhibition is derived by calculating (1-(activity in presence of linagliptin)/baseline activity))\*100%, where 'activity' is the activity of the DPP-IV enzyme.
Time frame: One single measurement 24 h after drug administration under steady state conditions
Population: Treated set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Linagliptin 5mg | DPP-4 Inhibition: E_24,ss | 84.7 Percent (of inhibition) |
Primary
Linagliptin: AUC_τ,ss
area under the concentration time curve (AUC\_τ) of linagliptin in plasma at steady state over a uniform dosing interval
Time frame: 24 hours
Population: Treated set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin 5mg | Linagliptin: AUC_τ,ss | 194 nmol*h/L | Geometric Coefficient of Variation 25.8 |
Primary
Linagliptin: C_max,ss
maximum concentration of linagliptin in plasma at steady state
Time frame: 24 hours
Population: Treated set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin 5mg | Linagliptin: C_max,ss | 16.4 nmol/L | Geometric Coefficient of Variation 40.9 |
Secondary
DPP-4 Inhibition: E_24
Plasma DPP-4 inhibition 24 hours after first dose. Plasma DPP-4 inhibition is derived by calculating (1-(activity in presence of linagliptin)/baseline activity))\*100%, where 'activity' is the activity of the DPP-IV enzyme.
Time frame: One single measurement 24 h after drug administration
Population: Treated set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Linagliptin 5mg | DPP-4 Inhibition: E_24 | 75.2 Percent (of inhibition) |
Secondary
Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities
12-lead-Electrocardiogram (ECG), vital sign (blood pressure and pulse rate), physical finding and laboratory abnormalities
Time frame: 21 days
Population: All treated patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Linagliptin 5mg | Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities | ECG abnormalities | 0 Participants |
| Linagliptin 5mg | Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities | Vital signs abnormalities | 0 Participants |
| Linagliptin 5mg | Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities | Physical finding abnormalities | 0 Participants |
| Linagliptin 5mg | Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities | Laboratory finding abnormalities | 5 Participants |
Secondary
Linagliptin: AUC_0-24
area under the concentration time curve of linagliptin in plasma over the time interval from 0 to 24h after administration of the first dose
Time frame: 24 hours
Population: Treated set- All patients with values for the area under the concentration time curve of the analyte in plasma over the time interval from 0 to 24 h after administration of the first dose (AUC\_0-24) for Linagliptin
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin 5mg | Linagliptin: AUC_0-24 | 137 nmol*h/L | Geometric Coefficient of Variation 32.4 |
Secondary
Linagliptin: C_max
maximum concentration of linagliptin in plasma on Day 1
Time frame: 24h
Population: Treated set - All patients with values for the maximum measured concentration of linagliptin in plasma (C\_max)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Linagliptin 5mg | Linagliptin: C_max | 10.9 nmol/L | Geometric Coefficient of Variation 57.6 |
Secondary
Patients With Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities Reported as an Adverse Event
Patients with Electrocardiogram (ECG), vital signs, physical finding reported as an adverse event
Time frame: 21 days
Population: All treated patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Linagliptin 5mg | Patients With Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities Reported as an Adverse Event | 0 Participants |
Secondary
Treatment Emergent Adverse Events
Frequency of patients with AEs
Time frame: 21 days
Population: All treated patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Linagliptin 5mg | Treatment Emergent Adverse Events | Patients with any adverse events (AEs) | 16 Participants |
| Linagliptin 5mg | Treatment Emergent Adverse Events | Patients with severe AEs | 0 Participants |
| Linagliptin 5mg | Treatment Emergent Adverse Events | Patients with drug-related AEs | 7 Participants |
| Linagliptin 5mg | Treatment Emergent Adverse Events | Discontinuation due to AEs | 0 Participants |