Pharmacokinetics and Pharmacodynamics Trial With Linagliptin (BI 1356) 5mg in African American Type 2 Diabetic Patients

Study Overview
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Brief Summary
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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.

Official Title
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An Open Label, Phase I Trial to Investigate the Pharmacokinetics and Pharmacodynamics of Linagliptin (BI 1356) 5 mg After Single and Multiple Oral Administration in Patients With Type 2 Diabetes Mellitus of African American Origin for 7 Days

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: linagliptin QD (once daily) for 7 days


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Glycosylated haemoglobin >=7 and <= 10% Age >=21 and <= 65 Body Mass Index >=18.5 and <=38 kg/m2 African American origin Signed and dated informed consent prior to admission to the study Exclusion criteria: Any finding of the medical examination considered clinically relevant by the Investigator 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). Clinically relevant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders besides type 2 diabetes Clinically relevant diseases of central nervous system or psychiatric disorders or relevant neurological disorders besides polyneuropathy Diagnosis of sickle cell anemia or known chronic anemia History of chronic or relevant infections (for example human immunodeficieny virus (HIV), Hepatitis B) History of relevant allergy/hypersensitivity 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 Alcohol abuse, drug abuse Any laboratory value of clinical relevance that is outside an acceptable range Change of drug dosing of allowed co medication Any (electrocardiogram) ECG value outside the reference range and of clinical relevance. Fasted glucose >270 mg/dl or randomly determined blood glucose >400 mg/dl on two consecutive days during screening or wash out Serum creatinine above upper limit normal at screening

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: linagliptin<br>Pharmacokinetic (PK)/Pharmacodynamic (PD) investigation | Drug: linagliptin QD (once daily) for 7 days<br>* dipeptidyl peptidase IV (DPP-4) activity will be measured as PD response to drug administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Linagliptin: AUC_τ,ss | area under the concentration time curve (AUC_τ) of linagliptin in plasma at steady state over a uniform dosing interval | 24 hours | 
| Linagliptin: C_max,ss | maximum concentration of linagliptin in plasma at steady state | 24 hours | 
| 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. | One single measurement 24 h after drug administration under steady state conditions | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Emergent Adverse Events | Frequency of patients with AEs | 21 days | 
| 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 | 21 days | 
| 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 | 21 days | 
| 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 | 24 hours | 
| Linagliptin: C_max | maximum concentration of linagliptin in plasma on Day 1 | 24h | 
| 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. | One single measurement 24 h after drug administration |