Influence of Pantoprazole on the Pharmacokinetics of Fradafiban After Multiple Oral Doses of Lefradafiban in Healthy Subjects

Study Overview
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Brief Summary
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Study to assess the absorption of 20 mg Lefradafiban in two formulations, each under physiological conditions and with 40 mg Pantoprazole

Official Title
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Influence of 40 mg Pantoprazole Per Day on the Pharmacokinetics of Fradafiban After Multiple Oral Doses of 20 mg Lefradafiban Tid as Acid Free Tablet and Sachet Over 5 Days in Healthy Subjects. A 4-way Crossover Randomized Open Trial.

Conditions
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Healthy

Intervention / Treatment
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* Drug: Lefradafiban tablet
* Drug: Pantoprazole tablet
* Device: Lefradafiban double chamber sachet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects as determined by results of screening Signed written informed consent in accordance with good clinical practice (GCP) and local legislation Age ≥ 18 and ≤ 60 years, planned stratification: age < 40 years (4 subjects) and ≥ 40 years (8 subjects) Broca ≥ - 20 % and ≤ + 20 % Exclusion Criteria: Use of any drugs which might influence the results of the trial within 10 days prior to administration or during the trial Intake of drugs with a long half-life (> 24 hours) within 1 month prior to administration Participation in another trial with an investigational drug within 2 months prior to administration or during the trial Drug abuse Alcohol abuse (> 60 g/day) Smoker (> 10 cigarettes or 3 cigars or 3 pipes/day) or inability to refrain from smoking on study days Excessive physical activities within 5 days prior to administration or during the trial Blood donation within 1 month prior to administration or during the trial History or current gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, hormonal disorders Chronic or relevant acute infections Diseases of the central nervous system (such as epilepsy) or psychiatric disorders History of Allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator Any bleeding disorder including prolonged or habitual bleeding Other hematologic disease Cerebral bleeding (e.g. after a car accident) Recent surgical procedures Thrombocytes < 150000/µ Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance Any laboratory value outside the clinically accepted reference range Other disease or abnormality of clinical relevance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lefradafiban tablet with Pantoprazole<br> | Drug: Lefradafiban tablet<br> <br> Drug: Pantoprazole tablet<br> <br> |
| Active Comparator: Lefradafiban tablet without Pantoprazole<br> | Drug: Lefradafiban tablet<br> <br> |
| Experimental: Lefradafiban double chamber sachet with Pantoprazole<br> | Drug: Pantoprazole tablet<br> <br> Device: Lefradafiban double chamber sachet<br> <br> |
| Active Comparator: Lefradafiban double chamber sachet without Pantoprazole<br> | Device: Lefradafiban double chamber sachet<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve of the analyte in plasma at steady state, 13th dosing interval (AUCss,13) |  | Up to 168 hours after first drug administration | 
| Maximum concentration of the analyte in plasma at steady state, 13th dosing interval (Cmax,ss,13) |  | Up to 168 hours after first drug administration | 
| Pre-dose concentration of the analyte in plasma at steady state, 13th dosing interval (Cpre,ss,13) |  | Up to 168 hours after first drug administration | 
| Amount of the analyte eliminated unchanged in the urine per dosing interval (Ae% (i=1,...,13)) |  | Up to 168 hours after first drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre-dose concentration lf the analyte in plasma for the i-th dosing interval (Cpre,i (i=1,4,7,10,11,12)) |  | Up to 168 hours after first drug administration | 
| Plasma concentration of the analyte at 2 hours post-dose for the i-th dosing interval (C2h,i (i=10,11,12)) |  | up to 2 hours after each dosing interval | 
| Terminal half life of the analyte in plasma (t1/2) |  | Up to 168 hours after first drug administration | 
| Percent swing of peak/trough concentrations of the analyte in plasma for the i-th dosing interval (%Swing,i) | Calculated: (C2h,i - Cpre,i) / Cpre,i * 100% (i=10,11,12) | Up to 168 hours after first drug administration | 
| Percent peak-trough fluctuation for the 13th dosing interval (%PTF13) | Calculated: (Cmax,ss,13 - Cpre,ss,13) * 8h / AUCss,13 * 100%) | Up to 168 hours after first drug administration | 
| Percent fluctuation of area under the plasma concentration-time curve (AUCfluc,13) | Calculated: (AUCabove,13 - AUCbelow,13) / AUCabove,13 | Up to 168 hours after first drug administration | 
| Fibrinogen receptor occupancy levels |  | Up to 168 hours after first drug administration | 
| Number of subjects with adverse events |  | Up to 3 days after last drug administration | 
| Number of subjects with clinically significant findings in vital signs | systolic and diastolic blood pressure, pulse rate | Up to 3 days after last drug administration | 
| Number of subjects with clinically significant findings in laboratory tests |  | Up to 3 days after last drug administration |