Study to Compare the Pharmacokinetics of Dipyridamole in Three Different Asasantin Extended Release (ER) Formulations in Healthy Male and Female Volunteers

Study Overview
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Brief Summary
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Comparative pharmacokinetics of dipyridamole in two new formulations of Asasantin ER compared to the present commercial formulation

Official Title
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A Double-blind, Randomised, 3-way Cross-over Study to Compare the Pharmacokinetics of Dipyridamole in Three Different Asasantin ER Extended Release (ER) 200 mg Dipyridamole/25 mg ASA Formulations in Healthy Male and Female Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Asasantin ER, new formulation I
* Drug: Asasantin ER, new formulation II
* Drug: Asasantin ER, present commercial formulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All participants in the study should be healthy males or females, range from 21 to 50 years of age and be within ± 20 % of their normal weight (Broca-Index) Prior to admission to the study all volunteers will have given, in accordance with good clinical practice (GCP) and the local legislation, their written informed consent Subsequently each subject will have his medical history taken and will receive a complete medical examination (incl. blood pressure and pulse rate measurements) as well as a 12-lead ECG Hematopoietic, hepatic and renal function tests will be carried out in the laboratory The subjects will fast for 12 hours before collection of specimens for all laboratory evaluations The above mentioned examinations will be performed within 14 days before the first administration of the test substance Exclusion Criteria: Volunteers are excluded from the study if the results of the medical examination or laboratory tests are judged by the clinical investigator to differ significantly from normal clinical values Subjects with known gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Subjects with diseases of the central nervous system (such as epilepsy) or with psychiatric or neurological disorders History of orthostatic hypotension, fainting spells or blackouts Subjects with chronic or relevant acute infections Subjects with allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator Volunteers who have taken a drug with a long half-life (≥ 24 hours) within one month or less than ten half-lives of the respective drug before enrolment in the study Volunteers who receive any other drugs which might influence the results of the trial during the week previous to enrolment in the study Volunteers who participate in another study with an investigational drug within the last two months preceding the study Volunteers who are unable to refrain from smoking on study days Volunteers who smoke more than10 cigarettes (or equivalent) per day Volunteers who drink more than 60 g of alcohol per day Volunteers who are dependent on drugs Volunteers who donate blood (≥ 100 mL) within the last four weeks Volunteers who participate in excessive physical activities within the last week before the study (e.g. competitive sports) Volunteers who suffer from any other disease or abnormality of clinical relevance History of hemorrhagic diatheses History of gastro-intestinal ulcer, perforation or bleeding History of bronchial asthma History of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency Female subjects: Pregnancy Positive pregnancy test No adequate contraception (adequate contraception e.g. sterilization, intrauterine devices (IUD), oral contraceptives) Inability to maintain this adequate contraception during the whole study period Lactation period

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Asasantin ER, new formulation I<br> | Drug: Asasantin ER, new formulation I<br> <br> |
| Experimental: Asasantin ER, new formulation II<br> | Drug: Asasantin ER, new formulation II<br> <br> |
| Active Comparator: Asasantin ER, present commercial formulation<br> | Drug: Asasantin ER, present commercial formulation<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 dipyridamole in plasma at steady state (AUC,ss) |  | Up to 48 hours after start of drug administration | 
| Percent peak trough fluctuation of dipyridamole in plasma (%PTF) |  | Up to 48 hours after start of drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration of the analytes in plasma at steady state (Cmax,ss) |  | Up to 48 hours after start of drug administration | 
| Minimum measured concentration of the analytes in plasma at steady state over a uniform dosing interval τ (Cmin,ss) |  | Up to 48 hours after start of drug administration | 
| Time from dosing to the maximum measured concentration of the analytes in plasma at steady state over a uniform dosing interval τ Time from dosing to the maximum measured concentration of the analytes in plasma at steady state (tmax,ss) |  | Up to 48 hours after start of drug administration | 
| Percent area under the curve fluctuation of the analytes in plasma (AUCfluct) |  | Up to 48 hours after start of drug administration | 
| Terminal half-life of the analytes in plasma (t1/2) |  | Up to 48 hours after start of drug administration | 
| Percent of dose of the analytes recovered unchanged in urine (Ae%) |  | Up to 24 hours after start of drug administration | 
| Ratio of peak concentration of the analytes in plasma over area under the curve at steady state (Cmax,ss / AUC,ss) |  | Up to 48 hours after start of drug administration | 
| Number of subjects with clinically relevant changes in vital signs (blood pressure, pulse rate) |  | up to 8 days after last study drug administration | 
| Number of subjects with clinically relevant changes in 12-lead ECG |  | up to 8 days after last study drug administration | 
| Number of subjects with clinically relevant changes in laboratory values |  | up to 8 days after last study drug administration | 
| Number of subjects with adverse events |  | up to 8 days after last study drug administration |