Bioequivalence of a New Asasantin Formulation Extended Release (ER) Compared to the Commercially Available Asasantin Formulation (Aggrenox®; Extended Release) in Healthy Male and Female Volunteers

Study Overview
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Brief Summary
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Study to establish the bioequivalence of a new formulation of Asasantin ER compared to the present commercially available Asasantin ER formulation (Aggrenox®)

Official Title
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Bioequivalence of a New Asasantin Capsule Formulation (Extended Release Combination 200 mg Dipyridamole/25 mg ASA) Compared to the Commercially Available Asasantin Capsule Formulation (Aggrenox®; Extended Release Combination 200 mg Dipyridamole/25 mg ASA) Following Multiple Oral Administration at Steady State After a run-in Phase (Persantine ER BID for 2 Days Each: 25 mg, 50 mg, 100 mg, 150 mg [Persantine®]; 200 mg Dipyridamole/25 mg ASA [Asasantin ER])- an Open Label, Randomized, Multiple-dose, Two-way Crossover, Change-over Study in Healthy Male and Female Volunteers

Conditions
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Healthy

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Based upon a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead ECG, clinical laboratory tests: No finding deviating from normal and of clinical relevance No evidence of a clinically relevant concomitant disease Age ≥ 21 and ≤ 65 years Body mass index (BMI) ≥ 18.5 and ≤ 29.9 kg/m2 Signed and dated written informed consent prior to admission to the study in accordance with good clinical practice (GCP) and the local legislation Able to communicate well with the investigator and to comply with study requirements Exclusion Criteria: Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Surgery of gastrointestinal tract (except appendectomy) Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders History of relevant orthostatic hypotension, fainting spells or blackouts Chronic or relevant acute infections History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 14 days prior to administration or during the trial Participation in another trial with an investigational drug within two months prior to administration or during the trial Smoker (more than 10 cigarettes or 3 cigars or 3 pipes/day) Inability to refrain from smoking on trial days Alcohol abuse (more than 60 g/day) Drug abuse Blood donation (more than 100 mL within four weeks prior to administration or during the trial) Excessive physical activities (within one week prior to administration or during the trial) Any laboratory value outside the reference range that is of clinical relevance Inability to comply with dietary regimen of study centre History of frequent headaches History of gastro-intestinal ulcer disease For female subjects: Pregnancy Positive pregnancy test No adequate contraception e.g. oral contraceptives, sterilization, intrauterine device (IUD) 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: 65 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Asasantin ER, new formulation<br> | Drug: Asasantin ER, new formulation<br> <br> |
| Active Comparator: Asasantin ER, present commercial formulation<br> | Drug: Asasantin ER, present commercial formulation<br> <br> * Other names: Aggrenox®;|

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 over one dosing interval at steady state (AUCτ,ss) |  | up to 17 days | 
| Maximum measured concentration of dipyridamole in plasma at steady state (Cmax,ss) |  | up to 17 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minimum measured concentration of dipyridamole in plasma at steady state (Cmin,ss) |  | up to 17 days | 
| Average concentration of dipyridamole in plasma at steady state (Cavg) |  | up to 17 days | 
| Time from dosing to the maximum concentration of dipyridamole in plasma at steady state (tmax,ss) |  | up to 17 days | 
| Peak trough fluctuation of dipyridamole in plasma (PTF) |  | up to 17 days | 
| Amount of the analytes that were eliminated in urine (Ae) |  | up to 24 hours after drug administration | 
| Fraction in percent of dose of the analytes that was eliminated in urine (fe) |  | up to 24 hours after drug administration | 
| Number of subjects with clinically significant changes in 12-lead ECG |  | up to 17 days | 
| Number of subjects with clinically significant changes in vital signs (blood pressure, pulse rate) |  | up to 17 days | 
| Number of subjects with clinically significant changes in laboratory tests |  | up to 17 days | 
| Number of subjects with adverse events |  | up to 17 days | 
| Assessment of tolerability by the investigator on a 4-point scale |  | after 17 days |