Pharmacokinetics of Dipyridamole Administered as Aggrenox® (Dipyridamole Extended Release Plus Aspirin) Capsule Versus Dipyridamole Immediate Release Plus Aspirin Following Alteration of Stomach pH

Study Overview
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Brief Summary
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Comparison of pharmacokinetics of dipyridamole administered as Aggrenox versus dipyridamole administered as the immediate release formulation plus aspirin, under conditions of reduced stomach acidity.

Official Title
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Comparison of Pharmacokinetics of Dipyridamole Administered as Aggrenox® (Dipyridamole Extended Release Plus Aspirin) Capsule Versus Dipyridamole Immediate Release Plus Aspirin Following Alteration of Stomach pH by the Prior Administration of a Proton-pump Inhibitor: An Open-label 2-way Randomized Cross-over Study in Healthy Male and Female Subjects Age 40-65.

Conditions
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Healthy

Intervention / Treatment
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* Drug: Aggrenox
* Drug: Dipyridamole
* Drug: Aspirin
* Drug: Lansoprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects as determined by results of screening Signed written informed consent in accordance with Good Clinical Practice (GCP) and local legislation Age 40 - 65 years, inclusive, at time of Visit 1 Stomach pH > 4.0 on three consecutive measurements separated by at least five minutes, measured at Visits 3B and 5B prior to dosing with Aggrenox or dipyridamole-aspirin (DP-ASA) Exclusion Criteria: Any findings of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and considered by the investigator to be of clinical relevance Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders considered by the investigator to be of clinical relevance History of gastro-intestinal ulcer, perforation or bleeding Surgery of the gastro-intestinal tract (except appendectomy) Diseases of the central nervous system (such as epilepsy), neurological disorders, or psychiatric disorders Chronic or relevant acute infections. Screening tests will be performed for HIV, hepatitis B, and hepatitis C History of hypersensitivity to Aggrenox or any of the components or excipients Intake of drugs with a long dominant half-life (>24 hours) 1 month or less prior to Visit 1 Use of any drugs which might influence the results of the trial ten days or less prior to Visit 1 Participation in another trial with an investigational drug 1 month or less prior to Visit 1 Known alcohol abuse Known drug abuse (a drug screening test will be performed at Visits 1, 3, and 5) Blood donation 1 month or less prior to Visit 1 Excessive physical activities five days or less prior to Visit 1 History of hemorrhagic diathesis History of bronchial asthma Any laboratory value outside the reference range, considered by the investigator to be of clinical relevance For female subjects: Nursing Pregnancy Positive pregnancy test No adequate contraception (adequate contraception includes sterilization, intrauterine device, or oral contraceptives) Inability to maintain adequate contraception during the whole study period

Ages Eligible for Study
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Minimum Age: 40 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: Aggrenox<br>extended release | Drug: Aggrenox<br> <br> Drug: Lansoprazole<br> <br> |
| Active Comparator: dipyridamole+aspirin<br>immediate release | Drug: Dipyridamole<br> <br> Drug: Aspirin<br> <br> Drug: Lansoprazole<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 (AUC0-12) |  | up to 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| area under the concentration time curve 0-48 hours (AUC0-48) |  | up to 48 hours | 
| area under the concentration time curve extrapolated to infinity (AUC0-inf) |  | up to 3 days | 
| maximum observed plasma concentration (Cmax) |  | up to 3 days | 
| time to maximum observed plasma concentration (Tmax) |  | up to 3 days | 
| terminal half life (t1/2) |  | up to 3 days | 
| number of subjects with adverse events |  | up to 3 weeks | 
| number of subjects with clinically significant changes in laboratory findings |  | up to 17 days |