Drug-drug Interaction Study of Aggrenox and Omeprazole in Normal Volunteers

Study Overview
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Brief Summary
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The objective of the current study is to investigate if a drug-drug interaction occurs with the administration of omeprazole 80 mg q.d. at steady state on the pharmacokinetics of dipyridamole and the pharmacodynamics of ASA-induced platelet aggregation inhibition (components of Aggrenox®) when administered every 12 hours at steady state.

Detailed Description
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Purpose:

Official Title
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Drug-drug Interaction Study of the Effect of Omeprazole 80 mg q.d. at Steady State on the Pharmacokinetics and Pharmacodynamics of Aggrenox® Every 12 Hours at Steady State in Healthy Male and Female Volunteers (an Open-label, Randomised, Crossover Study)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Aggrenox alone
* Drug: Aggrenox and omeprazole
* Drug: Aggrenox and omeprazole
* Drug: Omeprazole alone


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy males and females according to the following 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 BMI >18.5 and BMI <32 kg/m2 (Body Mass Index) Exclusion criteria: Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance in the opinion of the PI Any evidence of a clinically relevant concomitant disease Clinically significant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, hormonal, or hematologic (including a history of abnormal bruising) disorders in the opinion of the PI Surgery of the gastrointestinal tract that might impair drug absorption Clinically significant 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 relevant allergy/hypersensitivity (including allergy to study drugs or its excipients, or reactions to related drugs [e.g., non-steroidal anti-inflammatory drugs]) Intake of drugs with a long half-life (¿24 hours) within one month, or less than 10 half lives of the respective drug, prior to study drug administration or during the trial Use of drugs which might reasonably influence the results of the trial (including OTC antacids) 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 Tobacco use within the 90 days prior to check-in and throughout the study Alcohol abuse within the past 2 years Drug abuse within the past 2 years Blood donation or other significant blood loss within 56 days (inclusive) prior to screening, or plasma donation within 7 days (inclusive) prior to study drug administration, or during the trial Excessive physical activities (within one week prior to first drug administration or during the trial) Any laboratory value outside the reference range that is of clinical relevance in the opinion of the PI; including positive virology, or urine drug screen, or positive fecal occult blood test Inability to comply with dietary regimen of trial site In the opinion of the investigator it would be in the best interest of the subject to be excluded from participation.

Ages Eligible for Study
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Minimum Age: 18 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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment A<br>Aggrenox alone | Drug: Aggrenox alone<br>* Aggrenox 1 capsule twice daily for 7 days<br>|
| Experimental: Treatment B<br>Aggrenox and omeprazole | Drug: Aggrenox and omeprazole<br>* Aggrenox 1 capsule twice daily and omeprazole 80mg once daily for 7 days<br>|
| Active Comparator: Treatment C<br>Omeprazole alone | Drug: Omeprazole alone<br>* omeprazole 80 once daily for 7 days<br>|
| Experimental: Treatment D<br>Aggrenox and omeprazole | Drug: Aggrenox and omeprazole<br>* Aggrenox 1 capsule twice daily and omeprazole 80mg once daily for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Dipyridamole Maximum Concentration (Cmax) | Maximum measured concentration of dipyridamole in plasma | 7 days | 
| Plasma Dipyridamole Area Under Plasma Concentration-time Curve From Zero to 12 Hours (AUC0-12) | Area under the concentration time curve of the analyte in plasma from 0 to 12 hours at steady state | 7 days | 
| Inhibition of Platelet Aggregation at 4 Hours Post Dose (IPA4) | IPA4 equals the platelet aggregation measured 4 hours post dose divided by the platelet aggregation measured at baseline (multiplied by 100). | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Dipyridamole Minimum Concentration (Cmin) | Minimum measured concentration of dipyridamole in plasma | 7 days | 
| Inhibition of Platelet Aggregation at 12 Hours Post Dose (IPA12) | IPA12 equals the platelet aggregation measured 12 hours post dose divided by the platelet aggregation measured at baseline (multiplied by 100). | 7 days | 
| Percentage Peak-to-trough Fluctuation (%PTF) | PTF = 100*((Cmax-Cmin)/Cavg) where Cavg=(AUC0-12)/12. | 7 days |