Study to Evaluate Pharmacokinetics of Dipyridamole in Three New Formulations of Asasantin ER in Healthy Female and Male Subjects

Study Overview
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Brief Summary
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The objective of this study was to compare the pharmacokinetics of dipyridamole in three different Asasantin ER batches (test) containing different amounts of retarding lacquers to the existing commercial product at steady state with b.i.d. treatment

Official Title
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Bioavailability of Dipyridamole After Asasantin (Extended Release 200mg Dipyridamole/25mg ASA) in 3 Experimental Formulations (Given b.i.d. Over 3 or 5 Days, Respectively) Relative to the Standard Formulation in 16 Healthy Female and Male Subjects. Intraindividual Comparison, Randomised, Open

Conditions
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Healthy

Intervention / Treatment
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* Drug: Asasantin ER (new formulation - low)
* Drug: Asasantin ER (new formulation - medium)
* Drug: Asasantin ER (new formulation - high)
* Drug: Asasantin ER - commercial formulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subjects as determined by results of screening Signed written informed consent in accordance with Good Clinical Practice (GCP) and local legislation Female subjects are not lactating. Females must use adequate contraception (adequate contraception e.g. sterilization, IUP, oral contraceptives) prior to administration of study medication, during the study until after release from the study. Women must have negative blood pregnancy tests Age >= 18 and <= 60 years BMI >=18.5 and <=29.9 kg/m2 (see abbreviations for formula) Able to communicate well with the investigator and to comply with study requirements Laboratory values within a clinically defined reference range Exclusion Criteria: Any finding of the medical examination (including blood pressure, pulse rate, and electrocardiogram) deviating from normal and of clinical relevance Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic 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 orthostatic hypotension, fainting spells or blackouts Chronic or relevant acute infections History of allergy/hypersensitivity (including drug allergy) which were deemed relevant to the trial as judged by the investigator Intake of drugs with a long half-life (> 24 hours) (< 1 month prior to administration or during the trial) Use of any drugs, which might influence the results of the trial, (< 10 days prior to administration or during the trial) Participation in another trial with an investigational drug (< 1 months prior to administration (at least 10 times the relevant elimination half-life) or during trial) Having had prescription medication 2 weeks prior to study drug administration or over the counter medication 1 week prior to study drug administration (at least 10 times the relevant elimination half-life) Smoker (> 10 cigarettes or 3 cigars or 3 pipes/day) Alcohol abuse (> 60 g/day) Drug abuse Use of methylxanthine-containing drinks or foods (coffee, tea, cola, energy drinks, chocolate, etc.), grapefruit or grapefruit juice, alcohol, green tea, or tobacco < 5 days prior to administration of study drug Blood donation or loss > 400 mL (< 1 month prior to administration or during the trial) Excessive physical activities (< 5 days prior to administration or during the trial) Any ECG value outside of the reference range of clinical relevance including, but not limited to QTcB > 480 ms or QRS interval > 110 ms History of any familial bleeding disorder Inability to comply with dietary regimen of study centre Inability to comply with investigator's instructions For Female Subjects: Pregnancy Positive pregnancy test No adequate contraception (adequate contraception e.g. sterilization, Intrauterine Pessary (IUP), oral contraceptives) Inability to maintain this adequate contraception during the whole study period Lactation period During the interval between screening and start of drug administration tobacco and caffeine are restricted to avoid withdrawal when starting medication. As no relevant influence on Pharmacokinetic parameters is known moderate tobacco and caffeine consumption are allowed to facilitate trial participation (up to 10 cigarettes or 3 cigars or 3 pipes/day, and/or up to three cups of coffee respectively). Ovarian hormone substitution and oral contraception are allowed to be continued during the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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 - low)<br> | Drug: Asasantin ER (new formulation - low)<br> <br> |
| Experimental: Asasantin ER (new formulation - medium)<br> | Drug: Asasantin ER (new formulation - medium)<br> <br> |
| Experimental: Asasantin ER (new formulation- high)<br> | Drug: Asasantin ER (new formulation - high)<br> <br> |
| Active Comparator: Asasantin ER - commercial formulation<br> | Drug: Asasantin ER - commercial formulation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary excretion of dipyridamole | geometric means of percentage of amount excreted from time zero to 10 h (% Ae 0-10h) | day 2, day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax urine (Maximum measured concentration of the analyte) | Urine collected fraction from 0 -3 hours as surrogate for Cmax | 0 to 3 hours after drug intake | 
| Cmin (Minimum measured concentration of the analyte) | Urine collected fraction from 8 - 10 hours as surrogate for Cmin | 8 - 10 hours after drug intake | 
| % PTF urine (peak trough fluctuation) | Estimated from the difference of percentage amount excreted from 1 - 3 hours (%Ae (1-3hours) and %Ae (8-10 hours) divided by the average excretion rate over the total dosing interval | Up to 10 hours after drug intake | 
| Number of subjects with adverse events |  | up to 1 month |