In Vitro/in Vivo Correlation (IVIVC) for Oral Slow Release (SR) Tablets Pramipexole in Healthy Male Volunteers

Study Overview
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Brief Summary
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The primary objective of the study was to estimate the magnitude of the error in the prediction of in vivo bioavailability (AUC0-30,Cmax) by means of in vitro dissolution data applying the methods of IVIVC. The secondary objective of the study was to investigate whether the intake of food 30 minutes prior to drug administration affects the systemic exposure of pramipexole SR C2 or not

Official Title
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A Single Dose Five-way Cross-over Study to Establish an in Vitro/in Vivo Correlation (IVIVC) for Oral Slow Release (SR) Tablets With 0.375 mg Pramipexole in Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Other: High fat, high caloric meal
* Drug: Pramipexole IR tablets
* Drug: Pramipexole SR C
* Drug: Pramipexole SR C2
* Drug: Pramipexole SR C2A
* Drug: Pramipexole SR C2B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects as determined by results of the screening Signed written informed consent in accordance with Good Clinical Practice (GCP) and local legislation Age ≥ 18 and ≤ 50 years BMI ≥ 18.5 and ≤ 29.9 kg/m2 Exclusion Criteria: Hypersensitivity to pramipexole or to other dopamine agonists Supine systolic blood pressure lower than 110 mmHg and supine diastolic blood pressure lower than 60 mmHg at screening Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 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 is deemed relevant to the trial as judged by the investigator Intake of drugs with a long half-life (> 24:00 hours) within at least one month or less than ten half-lives of the respective drug before enrolment in the study or during the study Use of any drugs which might influence the results of the trial up to 7 days prior to enrolment in the study or during the study Participation in another trial with an investigational drug (≤ two months prior to administration or during the trial) Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day) Inability to refrain from smoking on in-house trial days Alcohol abuse (> 60 g/day) Drug abuse Blood donation (≥ 100 mL within four weeks prior to administration or during the trial) Any laboratory value outside the clinically accepted reference range Excessive physical activities within the last week before the trial or during the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

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 |
| --- | --- |
| Active Comparator: Pramipexole IR<br> | Drug: Pramipexole IR tablets<br> <br> |
| Experimental: Pramipexole SR C2 in the fasted state<br> | Drug: Pramipexole SR C2<br> <br> |
| Experimental: Pramipexole SR C2A in the fasted state<br> | Drug: Pramipexole SR C2A<br> <br> |
| Experimental: Pramipexole SR C2B in the fasted state<br> | Drug: Pramipexole SR C2B<br> <br> |
| Experimental: Pramipexole SR C in the fasted state<br> | Drug: Pramipexole SR C<br> <br> |
| Experimental: Pramipexole SR C2 in the fed state<br> | Other: High fat, high caloric meal<br> <br> Drug: Pramipexole SR C2<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-30 (area under the concentration time curve of pramipexole in blood plasma over the time interval 0 to 30 h after drug administration) |  | Up to 30 hours after drug administration | 
| Cmax (maximum measured concentration of pramipexole in blood plasma) |  | Up to 30 hours after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-10 (area under concentration-time curve of pramipexole in blood plasma over the time interval from 0 to the median tmax in the fasted state) |  | Up to 30 hours after drug administration | 
| AUC0-24 (area under concentration-time curve of pramipexole in blood plasma over the time interval from 0 to 24 h after drug administration), |  | Up to 24 hours after drug administration | 
| AUC0-∞ (area under the concentration-time curve of pramipexole in blood plasma over the time interval from 0 extrapolated to infinity), |  | Up to 30 hours after drug administration | 
| tmax (time from dosing to the maximum concentration of pramipexole in blood plasma) |  | Up to 30 hours after drug administration | 
| λz (terminal rate constant in blood plasma), |  | Up to 30 hours after drug administration | 
| t½ (terminal half-life of pramipexole in blood plasma) |  | Up to 30 hours after drug administration | 
| MRTpo (mean residence time of pramipexole in the body after oral administration) |  | Up to 30 hours after drug administration | 
| CL/F (apparent clearance of pramipexole in the blood plasma after extravascular administration) |  | Up to 30 hours after drug administration | 
| Vz/F (apparent volume of distribution during the terminal phase (λz) following an extravascular dose) |  | Up to 30 hours after drug administration | 
| Aet1-t2 (amount of analyte that is eliminated in urine from the time point t1 to time point t2) |  | Up to 120 hours after drug administration | 
| Number of subjects with adverse events |  | Up to 7 days after last drug administration | 
| Number of subjects with clinically significant findings in vital signs | pulse rate, blood pressure | Up to 7 days after last drug administration | 
| Number of subjects with clinically significant findings in laboratory parameters |  | Up to 7 days after last drug administration | 
| Number of subjects with clinically significant findings in physical examination |  | Up to 7 days after last drug administration |