Bioavailability of Different Pramipexole Slow-release Formulations Compared to Immediate-release Tablet in Healthy Male Volunteers

Study Overview
=================
Brief Summary
-----------------
Study to compare the oral bioavailability of seven prototype slow-release formulations to immediate-release tablets

Official Title
-----------------
A Multiple Dose Seven-way Cross-over Formulation-finding Study Comparing the Oral Bioavailability of Seven Prototype Slow-release Formulations With 0.75 mg Pramipexole (Four Days Each) to Immediate-release Tablets at Steady State in Healthy Male Volunteers

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Formulation B: Pramipexole Slow release (SR) tablet
* Drug: Formulation C: Pramipexole Slow release tablet
* Drug: Formulation D: Pramipexole Slow release tablet
* Drug: Formulation E: Pramipexole Slow release tablet
* Drug: Formulation F: Pramipexole Slow release tablet
* Drug: Formulation G: Pramipexole Slow release tablet
* Drug: Formulation H: Pramipexole Slow release tablet
* Drug: Pramipexole immediate release (IR) tablets


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All participants in the study should be healthy males Participants should be ranging from 21 to 50 years of age Body mass index (BMI) within 18.5 to 29.9 kg/m2 In accordance with Good Clinical Practice and the local legislation all volunteers will have given their written informed consent prior to admission to the study Exclusion Criteria: 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 Hypersensitivity to pramipexole, or other dopamine agonists Supine blood pressure at screening of systolic < 110 mmHg and diastolic < 60 mmHg A haemoglobin value at screening of less than 13.5 g/dl (usual lower limit of normal for males: 12.6 g/mL) Subjects involved in passenger transport or operation of dangerous machines

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Formulation B<br>Slow release (SR) tablet | Drug: Formulation B: Pramipexole Slow release (SR) tablet<br> <br> |
| Experimental: Formulation C<br>SR tablet | Drug: Formulation C: Pramipexole Slow release tablet<br> <br> |
| Experimental: Formulation D<br>SR tablet | Drug: Formulation D: Pramipexole Slow release tablet<br> <br> |
| Experimental: Formulation E<br>SR tablet | Drug: Formulation E: Pramipexole Slow release tablet<br> <br> |
| Experimental: Formulation F<br>SR tablet | Drug: Formulation F: Pramipexole Slow release tablet<br> <br> |
| Experimental: Formulation G<br>SR tablet | Drug: Formulation G: Pramipexole Slow release tablet<br> <br> |
| Experimental: Formulation H<br>SR tablet | Drug: Formulation H: Pramipexole Slow release tablet<br> <br> |
| Active Comparator: immediate release (IR) formulation<br> | Drug: Pramipexole immediate release (IR) tablets<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma total exposure (AUCτ,ss) |  | up to 168 hours after each drug administration | 
| Urine total exposure (Aeτ,ss) |  | up to 168 hours after each drug administration | 
| Plasma maximum exposure (Cmax,ss) |  | up to 168 hours after each drug administration | 
| Plasma minimum exposure (Cmin,ss) |  | up to 168 hours after each drug administration | 
| Plasma average concentration (Cavg) |  | up to 168 hours after each drug administration | 
| Plasma peak to trough fluctuation (PTF) |  | up to 168 hours after each drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-6,11 for the immediate release (IR) formulation |  | day 7 of visit 2 | 
| Cmax for the IR formulation |  | up to 168 hours after drug administration in visit 2 | 
| Cmin for the IR formulation |  | up to 168 hours after drug administration in visit 2 | 
| tmax for the IR formulation |  | up to 168 hours after drug administration in visit 2 | 
| Urinary excretion (Ae) for the IR formulation |  | up to 168 hours after drug administration in visit 2 | 
| tmax,4 for the SR formulation |  | up to 96 hours after drug administration in visit 3-5, 7 and 9 | 
| t1/2,4 for the SR formulation |  | up to 96 hours after drug administration in visit 9 | 
| Urinary excretion (Ae) for the SR formulation |  | up to 168 hours after drug administration | 
| Number of subjects with adverse events |  | up to 8 days after last drug administration | 
| Number of subjects with clinically significant findings in laboratory tests |  | up to 8 days after last drug administration | 
| Number of subjects with clinically significant findings in vital signs | blood pressure, pulse rate | up to 8 days after last drug administration | 
| Assessment of global tolerability by investigator on a 5-point scale |  | at the end of each of the visits 2 to 9 |