Clinical trial NCT02261103: Bioavailability of Increasing Pramipexole Doses of Oral Extended Release (ER) Tablets in Healthy Male Volunteers
Official title: A Multiple Dose Study With Increasing Pramipexole Doses (0.375 mg to 4.5 mg q.d.) of Oral Extended Release (ER) Tablets With a Three-way Cross Comparison of 4.5 mg Pramipexole ER q.d. Fasted Versus 4.5 mg Pramipexole ER q.d. Fed Versus 1.5 mg Pramipexole Immediate Release Tablets t.i.d. Fasted in Healthy Male Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-10-10
Enrollment: 39
Sex: MALE
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The objectives of the studies are:

* To demonstrate similar total exposure between pramipexole ER fasted and pramipexole ER fed after multiple administration of the highest daily dose of 4.5 mg q.d. and to reveal any food effect leading to uncontrolled release
* To investigate the relative bioavailability of the ER-formulation of pramipexole in comparison to the IR-formulation at the highest daily dose of 4.5 mg after multiple dosing
* To demonstrate dose proportionality between the dose strengths of the pramipexole ER formulation of 0.375, 0.75, 1.5, 3.0, and 4.5 mg after multiple daily (q.d.) dosing


Eligibility criteria: Inclusion Criteria:

* All participants in the study should be healthy males
* Age range from 21 to 50 years
* Body mass index (BMI) be 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 (≤ one month 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 (\> 40 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

Primary outcomes:
measure: Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ=0-24h (AUC0-24,ss) for ER
timeFrame: up to 23 hours after drug application on day 5
measure: AUC0-24,ss for IR
timeFrame: up to 23 hours after drug application on day 5
measure: Maximum measured concentration of the analyte in plasma at steady state (Cmax)
timeFrame: up to 23 hours after drug application on day 5
measure: Area under the concentration-time curve of the analyte in plasma over the time interval 0 to 4h at steady state (AUC0-4,ss) for ER
timeFrame: up to 4 hours after drug application
Secondary outcomes:
measure: Minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmin,ss)
timeFrame: up to 23 hours after drug application on day 5
measure: Peak-Trough Fluctuation (PTF)
timeFrame: up to 23 hours after drug application on day 5
measure: Time from last dosing to the maximum concentration of the analyte in plasma at steady state over a uniform dosing interval τ (tmax,ss)
timeFrame: up to 23 hours after drug application on day 5
measure: Area under the concentration-time curve of the analyte in plasma over the time interval 0 to 8 h at steady state (AUC0-8,ss)
timeFrame: up to 8 hours after drug application
measure: Predose concentration of the analyte in plasma at steady state immediately before administration of the next dose (Cpre,ss)
timeFrame: predose on days 1 to 5
measure: Average concentration of the analyte in plasma at steady state (Cavg)
timeFrame: up to 23 hours after drug application on day 5
measure: Terminal half-life of the analyte in plasma at steady state (t1/2,ss)
timeFrame: up to 23 hours after drug application on day 5
measure: Mean residence time of the analyte in the body at steady state after p.o. administration (MRTpo,ss)
timeFrame: up to 23 hours after drug application on day 5
measure: Apparent clearance of the analyte in plasma at steady state after extravascular multiple dose administration (CL/F,ss)
timeFrame: up to 23 hours after drug application on day 5
measure: Renal clearance of the analyte at steady state determined over the dosing interval τ (CLR,ss)
timeFrame: up to 23 hours after drug application on day 5
measure: Apparent volume of distribution during the terminal phase λz at steady state following extravascular administration (Vz/F,ss)
timeFrame: up to 23 hours after drug application on day 5
measure: Amount of analyte that is eliminated in urine at steady state from the time point 0 to time point 24 (Ae0-24,ss)
timeFrame: up to 23 hours after drug application on day 5
measure: Amount of analyte that is eliminated in urine at steady state from the time point 0 to time point 8 (Ae0-8,ss) for IR
timeFrame: up to 8 hours after drug application on day 5
measure: Number of subjects with adverse events
timeFrame: up to 7 days after last drug administration
measure: Number of subjects with clinically relevant changes in vital signs
timeFrame: up to 7 days after last drug administration
measure: Number of subjects with clinically relevant changes in laboratory parameters
timeFrame: up to 7 days after last drug administration
measure: Assessment of global tolerability by investigator on a 4-point scale
timeFrame: day 5 of each visit
Other outcomes:
Locations:
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