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

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

Study to compare the oral bioavailability of seven prototype slow-release formulations to immediate-release tablets

Study Overview

• Status: Completed
• 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

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

8

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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
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
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 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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: June 1, 2004
• Primary Completion (Actual): September 1, 2004

Study Registration Dates

• First Submitted: October 9, 2014
• First Submitted That Met QC Criteria: October 9, 2014
• First Posted (Estimate): October 10, 2014

Study Record Updates

• Last Update Posted (Estimate): October 10, 2014
• Last Update Submitted That Met QC Criteria: October 9, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; Dopamine Agonists; Dopamine Agents; Antioxidants; Antiparkinson Agents; Anti-Dyskinesia Agents; Pramipexole
• Other Study ID Numbers: 248.529