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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Pramipexole IR tablets; Drug: Pramipexole SR C2; Drug: Pramipexole SR C2A; Drug: Pramipexole SR C2B; Drug: Pramipexole SR C; Other: High fat, high caloric meal

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Pramipexole IR	Drug: Pramipexole IR tablets
EXPERIMENTAL: Pramipexole SR C2 in the fasted state	Drug: Pramipexole SR C2
EXPERIMENTAL: Pramipexole SR C2A in the fasted state	Drug: Pramipexole SR C2A
EXPERIMENTAL: Pramipexole SR C2B in the fasted state	Drug: Pramipexole SR C2B
EXPERIMENTAL: Pramipexole SR C in the fasted state	Drug: Pramipexole SR C
EXPERIMENTAL: Pramipexole SR C2 in the fed state	Drug: Pramipexole SR C2; Other: High fat, high caloric meal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (ACTUAL): December 1, 2005

Study Registration Dates

• First Submitted: October 7, 2014
• First Submitted That Met QC Criteria: October 7, 2014
• First Posted (ESTIMATE): October 9, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): October 9, 2014
• Last Update Submitted That Met QC Criteria: October 7, 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: 248.560