Multiple Dose Bioequivalence Study of Pramipexole Extended Release in Chinese Healthy Male Volunteers

A Multiple Dose Bioequivalence Study of Pramipexole With Increasing Doses (0.375mg to 1.5mg q.d.) of Oral Extended Release (ER) Tablet in Two-way Cross-over Comparison of 0.375mg Extended Release Tablet q.d. Versus 0.125mg Immediate Release (IR) Tablet t.i.d and 1.5 mg Extended Release Tablet q.d. Versus 0.5mg Immediate Release Tablet t.i.d. in Chinese Healthy Male Volunteers

To establish bioequivalence at steady state of:

1)0.375 mg pramipexole extended release tablet q.d. in fasted status versus 0.125 mg pramipexole Immediate release tablet t.i.d. in fasted status 2)1.5 mg pramipexole extended release tablet q.d. in fasted status versus 0.5 mg pramipexole Immediate release tablet t.i.d. in fasted status

To investigate dose proportionality of pharmacokinetics parameters for:

1)pramipexole extended release dosage of 0.375 to 1.5 mg q.d.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: pramipexole extended release; Drug: pramipexole immediate release

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • 248.665.86002 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion criteria:

1. Healthy males according to the following criteria:

   Based upon a complete medical history, including the physical examination, vital signs (blood pressure, pulse rate), 12-lead electrocardiogram, clinical laboratory tests

2. Age older than or equal 18 and Age younger than or equal 40 years
3. Body Mass Index larger than or equal 19 and Body Mass Index less than or equal 24kg/m2
4. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation.

Exclusion criteria:

1. Any finding of the medical examination (including Pulse Rate and electrocardiogram) deviating from normal and of clinical relevance
2. Any evidence of a clinically relevant concomitant disease
3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
4. Surgery of the gastrointestinal tract (except appendectomy)
5. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
6. History of relevant orthostatic hypotension, fainting spells or blackouts.
7. Chronic or relevant acute infections
8. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
9. Intake of drugs with a long half-life (longer than 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
10. Use of drugs which might reasonably influence the results of the trial up to 7 days before the start of drug administration in the study or during the study period
11. Participation in another trial with an investigational drug within one months prior to administration or during the trial
12. Smoker (more than 10 cigarettes or more than 3 cigars or more than 3 pipes/day)
13. Inability to refrain from smoking on trial days
14. Alcohol abuse (more than 40 g/day)
15. Drug abuse
16. Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
17. Excessive physical activities (within one week prior to administration or during the trial)
18. Any laboratory value outside the reference range that is of clinical relevance

19. Any positive results in hepatitis B surface antigen (HBsAg), anti hepatitis B core (HBc) antibodies, anti hepatitis C virus (HCV) antibodies and human immunodeficiency virus (HIV) test

    Exclusion criteria specific for this study:

20. Hypersensitivity to pramipexole or other dopamine agonists
21. Supine blood pressure at screening of systolic<100 mmHg and diastolic < 60 mmHg, or symptomatic orthostatic hypotension (i. .e. clinical symptoms of orthostatic hypotension associated with a decline >=20 mmHg in systolic BP and a decline >=10 mmHg in diastolic BP, at one minute after standing compared to the previous supine systolic and diastolic BP obtained after 5 minutes of quiet rest)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: pramipexole extended release; 0.375mg once per day for 5 days (cross-over), 0.75mg once per day for 5 days (up-titration), 1.5mg once per day for 5 days (cross-over)	Drug: pramipexole extended release; 0.375mg once per day for 5 days (cross-over), 0.75mg once per day for 5 days (up-titration), 1.5mg once per day for 5 days (cross-over); Drug: pramipexole immediate release; 0.125mg three times a day for 5 days (crossover), 0.5mg three times a day for 5 days (cross over)
Active Comparator: pramipexole immediate release; 0.125mg three times a day for 5 days (crossover), 0.5mg three times a day for 5 days (cross over)	Drug: pramipexole extended release; 0.375mg once per day for 5 days (cross-over), 0.75mg once per day for 5 days (up-titration), 1.5mg once per day for 5 days (cross-over); Drug: pramipexole immediate release; 0.125mg three times a day for 5 days (crossover), 0.5mg three times a day for 5 days (cross over)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve of Pramipexole in Plasma at Steady State Over 24 Hours (AUC0-24,ss); in Case of ER up to the Time Point of Next Dosing (AUCtau,ss) for Pharmacokinetic (PK) Population (All Subjects)	AUC0-24,ss = area under the plasma concentration-time curve between 0 and 24 hours at steady state. AUCtau,ss = area under the plasma concentration-time curve over a dosing interval at steady state	27 days
Area Under the Concentration-time Curve of Pramipexole in Plasma at Steady State Over 24 Hours (AUC0-24,ss); in Case of ER up to the Time Point of Next Dosing (AUCtau,ss) for PK Population (Excluding Subjects Due to Emesis)	AUC0-24,ss = area under the plasma concentration-time curve between 0 and 24 hours at steady state. AUCtau,ss = area under the plasma concentration-time curve over a dosing interval at steady state	27 days
Maximum Steady State Concentration (Cmax,ss) for PK Population (All Subjects)	Cmax = maximum observed concentration of the analyte in plasma at steady state	27 days
Maximum Steady State Concentration (Cmax,ss) for PK Population (Excluding Subjects Due to Emesis)	Cmax,ss = maximum observed concentration of the analyte in plasma at steady state	27 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Dosing to the Maximum Measured Concentration of the Analyte in Plasma (Tmax) for PK Population (All Subjects)	tmax = time of maximum observed plasma concentration	27 days
Time From Dosing to the Maximum Measured Concentration of the Analyte in Plasma (Tmax) for PK Population (Excluding Subjects Due to Emesis)	tmax = time of maximum observed plasma concentration	27 days
Peak-to-trough Fluctuation (PTF) for PK Population (All Subjects)	PTF = Peak-to-trough fluctuation is measured as a percent	27 days
Peak-to-trough Fluctuation (PTF) for PK Population (Excluding Subjects Due to Emesis)	PTF = Peak-to-trough fluctuation is measured as a percent	27 days
Predose Steady State Concentration of the Analyte Immediately Before Administration of the Next Drug Administration (Cpre,ss) for PK Population (All Subjects)	Cpre,ss = pre-dose concentration of the analyte in plasma at steady state immediately before administration of the next dose	27 days
Predose Steady State Concentration of the Analyte Immediately Before Administration of the Next Drug Administration (Cpre,ss) for PK Population (Excluding Subjects Due to Emesis)	Cpre,ss = pre-dose concentration of the analyte in plasma at steady state immediately before administration of the next dose	27 days
Average Concentration in Plasma Under Steady-state Conditions (Cavg) for PK Population (All Subjects)	Cavg = Average concentration of the analyte in plasma at steady state	27 days
Average Concentration in Plasma Under Steady-state Conditions (Cavg) for PK Population (Excluding Subjects Due to Emesis)	Cavg = Average concentration of the analyte in plasma at steady state	27 days
Terminal Half-life of the Analyte in Plasma at Steady State (t1/2,ss) for PK Population (All Subjects)	t1/2,ss - Apparent plasma terminal elimination half-life at steady state	27 days
Terminal Half-life of the Analyte in Plasma at Steady State (t1/2,ss) for PK Population (Excluding Subjects Due to Emesis)	t1/2,ss - Apparent plasma terminal elimination half-life at steady state	27 days
Minimum Steady State Concentration (Cmin,ss) for PK Population (All Subjects)	Cmin,ss = Minimum observed concentration of the analyte in plasma at steady state	27 days
Minimum Steady State Concentration (Cmin,ss) for PK Population (Excluding Subjects Due to Emesis)	Cmin,ss = Minimum observed concentration of the analyte in plasma at steady state	27 days
The Apparent Clearance of the Analyte in Plasma at Steady State Following Oral Administration (CL/F,ss) for PK Population (All Subjects)	CL/F,ss = Apparent clearance of the analyte in the plasma at steady state following oral administration	27 days
The Apparent Clearance of the Analyte in Plasma at Steady State Following Oral Administration (CL/F,ss) for PK Population (Excluding Subjects Due to Emesis)	CL/F,ss = Apparent clearance of the analyte in the plasma at steady state following oral administration	27 days
Apparent Volume of Distribution During the Terminal Phase at Steady State Following Oral Administration (Vz/F,ss) for PK Population (All Subjects)	Vz/F,ss = Apparent volume of distribution during the terminal phase λz at steady state following oral administration	27 days
Apparent Volume of Distribution During the Terminal Phase at Steady State Following Oral Administration (Vz/F,ss) for PK Population (Excluding Subjects Due to Emesis)	Vz/F,ss = Apparent volume of distribution during the terminal phase λz at steady state following oral administration	27 days

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: October 1, 2010
• First Submitted That Met QC Criteria: October 1, 2010
• First Posted (Estimate): October 4, 2010

Study Record Updates

• Last Update Posted (Estimate): June 27, 2014
• Last Update Submitted That Met QC Criteria: June 17, 2014
• Last Verified: March 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: 248.665