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

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01214109
First received: October 1, 2010
Last updated: June 17, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: pramipexole extended release
Drug: pramipexole immediate release
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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) [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    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

  • 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) [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    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

  • Maximum Steady State Concentration (Cmax,ss) for PK Population (All Subjects) [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    Cmax = maximum observed concentration of the analyte in plasma at steady state

  • Maximum Steady State Concentration (Cmax,ss) for PK Population (Excluding Subjects Due to Emesis) [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    Cmax,ss = maximum observed concentration of the analyte in plasma at steady state


Secondary Outcome Measures:
  • Time From Dosing to the Maximum Measured Concentration of the Analyte in Plasma (Tmax) for PK Population (All Subjects) [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    tmax = time of maximum observed plasma concentration

  • Time From Dosing to the Maximum Measured Concentration of the Analyte in Plasma (Tmax) for PK Population (Excluding Subjects Due to Emesis) [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    tmax = time of maximum observed plasma concentration

  • Peak-to-trough Fluctuation (PTF) for PK Population (All Subjects) [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    PTF = Peak-to-trough fluctuation is measured as a percent

  • Peak-to-trough Fluctuation (PTF) for PK Population (Excluding Subjects Due to Emesis) [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    PTF = Peak-to-trough fluctuation is measured as a percent

  • Predose Steady State Concentration of the Analyte Immediately Before Administration of the Next Drug Administration (Cpre,ss) for PK Population (All Subjects) [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    Cpre,ss = pre-dose concentration of the analyte in plasma at steady state immediately before administration of the next dose

  • 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) [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    Cpre,ss = pre-dose concentration of the analyte in plasma at steady state immediately before administration of the next dose

  • Average Concentration in Plasma Under Steady-state Conditions (Cavg) for PK Population (All Subjects) [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    Cavg = Average concentration of the analyte in plasma at steady state

  • Average Concentration in Plasma Under Steady-state Conditions (Cavg) for PK Population (Excluding Subjects Due to Emesis) [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    Cavg = Average concentration of the analyte in plasma at steady state

  • Terminal Half-life of the Analyte in Plasma at Steady State (t1/2,ss) for PK Population (All Subjects) [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    t1/2,ss - Apparent plasma terminal elimination half-life at steady state

  • Terminal Half-life of the Analyte in Plasma at Steady State (t1/2,ss) for PK Population (Excluding Subjects Due to Emesis) [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    t1/2,ss - Apparent plasma terminal elimination half-life at steady state

  • Minimum Steady State Concentration (Cmin,ss) for PK Population (All Subjects) [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    Cmin,ss = Minimum observed concentration of the analyte in plasma at steady state

  • Minimum Steady State Concentration (Cmin,ss) for PK Population (Excluding Subjects Due to Emesis) [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    Cmin,ss = Minimum observed concentration of the analyte in plasma at steady state

  • The Apparent Clearance of the Analyte in Plasma at Steady State Following Oral Administration (CL/F,ss) for PK Population (All Subjects) [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    CL/F,ss = Apparent clearance of the analyte in the plasma at steady state following oral administration

  • 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) [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    CL/F,ss = Apparent clearance of the analyte in the plasma at steady state following oral administration

  • Apparent Volume of Distribution During the Terminal Phase at Steady State Following Oral Administration (Vz/F,ss) for PK Population (All Subjects) [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    Vz/F,ss = Apparent volume of distribution during the terminal phase λz at steady state following oral administration

  • 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) [ Time Frame: 27 days ] [ Designated as safety issue: No ]
    Vz/F,ss = Apparent volume of distribution during the terminal phase λz at steady state following oral administration


Enrollment: 24
Study Start Date: December 2010
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01214109

Locations
China
248.665.86002 Boehringer Ingelheim Investigational Site
Beijing, China
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01214109     History of Changes
Other Study ID Numbers: 248.665
Study First Received: October 1, 2010
Results First Received: January 25, 2012
Last Updated: June 17, 2014
Health Authority: China: Food and Drug Administration

Additional relevant MeSH terms:
Pramipexole
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on September 16, 2014