A 12-week Study of Pramipexole Extended Release (ER) in Patients With Parkinson's Disease (PD), Followed by a 52-week Long-term Treatment Period

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00560508
First received: November 16, 2007
Last updated: July 29, 2014
Last verified: July 2014
  Purpose

The objective of this trial is to investigate the safety, tolerability, trough plasma concentration, and efficacy of pramipexole ER in comparison with those of pramipexole IR administrated orally for 12 weeks in patients with PD on levodopa (L-DOPA) therapy (the double-blind period). The double-blind period will be followed by the open-label 52 week administration of pramipexole ER to evaluate the long term safety and efficacy (the open-label period).


Condition Intervention Phase
Parkinson Disease
Drug: Pramipexole Immediate Release
Drug: Pramipexole Extended Release
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Double-dummy, Randomised, Parallel-group Study to Investigate the Safety, Tolerability, Trough Plasma Concentration, and Efficacy of Pramipexole ER Versus Pramipexole Immediate Release (IR) Administered Orally for 12 Weeks in Patients With Parkinson's Disease (PD) on L-dopa Therapy, Followed by a 52-week Open-label Long-term Treatment Period to Evaluate the Long-term Safety and Efficacy of Pramipexole ER

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Percentage of Participants Who Experienced Adverse Events [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    An adverse event is defined as any untoward medical occurrence


Secondary Outcome Measures:
  • Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Total Score [ Time Frame: baseline and after 12 weeks treatment ] [ Designated as safety issue: No ]
    UPDRS II+III ranging from 0 point(normal) to 160 point (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms

  • Change From Baseline in Percentage Off-time [ Time Frame: baseline and after 12 weeks treatment ] [ Designated as safety issue: No ]
    Percentage off-time during waking hours in the last two days based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). Off-time describes a period when the patient experiences increased parkinsonian symptoms (e.g. immobility or inability to move with ease).

  • Change From Baseline in Percentage On-time Without Dyskinesia [ Time Frame: baseline and after 12 weeks treatment ] [ Designated as safety issue: No ]
    Percentage on-time without dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.

  • Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia [ Time Frame: baseline and after 12 weeks treatment ] [ Designated as safety issue: No ]
    Percentage on-time with non-troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0(worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.

  • Change From Baseline in Percentage On-time Without Dyskinesia or With Non-troublesome Dyskinesia [ Time Frame: baseline and after 12 weeks treatment ] [ Designated as safety issue: No ]
    Percentage on-time without dyskinesia or non-troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.

  • Change From Baseline in Percentage On-time With Troublesome Dyskinesia [ Time Frame: baseline and after 12 weeks treatment ] [ Designated as safety issue: No ]
    Percentage on-time with troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.

  • Responder Rate For Clinical Global Impression of Improvement (CGI-I) [ Time Frame: baseline and after 12 weeks treatment ] [ Designated as safety issue: No ]
    CGI-I scores ranging from '1' (very much improved) to '7' (very much worse), CGI-I responder have scoring of 1 or 2 (at least much improved)

  • Responder Rate For Patient Global Impression of Improvement (PGI-I) [ Time Frame: baseline and after 12 weeks treatment ] [ Designated as safety issue: No ]
    PGI-I scores ranging from '1' (very much better) to '7' (very much worse), PGI-I responder have scoring of 1 or 2 (at least much better)

  • Change From Baseline in UPDRS Part I Score [ Time Frame: baseline and after 12 weeks treatment ] [ Designated as safety issue: No ]
    UPDRS Part I ranging from 0 (normal) to 16 (severe). UPDRS Part I measures Mentation, Behavior and Mood

  • Change From Baseline in UPDRS Part II Score [ Time Frame: baseline and after 12 weeks treatment ] [ Designated as safety issue: No ]
    UPDRS Part II ranging from 0 (normal) to 52 (severe). UPDRS Part II is calculated as the average of UPDRS Part II at on and UPDRS Part II at off-period for each of the 13 activities.

  • Change From Baseline in UPDRS Part III Score [ Time Frame: baseline and after 12 weeks treatment ] [ Designated as safety issue: No ]
    UPDRS Part III ranging from 0 (normal) to 108 (severe). UPDRS Part III measures motor symptoms

  • Change From Baseline in UPDRS Part IV Score [ Time Frame: baseline and after 12 weeks treatment ] [ Designated as safety issue: No ]
    UPDRS Part IV ranging from 0 (normal) to 23 (severe). UPDRS Part IV measures complications of therapy

  • UPDRS Parts II+III Total Score Responder Rate (at Least 20% Improvement) [ Time Frame: baseline and after 12 weeks treatment ] [ Designated as safety issue: No ]
    Responders are defined as at least 20% decrease in the UPDRS Parts II+III Total Score ranges 0-160 scores from best to worse

  • Change From Baseline in L-dopa Daily Dose [ Time Frame: baseline and after 12 weeks treatment ] [ Designated as safety issue: No ]
    The L-dopa daily dose was recorded in the electronic case report form (eCRF) at each trial visit.

  • Trough Plasma Concentration at Steady State [ Time Frame: at Visit 8 after pramipexole ER 4.5mg and IR 4.5mg treatment ] [ Designated as safety issue: No ]
    Geometric mean (gMean) was calculated for trough plasma concentrations of pramipexole at steady state after administration of pramipexole IR 4.5mg and pramipexole ER 4.5mg.

  • Dose Proportionality of Trough Plasma Concentration at Steady State After Pramipexole ER Treatment [ Time Frame: from Visit 1 to Visit 8 after pramipexole ER ] [ Designated as safety issue: No ]
    Dose proportionality of trough plasma concentrations at steady state is explored by using the power model that described the functional relationship between the dose and plasma concentration

  • Change From End of Double-Blind Period in UPDRS (Unified Parkinson's Disease Rating Scale) Parts II+III Total Score (Open-label: Dose Adjustment Phase) [ Time Frame: Week 12 to Week 16 ] [ Designated as safety issue: No ]
    UPDRS II+III ranging from 0 point(normal) to 160 point (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms. Least square means and standard errors presented are from ANCOVA with factors treatment and covariate baseline.

  • Percentage of Patients With no Worsening of UPDRS Parts II+III Total Score by More Than 15% From Week 12 to Week 16 (Open-label: Dose Adjustment Phase) [ Time Frame: Week 12 to Week 16 ] [ Designated as safety issue: No ]
    Percentage of patients with no worsening of UPDRS Parts II+III Total Score by more than 15% from week 12 to week 16 (Open-label: Dose Adjustment Phase)

  • Clinical Global Impression of Improvement (CGI-I) at Week 16 Compared to Patient's CGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) [ Time Frame: Week 12 to Week 16 ] [ Designated as safety issue: No ]
    Clinical Global Impression of Improvement (CGI-I) at week 16 compared to patient's CGI-I status at week 12. CGI-I scores ranging from '1' (very much improved) to '7' (very much worse)

  • Patient Global Impression of Improvement (PGI-I) at Week 16 Compared to Patient's PGI-I Status at Week 12 (Open-label: Dose Adjustment Phase) [ Time Frame: Week 12 to Week 16 ] [ Designated as safety issue: No ]
    Patient Global Impression of Improvement (PGI-I) at week 16 compared to patient's PGI-I status at week 12. PGI-I scores ranging from '1' (very much better) to '7' (very much worse).

  • Change From Baseline in UPDRS (Unified Parkinson's Disease Rating Scale) Parts II+III Total Score (Open-label: Maintenance Phase) [ Time Frame: Baseline and after 64 weeks treatment ] [ Designated as safety issue: No ]
    UPDRS II+III ranging from 0 point(normal) to 160 point (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms

  • UPDRS Parts II+III Total Score Responder Rate (at Least 20% Improvement) (Open-label: Maintenance Phase) [ Time Frame: baseline and after 64 weeks treatment ] [ Designated as safety issue: No ]
    Responders are defined as at least 20% decrease in the UPDRS Parts II+III Total Score ranges 0-160 scores from best to worse

  • Change From Baseline in Percentage Off-time (Open-label: Maintenance Phase) [ Time Frame: baseline and after 64 weeks treatment ] [ Designated as safety issue: No ]
    Percentage off-time during waking hours in the last two days based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). Off-time describes a period when the patient experiences increased parkinsonian symptoms (e.g. immobility or inability to move with ease).

  • Change From Baseline in Percentage On-time Without Dyskinesia (Open-label: Maintenance Phase) [ Time Frame: baseline and after 64 weeks treatment ] [ Designated as safety issue: No ]
    Percentage on-time without dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.

  • Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia (Open-label Maintenance Phase) [ Time Frame: baseline and after 64 weeks treatment ] [ Designated as safety issue: No ]
    Percentage on-time with non-troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0(worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.

  • Change From Baseline in Percentage On-time Without Dyskinesia or With Non-troublesome Dyskinesia (Open-label Maintenance Phase) [ Time Frame: baseline and after 64 weeks treatment ] [ Designated as safety issue: No ]
    Percentage on-time without dyskinesia or non-troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.

  • Change From Baseline in Percentage On-time With Troublesome Dyskinesia (Open-label Maintenance Phase) [ Time Frame: baseline and after 64 weeks treatment ] [ Designated as safety issue: No ]
    Percentage on-time with troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.

  • Change From Baseline in L-dopa Daily Dose (Open-label Maintenance Phase) [ Time Frame: baseline and after 64 weeks treatment ] [ Designated as safety issue: No ]
    The L-dopa daily dose was recorded in the electronic case report form (eCRF) at each trial visit.

  • Change From Baseline in UPDRS Part I Score (Open-label: Maintenance Phase) [ Time Frame: baseline and after 64 weeks treatment ] [ Designated as safety issue: No ]
    UPDRS Part I ranging from 0 (normal) to 16 (severe). UPDRS Part I measures Mentation, Behavior and Mood

  • Change From Baseline in UPDRS Part II Score (Open-label: Maintenance Phase) [ Time Frame: baseline and after 64 weeks treatment ] [ Designated as safety issue: No ]
    UPDRS Part II ranging from 0 (normal) to 52 (severe). UPDRS Part II is calculated as the average of UPDRS Part II at on and UPDRS Part II at off-period for each of the 13 activities.

  • Change From Baseline in UPDRS Part III Score (Open-label: Maintenance Phase) [ Time Frame: baseline and after 64 weeks treatment ] [ Designated as safety issue: No ]
    UPDRS Part III ranging from 0 (normal) to 108 (severe). UPDRS Part III measures motor symptoms

  • Change From Baseline in UPDRS Part IV Score (Open-label: Maintenance Phase) [ Time Frame: baseline and after 64 weeks treatment ] [ Designated as safety issue: No ]
    UPDRS Part IV ranging from 0 (normal) to 23 (severe). UPDRS Part IV measures complications of therapy


Enrollment: 112
Study Start Date: November 2007
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pramipexole Extended Release
patient to receive a tablet containing 0.375 mg Pramipexole ER once a day plus containing 0.125 mg Pramipexole IR placebo twice a day -> a tablet containing 1.5 mg Pramipexole ER three times daily (TID) plus 0.5 mg Pramipexole IR placebo TID
Drug: Pramipexole Extended Release
titration as individually needed (0.375 mg -4.5 mg daily)
Active Comparator: Pramipexole Immediate Release
patient to receive a tablet containing 0.125 mg Pramipexole IR twice a day plus containing 0.375 mg Pramipexole ER placebo once a day -> a tablet containing 0.5 mg Pramipexole IR three times daily (TID) plus 1.5 mg Pramipexole ER placebo TID
Drug: Pramipexole Immediate Release
titrated as individually needed (0.25 mg - 4.5 mg daily)

  Eligibility

Ages Eligible for Study:   1 Year and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  1. Male or female patients with diagnosis of PD including juvenile Parkinsonism, in whom the onset began at the age of forty or younger.
  2. Patients with a modified Hoehn and Yahr scale of II to IV at "on" time.
  3. Patients who have received an individual dosage of L-DOPA (either standard L-DOPA or L-DOPA with dopa-decarboxylase inhibitor) at a stable dose for at least 4 weeks before the baseline visit (Visit 2).
  4. Patients who exhibit any therapeutically problematic issues or status based on L-DOPA therapy:

    • wearing-off phenomena
    • no on /delayed on
    • dystonia at off time
    • on-off phenomena
    • freezing phenomena at off time
    • the sub-optimal dose of L-DOPA had been administered due to side effects (such as dyskinesia), or therapeutical strategy

Exclusion criteria

  1. Atypical parkinsonian syndromes due to drugs, metabolic disorders, encephalitis or degenerative diseases.
  2. Dementia, as defined by a Mini-Mental State Examination (MMSE) score <24 at screening visit.
  3. Any psychiatric disorder according to DSM-IV criteria that could prevent compliance or completion of the trial and/or put the patient at risk if he/she takes part in the trial.
  4. History of psychosis, except history of drug induced hallucinations (provided the investigator considers that participation in the trial would not represent a significant risk for the patient).
  5. Clinically significant ECG abnormalities at screening visit, according to investigator's judgement.
  6. Clinically significant hypotension or symptomatic orthostatic hypotension (i.e., clinical symptoms of orthostatic hypotension such as dizziness postural etc associated with a decline >=20 mmHg in systolic blood pressure and a decline >=10 mmHg in diastolic blood pressure, at one minute after standing compared with the previous supine systolic and diastolic blood pressure obtained after 5 minutes of quiet rest) either at screening visit or at baseline visit.
  7. Any other clinically significant disease, whether treated or not, that could put the patient at risk or could prevent compliance or completion of the trial.
  8. Pregnancy (to be excluded by serum pregnancy test at screening visit) or breast-feeding.
  9. Sexually active female of childbearing potential not using a medically approved method of birth control within one month before to the screening visit and throughout the trial period.
  10. Serum levels of AST, ALT, alkaline phosphatases or bilirubin >2 upper limits of normal .
  11. Patients with a creatinine clearance <50 mL/min
  12. Patients with a complication or signs of malignant tumours or those within 5 years after the treatment.
  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: NCT00560508

Locations
Japan
248.610.019 Boehringer Ingelheim Investigational Site
Akashi, Hyogo, Japan
248.610.020 Boehringer Ingelheim Investigational Site
Akita, Akita, Japan
248.610.006 Boehringer Ingelheim Investigational Site
Aomori, Aomori, Japan
248.610.017 Boehringer Ingelheim Investigational Site
Asahikawa, Hokkaido, Japan
248.610.018 Boehringer Ingelheim Investigational Site
Asahikawa, Hokkaido, Japan
248.610.001 Boehringer Ingelheim Investigational Site
Bunkyo-ku, Tokyo, Japan
248.610.014 Boehringer Ingelheim Investigational Site
Fuchu, Tokyo, Japan
248.610.011 Boehringer Ingelheim Investigational Site
Fukuoka, Fukuoka, Japan
248.610.015 Boehringer Ingelheim Investigational Site
Iwamizawa,Hokkaido, Japan
248.610.003 Boehringer Ingelheim Investigational Site
Kodaira, Tokyo, Japan
248.610.008 Boehringer Ingelheim Investigational Site
Kyoto, Kyoto, Japan
248.610.021 Boehringer Ingelheim Investigational Site
Kyoto, Kyoto, Japan
248.610.010 Boehringer Ingelheim Investigational Site
Morioka, Iwate, Japan
248.610.005 Boehringer Ingelheim Investigational Site
Okayama, Okayama, Japan
248.610.012 Boehringer Ingelheim Investigational Site
Osaka, Osaka, Japan
248.610.004 Boehringer Ingelheim Investigational Site
Sagamihara, Kanagawa, Japan
248.610.009 Boehringer Ingelheim Investigational Site
Shimogyo-ku, Kyoto, Kyoto, Japan
248.610.007 Boehringer Ingelheim Investigational Site
Shiroishi, Miyagi, Japan
248.610.002 Boehringer Ingelheim Investigational Site
Takamatsu, Kagawa, Japan
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00560508     History of Changes
Other Study ID Numbers: 248.610
Study First Received: November 16, 2007
Results First Received: November 25, 2010
Last Updated: July 29, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Parkinson Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Parkinsonian Disorders
Pramipexole
Anti-Dyskinesia Agents
Antioxidants
Antiparkinson Agents
Central Nervous System Agents
Dopamine Agents
Dopamine Agonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014