Efficacy, Safety, Tolerability of Pramipexol ER Versus Pramipexol IR Versus Placebo in Early PD Patients

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00479401
First received: May 25, 2007
Last updated: May 18, 2012
Last verified: May 2012
  Purpose

The objectives of this trial conducted in early Parkinson's Disease (PD) patients are to determine the efficacy (as measured by the change from baseline to the end of the maintenance phase in the total score for the Unified Parkinson's Disease Rating Scale (UPDRS) Parts II and III combined), safety, and tolerability of Pramipexole Extended Release (ER) (in daily doses from 0.375mg to 4.5mg q.d.) in comparison to placebo, and to test for non-inferiority between the two formulations (ER and IR) of pramipexole.

In addition, the efficacy of Pramipexole Immediate Release (IR) will be compared to placebo, for assay sensitivity


Condition Intervention Phase
Parkinson Disease
Drug: Pramipexol Extended Release
Drug: Pramipexol Immediate Release
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: A Double-blind, Double-dummy, Placebo-controlled, Randomized, Three Parallel Groups Study Comparing the Efficacy, Safety and Tolerability of Pramipexole ER Versus Placebo and Versus Pramipexole IR Administered Orally Over a 26-week Maintenance Phase in Patients With Early Parkinsons Disease (PD).

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Change From Baseline in UPDRS (Unified Parkinson's Disease Rating Scale) Parts II+III Total Score [ Time Frame: baseline and after 33 weeks treatment ]
    Activities of daily living are scored from 0-52 in UPDRS II, result of motor examination scored 0-108 in UPDRS III. A decrease in the score means improvement.


Secondary Outcome Measures:
  • Percentage of Responders on the Clinical Global Impressions of Improvement (CGI-I) Scale [ Time Frame: after 18 weeks of treatment compared to baseline ]
    Clinicians evaluation in a rating scale of 7 steps, 1 meaning very much improved to 7 meaning very much worse. Responders are the patients with 'much improved' and 'very much improved' on the scale

  • Percentage of Responders on the Patients Global Impressions of Improvement (PGI-I) Scale [ Time Frame: after 18 weeks of treatment compared to baseline ]
    Patient rated evaluation of the PD sympoms on a rating scale of 7 steps, 1 meaning very much better to 7 meaning very much worse. Responders are the patients with 'much better' and 'very much better' on the score.

  • UPDRS II+III Responder Rate (at Least 20% Improvement) [ Time Frame: after 33 weeks treatment ]
    Responders are defined as at least 20% decrease in the UPDRS II+III score. UPDRS II+III ranges 0-160 scores from best to worse.

  • UPDRS Part I Change From Baseline [ Time Frame: baseline and after 33 weeks treatment ]
    UPDRS I evaluates mentation behaviour and mood with a total score of 0-16. Decrease in the scores means improvement

  • UPDRS Part II Total Score [ Time Frame: after 33 weeks treatment ]
    UPDRS II evaluates activities of dailiy living in a score 0-52. Decrease of the score means improvement

  • UPDRS Part III Total Score [ Time Frame: after 33 weeks treatment ]
    UPDRS III is the result of a motor examination with the scores 0-108. A decrease in the scores means improvement

  • Beck's Depression Inventory Version I A [ Time Frame: after 33 weeks treatment ]
    21 item self-rating scale to assess depressive symptoms. Each item is scored from absent (0) to severe (3.) A decrease in the score means improvement

  • Likert Scale for Pain Related to PD [ Time Frame: after 33 weeks treatment ]
    Patient assessed 11 units on a scale from 'no pain' to 'unbearable pain'. Decrease of the score means improvement

  • Parkinson's Disease Sleep Scale [ Time Frame: after 33 weeks treatment ]
    PDSS is a self-rated instrument addressing 15 commonly reported symptoms associated with sleep disturbance on 15 visual analogue scales (VAS: 0 to 10 cm) each ranging from worst score ('awful or always' at the left extremity to the best score ('excellent or never' at the right extremity) An increase in the score means improvement. Worst possible score 0, best score 150)

  • Parkinson's Disease Quality of Life Questionnaire [ Time Frame: after 33 weeks treatment ]
    Self administered questionnaire addressing 8 domains of health affected by PD. Lower scores relate to better preserved health status

  • European Quality of Life Scale [ Time Frame: after 33 weeks treatment ]
    Standardized health-related quality of life questionnaire. An increase of the score means improvement

  • Patients Who Started to Use L-Dopa Rescue Medication [ Time Frame: from trial start on to any time before final assessment of the patient ]
    L-dopa could be introduced as rescue medication based upon the clinical judgement of the investigator. descriptive on the FAS population

  • Number of Patients With Treatment Emergent Abnormal Behaviour as Indicated by the Modified Minnesota Impulsive Disorders Interview (mMIDI Questionnaire) [ Time Frame: any time during the study ]
    mMIDI is a semi-structured clinical interview to assess pathological gambling (12 questions, positive screen if patient answers 'yes' to question 1 and to at least 5 of the rest of the questions), compulsive buying (9 questions from 1a to 4c, positive screen if the patient answers 'yes' to 1a, 2a, 3a, and 4a) and compulsive sexual behaviour (4 questions, positive screen if patient answers 'yes' to question 1,2,3, or 4).


Enrollment: 539
Study Start Date: May 2007
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pramipexole Extended Release (PPX ER) Drug: Pramipexol Extended Release
Experimental: Pramipexole Immediate Release (PPX IR) Drug: Pramipexol Immediate Release
Placebo Comparator: Placebo Drug: Placebo

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patient with idiopathic Parkinsons disease (PD) confirmed by at least two of the following signs: resting tremor, bradykinesia, rigidity.
  2. Parkinsons disease diagnosed within 5 years.
  3. Patients 30 years of age or older at the time of diagnosis.
  4. Modified Hoehn and Yahr stage of 1 to 3.
  5. Patients requiring additional therapy/ introduction of therapy (for de novo patients) to treat their parkinsonian symptoms at the time of enrolment (screening visit, V1) according to the investigators judgement.

Exclusion Criteria:

  1. Atypical parkinsonian syndromes due to drugs (e.g., metoclopramide, flunarizine), metabolic disorders (e.g., Wilson's disease), encephalitis or degenerative diseases (e.g., progressive supranuclear palsy).
  2. Dementia, as defined by a Mini-Mental State Exam score < 24 at screening visit
  3. Any psychiatric disorder according to Diagnostic and Statistical Manual of Mental Disorders 4th (DSM-IV)
  4. History of psychosis
  5. Clinically significant electrocardiogram (ECG) abnormalities at screening visit
  6. Clinically significant hypotension
  7. Malignant melanoma or history of previously treated malignant melanoma
  8. Any other clinically significant disease, whether treated or not, that could put the patient at risk or could prevent compliance or completion of the study
  9. Pregnancy
  10. Sexually active female of childbearing potential not using a medically approved method of birth control
  11. Serum levels of Aspartate Aminotransferase (AST) , Alanine Aminotransferase (ALT), alkaline phosphatases or bilirubin > 2 Upper Limit of Normal (ULN)
  12. Patients with a creatinine clearance < 50 mL/min
  13. Any dopamine agonist (including pramipexole) within 4 weeks prior to baseline visit, or L-Dopa within 8 weeks prior to baseline visit.
  14. Total cumulative duration of prior exposure to Levodopa of more than 3 months.
  15. Any medication (including intra-muscular formulations) with central dopaminergic antagonist activity within 4 weeks prior to the baseline visit
  16. Any of the following drugs within 4 weeks prior to the baseline visit: methylphenidate, cinnarizine, amphetamines.
  17. Flunarizine within 3 months prior to baseline visit
  18. Known hypersensitivity to Pramipexole or its excipients
  19. Drug abuse (including alcohol), according to Investigators judgement, within 2 years prior to screening.
  20. Participation in other investigational drug studies or use of other investigational drugs within one month or five times the half-life of the investigational drug
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00479401

  Show 95 Study Locations
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: NCT00479401     History of Changes
Other Study ID Numbers: 248.524, Eudract No 2007-000073-39
Study First Received: May 25, 2007
Results First Received: November 20, 2009
Last Updated: May 18, 2012
Health Authority: Argentina: A.N.M.A.T. (Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica)
Austria: Federal Office for Safety in Health Care
Czech Republic: SUKL (state institute for drug control)
Finland: Finnish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy, H-1051 Budapest
India: Drug Control General of India
Japan: Ministry of Health, Labor and Welfare
Malaysia: Ministry of Health, Malaysia
Russia: Ministry of Healthcare and Social Development of Russian Federation, Moscow
Slovakia: SUKL (state institute for drug control)
Taiwan: Department of Health, Executive Yuan, Taiwan
Ukraine: Ministry of Health Care of Ukraine (MoH of Ukraine)
United States: Food and Drug Administration

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Pramipexol
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 April 14, 2014