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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00479401
First received: May 25, 2007
Last updated: June 20, 2014
Last verified: June 2014
  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
Early Parkinson Disease (Early PD)
Drug: Pramipexol Extended Release
Drug: Pramipexol Immediate Release
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
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 Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Total Score [ Time Frame: baseline and after 33 weeks treatment ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Patient rated evaluation of the PD symptoms 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    UPDRS II evaluates activities of daily living in a score 0-52. Decrease of the score means improvement

  • UPDRS Part III Total Score [ Time Frame: after 33 weeks treatment ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The Beck's Depression Inventory (BDI) is a 21-item self-rating scale that was originally designed as an instrument to assess the intensity of depressive symptoms (sadness, pessimism, sense of failure, dissatisfaction, guilt, expectation of punishment, dislike of self, self-accusation, suicidal ideation, episodes of crying, irritability, social withdrawal, indecisiveness, changes in body image, retardation, insomnia, fatigability, loss of appetite and weight, somatic preoccupation, low level of energy). Each item is scored from 0 (absent) to 3 (severe). The patients select the score which best describes their status in the last 7 days. Since its introduction in 1961, its use has been extended (also to PD patients) and today it is used also as a screening instrument as well as an outcome measure in depression treatment trials. The total score sums the 21 individual items yielding a score that can range from zero (minimal depression) to 63 (severe depression).

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

  • Parkinson's Disease Sleep Scale (PDSS) [ Time Frame: after 33 weeks treatment ] [ Designated as safety issue: Yes ]
    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)

  • Change From Baseline in Parkinson's Disease Quality of Life Questionnaire Total Score [ Time Frame: after 33 weeks treatment ] [ Designated as safety issue: No ]

    The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health which patients consider to be adversely affected by the disease. Higher scores are consistently associated with more severe symptoms of the disease such as tremor and stiffness, while lower scores indicate a better perceived health status. The 8 domains include:

    • mobility (e.g. fear of falling when walking): 10 items
    • activities of daily living (e.g. difficulty cutting food): 6 items
    • emotional well-being (e.g. feelings of isolation): 6 items
    • stigma (e.g. social embarrassment): 4 items
    • social support: 3 items
    • cognition: 4 items
    • communication: 3 items
    • bodily discomfort: 3 items.

    A total score is calculated by summing the responses to the 39 individual items and the total ranges from 0 (no problem at all) to 156 (maximum level of problem). A negative change in the total score indicates improvement.


  • Change From Baseline in European Quality of Life Visual Analog Scale [ Time Frame: after 33 weeks treatment ] [ Designated as safety issue: No ]
    European Quality of Life Visual Analog Scale (EQ-5D VAS) is a 20 centimeter vertical analog scale assessing the patient's general health status with scores ranging from 0 (worst imaginable health) to 100 (perfect health). A positive change in the scale indicates improvement in health status.

  • Patients Who Started to Use L-Dopa Rescue Medication [ Time Frame: from trial start on to any time before final assessment of the patient, up to 33 weeks ] [ Designated as safety issue: No ]
    L-dopa could be introduced as rescue medication based upon the clinical judgement of the investigator. descriptive on the Full Analysis Set (FAS) population

  • Number of Patients With Treatment Emergent Abnormal Behaviour as Indicated by the Modified Minnesota Impulsive Disorders Interview (mMIDI Questionnaire) [ Time Frame: from trial start on to any time before final assessment of the patient, up to 33 weeks ] [ Designated as safety issue: Yes ]
    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).

  • Possible Clinically Significant Abnormal Laboratory Parameters [ Time Frame: baseline and after 33 weeks of treatment ] [ Designated as safety issue: Yes ]
    The significant abnormality of values was based on standard criteria defined in appendix 16.1.10, LISTING 4 Criteria for clinically significant abnormalities based on normalized laboratory values.

  • Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events [ Time Frame: baseline and after 33 weeks of treatment ] [ Designated as safety issue: Yes ]

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 enrollment (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
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: 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
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: June 20, 2014
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
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 October 02, 2014