Efficacy, Safety, Tolerability of Pramipexol ER Versus Pramipexol IR Versus Placebo in Early PD Patients
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
|Early Parkinson Disease (Early PD)||Drug: Pramipexol Extended Release Drug: Pramipexol Immediate Release Drug: Placebo||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, 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).|
- Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) 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.
- 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 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 ]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 daily 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 ]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 ]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 ]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 ]
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 ]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 ]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 ]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 ]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 ]
|Study Start Date:||May 2007|
|Primary Completion Date:||November 2008 (Final data collection date for primary outcome measure)|
|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|
Please refer to this study by its ClinicalTrials.gov identifier: NCT00479401
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|Study Chair:||Boehringer Ingelheim||Boehringer Ingelheim|