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

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.

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

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.

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 I evaluates mentation behaviour and mood with a total score of 0-16. Decrease in the scores means improvement

UPDRS II evaluates activities of daily living in a score 0-52. Decrease of the score means improvement

UPDRS III is the result of a motor examination with the scores 0-108. A decrease in the scores means improvement

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).

Patient assessed 11 units on a scale from 'no pain' to 'unbearable pain'. Decrease of the score means improvement

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)

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.

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.

L-dopa could be introduced as rescue medication based upon the clinical judgement of the investigator. descriptive on the Full Analysis Set (FAS) population

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).

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.