Early Parkinson Disease (Early PD)
Conditions
Brief summary
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
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Total Score | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Responders on the Patients Global Impressions of Improvement (PGI-I) Scale | 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) | 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 | 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 | 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 | 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 | 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 | after 33 weeks treatment | Patient assessed 11 units on a scale from 'no pain' to 'unbearable pain'. Decrease of the score means improvement |
| Percentage of Responders on the Clinical Global Impressions of Improvement (CGI-I) Scale | 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 |
| Change From Baseline in Parkinson's Disease Quality of Life Questionnaire Total Score | 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 | 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 | 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) | 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 | 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 | baseline and after 33 weeks of treatment | — |
| Parkinson's Disease Sleep Scale (PDSS) | 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) |
Countries
Argentina, Austria, Czechia, Finland, Germany, Hungary, India, Japan, Malaysia, Russia, Slovakia, Taiwan, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pramipexole Extended Release (PPX ER) PPX ER tablets taken once in the morning | 223 |
| Pramipexole Immediate Release (PPX IR) PPX IR tablets taken three times a day | 213 |
| Placebo Placebo to PPX ER once and to PPX IR three times a day | 103 |
| Total | 539 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 24 | 20 | 4 |
| Overall Study | Exclusion criteria, relocation | 4 | 3 | 0 |
| Overall Study | Lack of Efficacy | 2 | 2 | 4 |
| Overall Study | Lost to Follow-up | 1 | 1 | 1 |
| Overall Study | Protocol Violation | 2 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 16 | 10 | 2 |
Baseline characteristics
| Characteristic | Pramipexole Extended Release (PPX ER) | Pramipexole Immediate Release (PPX IR) | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 61.3 years STANDARD_DEVIATION 9.8 | 61.7 years STANDARD_DEVIATION 9.6 | 62.0 years STANDARD_DEVIATION 9.6 | 61.6 years STANDARD_DEVIATION 9.7 |
| Sex: Female, Male Female | 96 Participants | 92 Participants | 52 Participants | 240 Participants |
| Sex: Female, Male Male | 127 Participants | 121 Participants | 51 Participants | 299 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 142 / 223 | 133 / 213 | 44 / 103 |
| serious Total, serious adverse events | 16 / 223 | 11 / 213 | 4 / 103 |
Outcome results
Primary
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Total Score
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.
Time frame: baseline and after 33 weeks treatment
Population: Full Analysis Set, all randomized patients, received at least one dose of study drug and provided any post baseline efficacy assessment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pramipexole Extended Release (PPX ER) | Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Total Score | -8.6 units on a scale |
| Pramipexole Immediate Release (PPX IR) | Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Total Score | -8.8 units on a scale |
| Placebo | Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Total Score | -3.8 units on a scale |
Comparison: A non-inferiority hypothesis (H0: μER - μIR \< -3 vs. H1: μER - μIR ≥ -3) comparing pramipexole ER to pramipexole IR was tested using a non-inferiority margin of -3 points.95% CI: [-2.2, 1.7]ANCOVA
Secondary
Beck's Depression Inventory Version I A
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).
Time frame: after 33 weeks treatment
Population: Full Analysis Set, all randomized patients, received at least one dose of study drug and provided any post baseline efficacy assessment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pramipexole Extended Release (PPX ER) | Beck's Depression Inventory Version I A | -2.0 units on a scale |
| Pramipexole Immediate Release (PPX IR) | Beck's Depression Inventory Version I A | -2.7 units on a scale |
| Placebo | Beck's Depression Inventory Version I A | -2.1 units on a scale |
Secondary
Change From Baseline in European Quality of Life Visual Analog Scale
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.
Time frame: after 33 weeks treatment
Population: Full Analysis Set, all randomized patients, received at least one dose of study drug and provided any post baseline efficacy assessment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pramipexole Extended Release (PPX ER) | Change From Baseline in European Quality of Life Visual Analog Scale | 4.0 units on a scale |
| Pramipexole Immediate Release (PPX IR) | Change From Baseline in European Quality of Life Visual Analog Scale | 6.6 units on a scale |
| Placebo | Change From Baseline in European Quality of Life Visual Analog Scale | 3.2 units on a scale |
Secondary
Change From Baseline in Parkinson's Disease Quality of Life Questionnaire Total Score
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.
Time frame: after 33 weeks treatment
Population: Full Analysis Set, all randomized patients, received at least one dose of study drug and provided any post baseline efficacy assessment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pramipexole Extended Release (PPX ER) | Change From Baseline in Parkinson's Disease Quality of Life Questionnaire Total Score | -4.1 units on a scale |
| Pramipexole Immediate Release (PPX IR) | Change From Baseline in Parkinson's Disease Quality of Life Questionnaire Total Score | -6.5 units on a scale |
| Placebo | Change From Baseline in Parkinson's Disease Quality of Life Questionnaire Total Score | -2.1 units on a scale |
Secondary
Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events
Time frame: baseline and after 33 weeks of treatment
Population: Treated set (TS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pramipexole Extended Release (PPX ER) | Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events | Hypertension | 6 participants |
| Pramipexole Extended Release (PPX ER) | Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events | Orthostatic hypotension | 7 participants |
| Pramipexole Extended Release (PPX ER) | Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events | Hypotension | 0 participants |
| Pramipexole Extended Release (PPX ER) | Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events | Weight increased | 0 participants |
| Pramipexole Extended Release (PPX ER) | Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events | Weight decreased | 2 participants |
| Pramipexole Extended Release (PPX ER) | Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events | Blood pressure diastolic increased | 0 participants |
| Pramipexole Immediate Release (PPX IR) | Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events | Blood pressure diastolic increased | 1 participants |
| Pramipexole Immediate Release (PPX IR) | Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events | Hypertension | 7 participants |
| Pramipexole Immediate Release (PPX IR) | Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events | Weight increased | 7 participants |
| Pramipexole Immediate Release (PPX IR) | Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events | Weight decreased | 3 participants |
| Pramipexole Immediate Release (PPX IR) | Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events | Orthostatic hypotension | 1 participants |
| Pramipexole Immediate Release (PPX IR) | Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events | Hypotension | 6 participants |
| Placebo | Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events | Orthostatic hypotension | 1 participants |
| Placebo | Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events | Hypotension | 1 participants |
| Placebo | Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events | Blood pressure diastolic increased | 0 participants |
| Placebo | Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events | Weight increased | 0 participants |
| Placebo | Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events | Hypertension | 5 participants |
| Placebo | Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events | Weight decreased | 0 participants |
Secondary
Likert Scale for Pain Related to PD
Patient assessed 11 units on a scale from 'no pain' to 'unbearable pain'. Decrease of the score means improvement
Time frame: after 33 weeks treatment
Population: Full Analysis Set, all randomized patients, received at least one dose of study drug and provided any post baseline efficacy assessment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pramipexole Extended Release (PPX ER) | Likert Scale for Pain Related to PD | -0.2 units on a scale |
| Pramipexole Immediate Release (PPX IR) | Likert Scale for Pain Related to PD | -0.1 units on a scale |
| Placebo | Likert Scale for Pain Related to PD | 0.2 units on a scale |
Secondary
Number of Patients With Treatment Emergent Abnormal Behaviour as Indicated by the Modified Minnesota Impulsive Disorders Interview (mMIDI Questionnaire)
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).
Time frame: from trial start on to any time before final assessment of the patient, up to 33 weeks
Population: Treated Set (TS), all randomized patients, who were dispensed study medication and documented to have taken at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pramipexole Extended Release (PPX ER) | Number of Patients With Treatment Emergent Abnormal Behaviour as Indicated by the Modified Minnesota Impulsive Disorders Interview (mMIDI Questionnaire) | 4 patients |
| Pramipexole Immediate Release (PPX IR) | Number of Patients With Treatment Emergent Abnormal Behaviour as Indicated by the Modified Minnesota Impulsive Disorders Interview (mMIDI Questionnaire) | 3 patients |
| Placebo | Number of Patients With Treatment Emergent Abnormal Behaviour as Indicated by the Modified Minnesota Impulsive Disorders Interview (mMIDI Questionnaire) | 1 patients |
Secondary
Parkinson's Disease Sleep Scale (PDSS)
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)
Time frame: after 33 weeks treatment
Population: Full Analysis Set, all randomized patients, received at least one dose of study drug and provided any post baseline efficacy assessment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pramipexole Extended Release (PPX ER) | Parkinson's Disease Sleep Scale (PDSS) | 2.3 units on a scale |
| Pramipexole Immediate Release (PPX IR) | Parkinson's Disease Sleep Scale (PDSS) | 5.6 units on a scale |
| Placebo | Parkinson's Disease Sleep Scale (PDSS) | 5.6 units on a scale |
Secondary
Patients Who Started to Use L-Dopa Rescue Medication
L-dopa could be introduced as rescue medication based upon the clinical judgement of the investigator. descriptive on the Full Analysis Set (FAS) population
Time frame: from trial start on to any time before final assessment of the patient, up to 33 weeks
Population: Full Analysis Set, all randomized patients, received at least one dose of study drug and provided any post baseline efficacy assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pramipexole Extended Release (PPX ER) | Patients Who Started to Use L-Dopa Rescue Medication | 15 patients |
| Pramipexole Immediate Release (PPX IR) | Patients Who Started to Use L-Dopa Rescue Medication | 9 patients |
| Placebo | Patients Who Started to Use L-Dopa Rescue Medication | 22 patients |
Secondary
Percentage of Responders on the Clinical Global Impressions of Improvement (CGI-I) Scale
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
Time frame: after 18 weeks of treatment compared to baseline
Population: Full Analysis Set 1, all randomized patients, received at least one dose of study drug and provided any post baseline efficacy assessment and completed 18 weeks of treatment or discontinued prematurely at the interim cut off date Apr 2008
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pramipexole Extended Release (PPX ER) | Percentage of Responders on the Clinical Global Impressions of Improvement (CGI-I) Scale | 37 Percentage of Participants |
| Pramipexole Immediate Release (PPX IR) | Percentage of Responders on the Clinical Global Impressions of Improvement (CGI-I) Scale | 48 Percentage of Participants |
| Placebo | Percentage of Responders on the Clinical Global Impressions of Improvement (CGI-I) Scale | 18 Percentage of Participants |
Secondary
Percentage of Responders on the Patients Global Impressions of Improvement (PGI-I) 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.
Time frame: after 18 weeks of treatment compared to baseline
Population: Full Analysis Set 1, all randomized patients, received at least one dose of study drug and provided any post baseline efficacy assessment and completed 18 weeks of treatment or discontinued prematurely at the interim cut off date Apr 2008
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pramipexole Extended Release (PPX ER) | Percentage of Responders on the Patients Global Impressions of Improvement (PGI-I) Scale | 35.6 Percentage of Participants |
| Pramipexole Immediate Release (PPX IR) | Percentage of Responders on the Patients Global Impressions of Improvement (PGI-I) Scale | 23.8 Percentage of Participants |
| Placebo | Percentage of Responders on the Patients Global Impressions of Improvement (PGI-I) Scale | 12 Percentage of Participants |
Secondary
Possible Clinically Significant Abnormal Laboratory Parameters
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.
Time frame: baseline and after 33 weeks of treatment
Population: Treated Set Labs (TSLabs), all patients in TS with a clinical laboratory measurements at baseline and at the last visit.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Pramipexole Extended Release (PPX ER) | Possible Clinically Significant Abnormal Laboratory Parameters | GGT - increase | 3 participants | — |
| Pramipexole Extended Release (PPX ER) | Possible Clinically Significant Abnormal Laboratory Parameters | Neut., poly (segs), absol. - decrease | 1 participants | — |
| Pramipexole Extended Release (PPX ER) | Possible Clinically Significant Abnormal Laboratory Parameters | Red blood cell ct. - decrease | 1 participants | — |
| Pramipexole Extended Release (PPX ER) | Possible Clinically Significant Abnormal Laboratory Parameters | Alkaline phosphatase - increase | 0 participants | — |
| Pramipexole Extended Release (PPX ER) | Possible Clinically Significant Abnormal Laboratory Parameters | Sodium - decrease | 5 participants | — |
| Pramipexole Extended Release (PPX ER) | Possible Clinically Significant Abnormal Laboratory Parameters | Triglyceride - increase | 9 participants | — |
| Pramipexole Extended Release (PPX ER) | Possible Clinically Significant Abnormal Laboratory Parameters | Chloride - decrease | 2 participants | — |
| Pramipexole Extended Release (PPX ER) | Possible Clinically Significant Abnormal Laboratory Parameters | Potassium - increase | 3 participants | — |
| Pramipexole Extended Release (PPX ER) | Possible Clinically Significant Abnormal Laboratory Parameters | Uric acid - increase | 3 participants | — |
| Pramipexole Extended Release (PPX ER) | Possible Clinically Significant Abnormal Laboratory Parameters | Cholesterol, total - increase | 0 participants | — |
| Pramipexole Extended Release (PPX ER) | Possible Clinically Significant Abnormal Laboratory Parameters | White blood cell ct. - decrease | 1 participants | — |
| Pramipexole Extended Release (PPX ER) | Possible Clinically Significant Abnormal Laboratory Parameters | Haemoglobin - decrease | 11 participants | — |
| Pramipexole Extended Release (PPX ER) | Possible Clinically Significant Abnormal Laboratory Parameters | Glucose - increase | 1 participants | — |
| Pramipexole Extended Release (PPX ER) | Possible Clinically Significant Abnormal Laboratory Parameters | Neut., poly (segs) - decrease | 2 participants | — |
| Pramipexole Extended Release (PPX ER) | Possible Clinically Significant Abnormal Laboratory Parameters | Haematocrit - decrease | 4 participants | 9.8 |
| Pramipexole Extended Release (PPX ER) | Possible Clinically Significant Abnormal Laboratory Parameters | Glucose - decrease | 3 participants | — |
| Pramipexole Extended Release (PPX ER) | Possible Clinically Significant Abnormal Laboratory Parameters | Eosinophils - increase | 6 participants | — |
| Pramipexole Extended Release (PPX ER) | Possible Clinically Significant Abnormal Laboratory Parameters | Creatinine - increase | 0 participants | — |
| Pramipexole Immediate Release (PPX IR) | Possible Clinically Significant Abnormal Laboratory Parameters | Alkaline phosphatase - increase | 1 participants | — |
| Pramipexole Immediate Release (PPX IR) | Possible Clinically Significant Abnormal Laboratory Parameters | Haematocrit - decrease | 3 participants | 10.1 |
| Pramipexole Immediate Release (PPX IR) | Possible Clinically Significant Abnormal Laboratory Parameters | Haemoglobin - decrease | 6 participants | — |
| Pramipexole Immediate Release (PPX IR) | Possible Clinically Significant Abnormal Laboratory Parameters | Red blood cell ct. - decrease | 0 participants | — |
| Pramipexole Immediate Release (PPX IR) | Possible Clinically Significant Abnormal Laboratory Parameters | White blood cell ct. - decrease | 0 participants | — |
| Pramipexole Immediate Release (PPX IR) | Possible Clinically Significant Abnormal Laboratory Parameters | Neut., poly (segs) - decrease | 0 participants | — |
| Pramipexole Immediate Release (PPX IR) | Possible Clinically Significant Abnormal Laboratory Parameters | Eosinophils - increase | 3 participants | — |
| Pramipexole Immediate Release (PPX IR) | Possible Clinically Significant Abnormal Laboratory Parameters | Neut., poly (segs), absol. - decrease | 0 participants | — |
| Pramipexole Immediate Release (PPX IR) | Possible Clinically Significant Abnormal Laboratory Parameters | Sodium - decrease | 5 participants | — |
| Pramipexole Immediate Release (PPX IR) | Possible Clinically Significant Abnormal Laboratory Parameters | Potassium - increase | 1 participants | — |
| Pramipexole Immediate Release (PPX IR) | Possible Clinically Significant Abnormal Laboratory Parameters | Chloride - decrease | 0 participants | — |
| Pramipexole Immediate Release (PPX IR) | Possible Clinically Significant Abnormal Laboratory Parameters | GGT - increase | 1 participants | — |
| Pramipexole Immediate Release (PPX IR) | Possible Clinically Significant Abnormal Laboratory Parameters | Glucose - decrease | 0 participants | — |
| Pramipexole Immediate Release (PPX IR) | Possible Clinically Significant Abnormal Laboratory Parameters | Glucose - increase | 1 participants | — |
| Pramipexole Immediate Release (PPX IR) | Possible Clinically Significant Abnormal Laboratory Parameters | Cholesterol, total - increase | 0 participants | — |
| Pramipexole Immediate Release (PPX IR) | Possible Clinically Significant Abnormal Laboratory Parameters | Creatinine - increase | 0 participants | — |
| Pramipexole Immediate Release (PPX IR) | Possible Clinically Significant Abnormal Laboratory Parameters | Triglyceride - increase | 3 participants | — |
| Pramipexole Immediate Release (PPX IR) | Possible Clinically Significant Abnormal Laboratory Parameters | Uric acid - increase | 1 participants | — |
| Placebo | Possible Clinically Significant Abnormal Laboratory Parameters | Haemoglobin - decrease | 1 participants | — |
| Placebo | Possible Clinically Significant Abnormal Laboratory Parameters | GGT - increase | 0 participants | — |
| Placebo | Possible Clinically Significant Abnormal Laboratory Parameters | Neut., poly (segs) - decrease | 0 participants | — |
| Placebo | Possible Clinically Significant Abnormal Laboratory Parameters | Uric acid - increase | 2 participants | — |
| Placebo | Possible Clinically Significant Abnormal Laboratory Parameters | Glucose - decrease | 0 participants | — |
| Placebo | Possible Clinically Significant Abnormal Laboratory Parameters | White blood cell ct. - decrease | 0 participants | — |
| Placebo | Possible Clinically Significant Abnormal Laboratory Parameters | Creatinine - increase | 1 participants | — |
| Placebo | Possible Clinically Significant Abnormal Laboratory Parameters | Glucose - increase | 0 participants | — |
| Placebo | Possible Clinically Significant Abnormal Laboratory Parameters | Red blood cell ct. - decrease | 0 participants | — |
| Placebo | Possible Clinically Significant Abnormal Laboratory Parameters | Haematocrit - decrease | 1 participants | 10.7 |
| Placebo | Possible Clinically Significant Abnormal Laboratory Parameters | Potassium - increase | 0 participants | — |
| Placebo | Possible Clinically Significant Abnormal Laboratory Parameters | Sodium - decrease | 0 participants | — |
| Placebo | Possible Clinically Significant Abnormal Laboratory Parameters | Cholesterol, total - increase | 1 participants | — |
| Placebo | Possible Clinically Significant Abnormal Laboratory Parameters | Chloride - decrease | 0 participants | — |
| Placebo | Possible Clinically Significant Abnormal Laboratory Parameters | Neut., poly (segs), absol. - decrease | 0 participants | — |
| Placebo | Possible Clinically Significant Abnormal Laboratory Parameters | Triglyceride - increase | 5 participants | — |
| Placebo | Possible Clinically Significant Abnormal Laboratory Parameters | Alkaline phosphatase - increase | 0 participants | — |
| Placebo | Possible Clinically Significant Abnormal Laboratory Parameters | Eosinophils - increase | 3 participants | — |
Secondary
UPDRS II+III Responder Rate (at Least 20% Improvement)
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.
Time frame: after 33 weeks treatment
Population: Full Analysis Set, all randomized patients, received at least one dose of study drug and provided any post baseline efficacy assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pramipexole Extended Release (PPX ER) | UPDRS II+III Responder Rate (at Least 20% Improvement) | 68.5 percentage of responders |
| Pramipexole Immediate Release (PPX IR) | UPDRS II+III Responder Rate (at Least 20% Improvement) | 65.7 percentage of responders |
| Placebo | UPDRS II+III Responder Rate (at Least 20% Improvement) | 48.5 percentage of responders |
Secondary
UPDRS Part I Change From Baseline
UPDRS I evaluates mentation behaviour and mood with a total score of 0-16. Decrease in the scores means improvement
Time frame: baseline and after 33 weeks treatment
Population: Full Analysis Set with (LOCF), all randomized patients, received at least one dose of study drug and provided any post baseline efficacy assessment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole Extended Release (PPX ER) | UPDRS Part I Change From Baseline | 0.0 units on a scale |
| Pramipexole Immediate Release (PPX IR) | UPDRS Part I Change From Baseline | 0.0 units on a scale |
| Placebo | UPDRS Part I Change From Baseline | 0.0 units on a scale |
Secondary
UPDRS Part III Total Score
UPDRS III is the result of a motor examination with the scores 0-108. A decrease in the scores means improvement
Time frame: after 33 weeks treatment
Population: Full Analysis Set, all randomized patients, received at least one dose of study drug and provided any post baseline efficacy assessment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pramipexole Extended Release (PPX ER) | UPDRS Part III Total Score | -6.4 units on a scale |
| Pramipexole Immediate Release (PPX IR) | UPDRS Part III Total Score | -6.4 units on a scale |
| Placebo | UPDRS Part III Total Score | -2.8 units on a scale |
Secondary
UPDRS Part II Total Score
UPDRS II evaluates activities of daily living in a score 0-52. Decrease of the score means improvement
Time frame: after 33 weeks treatment
Population: Full Analysis Set, all randomized patients, received at least one dose of study drug and provided any post baseline efficacy assessment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Pramipexole Extended Release (PPX ER) | UPDRS Part II Total Score | -2.2 units on a scale |
| Pramipexole Immediate Release (PPX IR) | UPDRS Part II Total Score | -2.4 units on a scale |
| Placebo | UPDRS Part II Total Score | -0.9 units on a scale |