Parkinson Disease
Conditions
Brief summary
The general aim of this trial is to determine the efficacy (as measured by the change from baseline to the end of the maintenance phase in the total score for Unified Parkinsons Disease Rating Scale Parts II and III combined), safety, and tolerability of pramipexole ER, in daily doses from 0.375 milligram to 4.5 milligram once a day, in comparison to placebo, in Levodopa combined with a Dopa-Decarboxylase-inhibitor treated Parkinson patients with advanced Parkinsons Disease and motor fluctuations. In addition, a numerical comparison of the efficacy of pramipexole extended release versus pramipexole immediate release will be done. The efficacy of pramipexole immediate release will also be compared to placebo, for assay sensitivity.
Interventions
Sponsors
Boehringer Ingelheim
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
32 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patient with advanced idiopathic Parkinsons disease confirmed by at least two of the following signs: resting tremor, bradykinesia, rigidity. 2. Parkinsons disease diagnosed for at least 2 years. 3. Patients 30 years of age or older at the time of diagnosis. 4. Modified Hoehn and Yahr stage of 2 to 4 at on-time. 5. Treatment with standard or controlled release Levodopa combined with a Dopa-Decarboxylase-inhibitor, or with Levodopa combined with a Dopa-Decarboxylase-inhibitor/entacapone, at an optimised dose according to investigators judgement, this dose being stable for at least 4 weeks prior to baseline visit. 6. Motor fluctuations, with at least 2 cumulative hours of off-time every day during waking hours (documented on a patient diary completed for 2 consecutive days before baseline visit). 7. Patient willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. In particular, after training, it has to be documented at baseline visit that the patient is able to recognise the off-time and on-time periods during waking hours and that the patient (or a family member or a guardian) is able to record them accurately in the patient diary. 8. Signed informed consent obtained before any study procedures are carried out (in accordance with International Conference on Harmonisation-Good Clinical Practice guidelines and local legislation).
Exclusion criteria
1. Atypical parkinsonian syndromes due to drugs, metabolic disorders, encephalitis or degenerative diseases 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 edition criteria that could prevent compliance or completion of the study and/or put the patient at risk if he/she takes part in the study 4. History of psychosis, except history of drug induced hallucinations 5. History of deep brain stimulation 6. Clinically significant Electrocardiogram abnormalities at screening visit 7. Clinically significant hypotension and/or symptomatic orthostatic hypotension at screening or baseline visit 8. Malignant melanoma or history of previously treated malignant melanoma 9. 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 10. Pregnancy or breast-feeding 11. Sexually active female of childbearing potential not using a medically approved method of birth control for at least one month prior to the screening visit and throughout the study period 12. Serum levels of Aspartate Aminotransferase (Serum Glutamic-Oxaloacetic Transaminase), Alanine Aminotransferase (Serum Glutamic Pyruvic Transaminase), alkaline phosphatases or bilirubin \> 2 Upper Limit of Normal 13. Patients with a creatinine clearance \< 50 millilitres/minute 14. Any dopamine agonist (including pramipexole) within 4 weeks prior to baseline visit 15. Any medication with central dopaminergic antagonist activity within 4 weeks prior to the baseline visit 16. Any of the following drugs within 4 weeks prior to 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 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 (whichever is longer) prior to baseline visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Score at Week 18 | baseline and week 18 | UPDRS II+III total score on Full Analysis Set (FAS)with LOCF (Last observation carried forward), week 18 - baseline, UPDRS II+III ranging from 0 (normal) to 160 (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Percentage On-time Without Dyskinesia at Week 18 | baseline and week 18 | Percentage on-time based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep. |
| Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia at Week 18 | baseline and week 18 | Percentage on-time with non-troublesome dyskinesia based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep. |
| Change From Baseline in Percentage On-time With Troublesome Dyskinesia at Week 18 | baseline and week 18 | Percentage on-time with troublesome dyskinesia based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). On-time describes a period when the patient has no symptoms of off-time and is not asleep. |
| Change From Baseline in 11-point Likert Scale for Pain Related to PD at Week 18 | baseline and week 18 | Likert scale is a method used for the measurement of pain. The patients were asked to rate their pain related to PD by ticking the number that best described their pain on the average in the previous week, from zero for no pain to ten for unbearable pain. |
| Clinical Global Impression - Global Improvement (CGI-I) Responder | after 18 weeks of treatment | CGI-I scores ranging from '1' (very much improved) to '7' (very much worse), CGI-I responder have scoring of 1 or 2 (at least much improved) |
| Response in Patient Global Impression (PGI-I) | after 18 weeks of treatment | PGI-I scores ranging from '1' (very much better) to '7' (very much worse), PGI-I responder have scoring 1 or 2 (at least much better) |
| Change From Baseline in UPDRS I Score After 18 Weeks | baseline and 18 weeks | UPDRS I ranging from 0 (normal) to 16 (severe). UPDRS I measures Mentation, Behavior and Mood |
| Change From Baseline in Percentage Off-time at Week 18 | baseline and week 18 | Percentage off-time based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). Off-time describes a period when the patient experiences increased parkinsonian symptoms (e.g. immobility or inability to move with ease). |
| Change From Baseline in UPDRS III Score After 18 Weeks | baseline and 18 weeks | UPDRS III ranging from 0 (normal) to 108 (severe). UPDRS part III measures motor symptoms |
| Change From Baseline in UPDRS IV Score After 18 Weeks | baseline and 18 weeks | UPDRS IV ranging from 0 (normal) to 23 (severe). UPDRS IV measures complications of therapy |
| Change From Baseline in Beck's Depression Inventory (BDI) After 18 Weeks | baseline and 18 weeks | ranging from 0 (best case) to 63 (worst case) |
| Change From Baseline in Parkinson's Disease Sleep Scale (PDSS) After 18 Weeks | baseline and 18 weeks | ranging from 0 (worst case) to 150 (best case) |
| Change From Baseline in Parkinson's Disease Quality of Life Questionnaire 39 After 18 Weeks | baseline and 18 weeks | Ranging from 0 (best case) to 156 (worst case) |
| Change From Baseline in European Quality of Life (EuroQol) Scale After 18 Weeks | baseline and 18 weeks | ranging from 0 (worst case) to 100 (best case) |
| Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | baseline and week 18 | — |
| Change From Baseline in UPDRS II Score After 18 Weeks, Average at on and Off-period | baseline and 18 weeks | UPDRS II ranging from 0 (normal) to 52 (severe). UPDRS Part II is calculated as the average of UPDRS part II at on and UPDRS part II at off-period for each of the 13 activities. |
Countries
Austria, Czechia, Hungary, India, Italy, Philippines, Poland, Russia, Slovakia, South Korea, Spain, Sweden, Ukraine, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pramipexole ER Pramipexole Extended Release (ER) (tablets of 0.375mg, 0.75mg, 1.5mg, 3.0mg or 4.5mg), dose: 0.375 mg, 0.75mg, 1.5mg, 2.25mg, 3.0mg, 3.75mg, or 4.5mg, mode of administration: Per os, once a day, in the morning | 164 |
| Pramipexole IR Pramipexole Immediate Release (IR) (tablets of 0.125mg, 0.25mg, 0.5mg, 1.0mg and 1.5mg), dose: 0.375mg, 0.75mg, 1.5mg, 2.25mg, 3.0mg, 3.75mg, or 4.5mg, mode of administration: Per os, in equally divided doses 3 times per day | 175 |
| Placebo Matching Placebo to Pramipexole IR (tablets of 0.125mg, 0.25mg, 0.5mg, 1.0mg and 1.5mg), dose: 0.375mg, 0.75mg, 1.5mg, 2.25mg, 3.0mg, 3.75mg, or 4.5mg, mode of administration: Per os, in equally divided doses 3 times per day
Matching Placebo to Pramipexole ER (tablets of 0.375mg, 0.75mg, 1.5mg, 3.0mg or 4.5mg), dose: 0.375 mg, 0.75mg, 1.5mg, 2.25mg, 3.0mg, 3.75mg, or 4.5mg, mode of administration: Per os, once a day, in the morning | 178 |
| Total | 517 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 8 | 8 | 7 |
| Overall Study | Lack of Efficacy | 2 | 0 | 3 |
| Overall Study | Lost to Follow-up | 3 | 2 | 2 |
| Overall Study | Not treated | 1 | 0 | 0 |
| Overall Study | patient did not meet inclusion criteria | 1 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 1 | 6 |
Baseline characteristics
| Characteristic | Pramipexole ER | Pramipexole IR | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 61.6 years STANDARD_DEVIATION 9.7 | 62.0 years STANDARD_DEVIATION 10.3 | 60.9 years STANDARD_DEVIATION 9.7 | 61.5 years STANDARD_DEVIATION 9.9 |
| Sex: Female, Male Female | 72 Participants | 77 Participants | 84 Participants | 233 Participants |
| Sex: Female, Male Male | 92 Participants | 98 Participants | 94 Participants | 284 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 | 74 / 178 | 73 / 164 | 90 / 175 |
| serious Total, serious adverse events | 15 / 178 | 8 / 164 | 11 / 175 |
Outcome results
Primary
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Score at Week 18
UPDRS II+III total score on Full Analysis Set (FAS)with LOCF (Last observation carried forward), week 18 - baseline, UPDRS II+III ranging from 0 (normal) to 160 (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms
Time frame: baseline and week 18
Population: Full analysis set (FAS 1) population = 507 patients FAS 1 defined as all patients who were dispensed study medication, were documented to have at least one dose of study medication, were treated for 18 weeks (or had prematurely discontinued treatment prior to week 18) and provided baseline and any on-drug post-baseline efficacy assessment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Score at Week 18 | -11.0 Percentage of change from baseline | Standard Error 1 |
| Pramipexole IR | Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Score at Week 18 | -12.8 Percentage of change from baseline | Standard Error 0.9 |
| Placebo | Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Score at Week 18 | -6.1 Percentage of change from baseline | Standard Error 0.9 |
Comparison: ANCOVA with factors treatment, pooled country and covariate baselinep-value: 0.000195% CI: [2.4, 7.4]ANCOVA
Comparison: ANCOVA with factors treatment, pooled country and covariate baselinep-value: <0.000195% CI: [4.2, 9.1]ANCOVA
Secondary
Change From Baseline in 11-point Likert Scale for Pain Related to PD at Week 18
Likert scale is a method used for the measurement of pain. The patients were asked to rate their pain related to PD by ticking the number that best described their pain on the average in the previous week, from zero for no pain to ten for unbearable pain.
Time frame: baseline and week 18
Population: Full analysis set (FAS 1) population with last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in 11-point Likert Scale for Pain Related to PD at Week 18 | -0.4 units on a scale | Standard Error 0.2 |
| Pramipexole IR | Change From Baseline in 11-point Likert Scale for Pain Related to PD at Week 18 | -1.0 units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in 11-point Likert Scale for Pain Related to PD at Week 18 | -0.3 units on a scale | Standard Error 0.2 |
Secondary
Change From Baseline in Beck's Depression Inventory (BDI) After 18 Weeks
ranging from 0 (best case) to 63 (worst case)
Time frame: baseline and 18 weeks
Population: Full analysis set (FAS 1) population with last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in Beck's Depression Inventory (BDI) After 18 Weeks | -3.2 Units on a scale | Standard Error 0.5 |
| Pramipexole IR | Change From Baseline in Beck's Depression Inventory (BDI) After 18 Weeks | -4.0 Units on a scale | Standard Error 0.5 |
| Placebo | Change From Baseline in Beck's Depression Inventory (BDI) After 18 Weeks | -2.8 Units on a scale | Standard Error 0.5 |
Secondary
Change From Baseline in European Quality of Life (EuroQol) Scale After 18 Weeks
ranging from 0 (worst case) to 100 (best case)
Time frame: baseline and 18 weeks
Population: Full analysis set (FAS 1) population with last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in European Quality of Life (EuroQol) Scale After 18 Weeks | 5.8 Units on a scale | Standard Error 1.4 |
| Pramipexole IR | Change From Baseline in European Quality of Life (EuroQol) Scale After 18 Weeks | 7.6 Units on a scale | Standard Error 1.3 |
| Placebo | Change From Baseline in European Quality of Life (EuroQol) Scale After 18 Weeks | 4.3 Units on a scale | Standard Error 1.3 |
Secondary
Change From Baseline in Parkinson's Disease Quality of Life Questionnaire 39 After 18 Weeks
Ranging from 0 (best case) to 156 (worst case)
Time frame: baseline and 18 weeks
Population: Full analysis set (FAS 1) population with last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in Parkinson's Disease Quality of Life Questionnaire 39 After 18 Weeks | -9.1 Units on a scale | Standard Error 1.9 |
| Pramipexole IR | Change From Baseline in Parkinson's Disease Quality of Life Questionnaire 39 After 18 Weeks | -13.1 Units on a scale | Standard Error 1.8 |
| Placebo | Change From Baseline in Parkinson's Disease Quality of Life Questionnaire 39 After 18 Weeks | -6.2 Units on a scale | Standard Error 1.8 |
Secondary
Change From Baseline in Parkinson's Disease Sleep Scale (PDSS) After 18 Weeks
ranging from 0 (worst case) to 150 (best case)
Time frame: baseline and 18 weeks
Population: Full analysis set (FAS 1) population with last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in Parkinson's Disease Sleep Scale (PDSS) After 18 Weeks | 8.1 Units on a scale | Standard Error 1.8 |
| Pramipexole IR | Change From Baseline in Parkinson's Disease Sleep Scale (PDSS) After 18 Weeks | 8.9 Units on a scale | Standard Error 1.7 |
| Placebo | Change From Baseline in Parkinson's Disease Sleep Scale (PDSS) After 18 Weeks | 4.9 Units on a scale | Standard Error 1.7 |
Secondary
Change From Baseline in Percentage Off-time at Week 18
Percentage off-time based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). Off-time describes a period when the patient experiences increased parkinsonian symptoms (e.g. immobility or inability to move with ease).
Time frame: baseline and week 18
Population: Full analysis set (FAS 1) population with last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in Percentage Off-time at Week 18 | -13.3 Percentage of off-time | Standard Error 1.4 |
| Pramipexole IR | Change From Baseline in Percentage Off-time at Week 18 | -15.9 Percentage of off-time | Standard Error 1.3 |
| Placebo | Change From Baseline in Percentage Off-time at Week 18 | -8.8 Percentage of off-time | Standard Error 1.3 |
Comparison: ANCOVA with factors treatment, pooled country and covariate baselinep-value: 0.012295% CI: [1, 7.9]ANCOVA
Comparison: ANCOVA with factors treatment, pooled country and covariate baselinep-value: <0.000195% CI: [3.7, 10.5]ANCOVA
Secondary
Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia at Week 18
Percentage on-time with non-troublesome dyskinesia based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.
Time frame: baseline and week 18
Population: Full analysis set (FAS 1) population with last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia at Week 18 | 1.9 Percentage of on-time | Standard Error 1.2 |
| Pramipexole IR | Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia at Week 18 | 3.9 Percentage of on-time | Standard Error 1.2 |
| Placebo | Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia at Week 18 | 1.0 Percentage of on-time | Standard Error 1.2 |
Secondary
Change From Baseline in Percentage On-time Without Dyskinesia at Week 18
Percentage on-time based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.
Time frame: baseline and week 18
Population: Full analysis set (FAS 1) population with last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in Percentage On-time Without Dyskinesia at Week 18 | 11.9 Percentage of on-time without dyskinesia | Standard Error 1.7 |
| Pramipexole IR | Change From Baseline in Percentage On-time Without Dyskinesia at Week 18 | 12.6 Percentage of on-time without dyskinesia | Standard Error 1.7 |
| Placebo | Change From Baseline in Percentage On-time Without Dyskinesia at Week 18 | 8.9 Percentage of on-time without dyskinesia | Standard Error 1.6 |
Secondary
Change From Baseline in Percentage On-time With Troublesome Dyskinesia at Week 18
Percentage on-time with troublesome dyskinesia based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.
Time frame: baseline and week 18
Population: Full analysis set (FAS 1) population with last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in Percentage On-time With Troublesome Dyskinesia at Week 18 | -0.8 Percentage of on-time | Standard Error 0.5 |
| Pramipexole IR | Change From Baseline in Percentage On-time With Troublesome Dyskinesia at Week 18 | -0.8 Percentage of on-time | Standard Error 0.5 |
| Placebo | Change From Baseline in Percentage On-time With Troublesome Dyskinesia at Week 18 | -1.0 Percentage of on-time | Standard Error 0.5 |
Secondary
Change From Baseline in UPDRS III Score After 18 Weeks
UPDRS III ranging from 0 (normal) to 108 (severe). UPDRS part III measures motor symptoms
Time frame: baseline and 18 weeks
Population: Full analysis set (FAS 1) population with last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in UPDRS III Score After 18 Weeks | -8.3 Units on a scale | Standard Error 0.7 |
| Pramipexole IR | Change From Baseline in UPDRS III Score After 18 Weeks | -9.2 Units on a scale | Standard Error 0.7 |
| Placebo | Change From Baseline in UPDRS III Score After 18 Weeks | -4.3 Units on a scale | Standard Error 0.7 |
Secondary
Change From Baseline in UPDRS II Score After 18 Weeks, Average at on and Off-period
UPDRS II ranging from 0 (normal) to 52 (severe). UPDRS Part II is calculated as the average of UPDRS part II at on and UPDRS part II at off-period for each of the 13 activities.
Time frame: baseline and 18 weeks
Population: Full analysis set (FAS 1) population with last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in UPDRS II Score After 18 Weeks, Average at on and Off-period | -2.7 Units on a scale | Standard Error 0.3 |
| Pramipexole IR | Change From Baseline in UPDRS II Score After 18 Weeks, Average at on and Off-period | -3.6 Units on a scale | Standard Error 0.3 |
| Placebo | Change From Baseline in UPDRS II Score After 18 Weeks, Average at on and Off-period | -1.9 Units on a scale | Standard Error 0.3 |
Secondary
Change From Baseline in UPDRS I Score After 18 Weeks
UPDRS I ranging from 0 (normal) to 16 (severe). UPDRS I measures Mentation, Behavior and Mood
Time frame: baseline and 18 weeks
Population: Full analysis set (FAS 1) population with last observation carried forward (LOCF).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole ER | Change From Baseline in UPDRS I Score After 18 Weeks | 0 Units on a scale |
| Pramipexole IR | Change From Baseline in UPDRS I Score After 18 Weeks | 0 Units on a scale |
| Placebo | Change From Baseline in UPDRS I Score After 18 Weeks | 0 Units on a scale |
Secondary
Change From Baseline in UPDRS IV Score After 18 Weeks
UPDRS IV ranging from 0 (normal) to 23 (severe). UPDRS IV measures complications of therapy
Time frame: baseline and 18 weeks
Population: Full analysis set (FAS 1) population with last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole ER | Change From Baseline in UPDRS IV Score After 18 Weeks | -0.8 Units on a scale | Standard Error 0.2 |
| Pramipexole IR | Change From Baseline in UPDRS IV Score After 18 Weeks | -0.9 Units on a scale | Standard Error 0.2 |
| Placebo | Change From Baseline in UPDRS IV Score After 18 Weeks | -0.6 Units on a scale | Standard Error 0.2 |
Secondary
Clinical Global Impression - Global Improvement (CGI-I) Responder
CGI-I scores ranging from '1' (very much improved) to '7' (very much worse), CGI-I responder have scoring of 1 or 2 (at least much improved)
Time frame: after 18 weeks of treatment
Population: Full analysis set (FAS 1) population with last observation carried forward (LOCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pramipexole ER | Clinical Global Impression - Global Improvement (CGI-I) Responder | Responder | 78 Participants |
| Pramipexole ER | Clinical Global Impression - Global Improvement (CGI-I) Responder | Non-Responder | 82 Participants |
| Pramipexole IR | Clinical Global Impression - Global Improvement (CGI-I) Responder | Responder | 88 Participants |
| Pramipexole IR | Clinical Global Impression - Global Improvement (CGI-I) Responder | Non-Responder | 81 Participants |
| Placebo | Clinical Global Impression - Global Improvement (CGI-I) Responder | Responder | 56 Participants |
| Placebo | Clinical Global Impression - Global Improvement (CGI-I) Responder | Non-Responder | 115 Participants |
Secondary
Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology)
Time frame: baseline and week 18
Population: Treated set (TS 1) population: defined as all patients who were dispensed study medication, were documented to have at least one dose of study medication and were treated for 18 weeks (or had discontinued treatment prior to week 18). Data limited to visit 8 (or V11 in case of premature discontinuation before visit 8).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pramipexole ER | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Blood pressure - increase | 1 participants |
| Pramipexole ER | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Glucose - increase | 0 participants |
| Pramipexole ER | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Sodium - decrease | 0 participants |
| Pramipexole ER | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Red blood cell ct - decrease | 1 participants |
| Pramipexole ER | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Glucose - decrease | 1 participants |
| Pramipexole ER | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | GGT - increase | 1 participants |
| Pramipexole ER | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Haematocrit - decrease | 2 participants |
| Pramipexole ER | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Haemoglobin - decrease | 2 participants |
| Pramipexole ER | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Weight - decrease | 0 participants |
| Pramipexole ER | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Eosinophils - Increase | 3 participants |
| Pramipexole ER | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Blood pressure - decrease | 0 participants |
| Pramipexole ER | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Triglyceride - increase | 2 participants |
| Pramipexole ER | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Neut.,poly. (segs),absol. - decrease | 0 participants |
| Pramipexole IR | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | GGT - increase | 0 participants |
| Pramipexole IR | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Haematocrit - decrease | 3 participants |
| Pramipexole IR | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Haemoglobin - decrease | 5 participants |
| Pramipexole IR | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Red blood cell ct - decrease | 0 participants |
| Pramipexole IR | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Eosinophils - Increase | 2 participants |
| Pramipexole IR | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Neut.,poly. (segs),absol. - decrease | 1 participants |
| Pramipexole IR | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Sodium - decrease | 2 participants |
| Pramipexole IR | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Glucose - decrease | 0 participants |
| Pramipexole IR | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Glucose - increase | 2 participants |
| Pramipexole IR | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Triglyceride - increase | 3 participants |
| Pramipexole IR | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Weight - decrease | 3 participants |
| Pramipexole IR | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Blood pressure - increase | 2 participants |
| Pramipexole IR | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Blood pressure - decrease | 0 participants |
| Placebo | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Glucose - increase | 1 participants |
| Placebo | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Eosinophils - Increase | 1 participants |
| Placebo | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Blood pressure - increase | 0 participants |
| Placebo | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Triglyceride - increase | 5 participants |
| Placebo | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Red blood cell ct - decrease | 1 participants |
| Placebo | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Haematocrit - decrease | 1 participants |
| Placebo | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Weight - decrease | 1 participants |
| Placebo | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | GGT - increase | 1 participants |
| Placebo | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Sodium - decrease | 0 participants |
| Placebo | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Haemoglobin - decrease | 3 participants |
| Placebo | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Glucose - decrease | 1 participants |
| Placebo | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Neut.,poly. (segs),absol. - decrease | 0 participants |
| Placebo | Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) | Blood pressure - decrease | 1 participants |
Secondary
Response in Patient Global Impression (PGI-I)
PGI-I scores ranging from '1' (very much better) to '7' (very much worse), PGI-I responder have scoring 1 or 2 (at least much better)
Time frame: after 18 weeks of treatment
Population: Full analysis set (FAS 1) population with last observation carried forward (LOCF).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pramipexole ER | Response in Patient Global Impression (PGI-I) | Responder | 60 Participants |
| Pramipexole ER | Response in Patient Global Impression (PGI-I) | Non-Responder | 101 Participants |
| Pramipexole IR | Response in Patient Global Impression (PGI-I) | Responder | 76 Participants |
| Pramipexole IR | Response in Patient Global Impression (PGI-I) | Non-Responder | 96 Participants |
| Placebo | Response in Patient Global Impression (PGI-I) | Responder | 47 Participants |
| Placebo | Response in Patient Global Impression (PGI-I) | Non-Responder | 127 Participants |