Phase 3
Completed N=518
Pivotal Study in Advanced Parkinsons Disease Patients
Source: ClinicalTrials.gov NCT00466167 ↗Enrolled (actual)
518
Serious AEs
6.6%
Results posted
Feb 2010
Primary outcomePrimary: Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Score at Week 18 — -11.0; -12.8; -6.1 Percentage of change from baseline — p=0.0001
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Score at Week 18 |
-11.0; -12.8; -6.1 | 0.0001 sig |
| SECONDARY Change From Baseline in Percentage Off-time at Week 18 |
-13.3; -15.9; -8.8 | 0.0122 sig |
| SECONDARY Change From Baseline in Percentage On-time Without Dyskinesia at Week 18 |
11.9; 12.6; 8.9 | — |
| SECONDARY Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia at Week 18 |
1.9; 3.9; 1.0 | — |
| SECONDARY Change From Baseline in Percentage On-time With Troublesome Dyskinesia at Week 18 |
-0.8; -0.8; -1.0 | — |
| SECONDARY Clinical Global Impression - Global Improvement (CGI-I) Responder |
78; 88; 56; 82; 81; 115 | — |
| SECONDARY Response in Patient Global Impression (PGI-I) |
60; 76; 47; 101; 96; 127 | — |
| SECONDARY Change From Baseline in UPDRS I Score After 18 Weeks |
0; 0; 0 | — |
| SECONDARY Change From Baseline in UPDRS II Score After 18 Weeks, Average at on and Off-period |
-2.7; -3.6; -1.9 | — |
| SECONDARY Change From Baseline in UPDRS III Score After 18 Weeks |
-8.3; -9.2; -4.3 | — |
| SECONDARY Change From Baseline in UPDRS IV Score After 18 Weeks |
-0.8; -0.9; -0.6 | — |
| SECONDARY Change From Baseline in Beck's Depression Inventory (BDI) After 18 Weeks |
-3.2; -4.0; -2.8 | — |
| SECONDARY Change From Baseline in Parkinson's Disease Sleep Scale (PDSS) After 18 Weeks |
8.1; 8.9; 4.9 | — |
| SECONDARY Change From Baseline in Parkinson's Disease Quality of Life Questionnaire 39 After 18 Weeks |
-9.1; -13.1; -6.2 | — |
| SECONDARY Change From Baseline in European Quality of Life (EuroQol) Scale After 18 Weeks |
5.8; 7.6; 4.3 | — |
| SECONDARY Change From Baseline in 11-point Likert Scale for Pain Related to PD at Week 18 |
-0.4; -1.0; -0.3 | — |
| SECONDARY Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology) |
2; 3; 1; 2; 5; 3 | — |
Eligibility Criteria
Inclusion Criteria
- Male or female patient with advanced idiopathic Parkinsons disease confirmed by at least two of the following signs: resting tremor, bradykinesia, rigidity.
- Parkinsons disease diagnosed for at least 2 years.
- Patients 30 years of age or older at the time of diagnosis.
- Modified Hoehn and Yahr stage of 2 to 4 at on-time.
- 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.
- 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).
- 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.
- 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
- Atypical parkinsonian syndromes due to drugs, metabolic disorders, encephalitis or degenerative diseases
- Dementia, as defined by a Mini-Mental State Exam score 2 Upper Limit of Normal
- Patients with a creatinine clearance < 50 millilitres/minute
- Any dopamine agonist (including pramipexole) within 4 weeks prior to baseline visit
- Any medication with central dopaminergic antagonist activity within 4 weeks prior to the baseline visit
- Any of the following drugs within 4 weeks prior to baseline visit: methylphenidate, cinnarizine, amphetamines
- Flunarizine within 3 months prior to baseline visit
- Known hypersensitivity to pramipexole or its excipients
- Drug abuse according to investigators judgement, within 2 years prior to screening
- 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
Data sourced from ClinicalTrials.gov (NCT00466167). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.