Phase 3
Completed N=391
Long-term Safety Study of Open-label Pramipexole ER in Patients With Advanced PD
Source: ClinicalTrials.gov NCT00577460 ↗Enrolled (actual)
391
Serious AEs
10.0%
Results posted
Jul 2011
Primary outcomePrimary: Percentage of Patients With Adverse Events, Adverse Drug Reactions, Serious Adverse Events — 85.3; 83.7; 79.9; 52.7 Percentage of participants
Summary
The general aim of this study is to obtain long-term safety and tolerability data on pramipexole extended release (ER), in daily doses from 0.375mg to 4.5mg once daily (qd), in patients who have previously completed a pramipexole double-blind study in advanced Parkinson's disease (PD) (248.525 trial).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Patients With Adverse Events, Adverse Drug Reactions, Serious Adverse Events |
85.3; 83.7; 79.9; 52.7; 48.8; 45.3 | — |
| SECONDARY Patients Successfully Switched From Pramipexole (PPX) IR or ER to ER Assessed on UPDRS II+III |
88; 106 | — |
| SECONDARY UPDRS II+III Change From Open Label (OL) Baseline |
-3.6; 1.1; 2.5 | 0.0039 sig |
| SECONDARY Number of Participants With UPDRS II+III Response |
35; 30; 31 | — |
| SECONDARY Number of Patients Successfully Switched From PPX IR or ER to ER Assessed on Off-time |
57; 70 | — |
| SECONDARY Percentage Off Time During Waking Hours Total Score: Change From Baseline |
-1.5; -0.3; 1.7 | 0.5590 |
| SECONDARY Number of Participants With Response in Percentage Off Time During Waking Hours |
35; 40; 28; 103 | — |
| SECONDARY Percentage on Time Without Dyskinesia During Waking Hours: Change From Baseline After 80 Weeks |
-1.6; 2.9; -2.0 | 0.1073 |
| SECONDARY Percentage on Time With Non Troublesome Dyskinesia During Waking Hours: Change From Baseline After 80 Weeks |
3.8; -2.7; 0.2 | 0.0009 sig |
| SECONDARY Percentage on Time Without Dyskinesia or With Non Troublesome Dyskinesia During Waking Hours: Change From Baseline After 80 Weeks |
1.8; 0.7; -0.9 | 0.6434 |
| SECONDARY Percentage on Time With Troublesome Dyskinesia During Waking Hours: Change From Baseline After 80 Weeks |
-0.4; -0.3; -0.7 | 0.9741 |
| SECONDARY Number of Participants With Response in CGI-I |
50; 106; 114; 270 | — |
| SECONDARY Number of Participants With Response in PGI-I |
45; 102; 113; 260 | — |
| SECONDARY Number of Participants With Response in PGI-I for Early Morning Off Symptoms |
45; 103; 112; 260 | — |
| SECONDARY UPDRS I Total Score and Change From OL Baseline at Week 80 |
0.1; 0.5; 0.5 | 0.0831 |
| SECONDARY UPDRS II Total Score and Change From OL Baseline at Week 80 |
-0.4; 0.4; 1.0 | 0.1713 |
| SECONDARY UPDRS III Total Score and Change From OL Baseline at Week 80 |
-3.1; 0.7; 1.3 | 0.0015 sig |
| SECONDARY UPDRS IV Total Score and Change From OL Baseline at Week 80 |
0.0; -0.0; 0.2 | 0.8760 |
| SECONDARY Parkinson Fatigue Scale (PFS-16) Score and Change From OL Baseline at Week 80 |
-0.3; 3.8; 3.5 | 0.0148 sig |
| SECONDARY Number of Participants With L-dopa Daily Dose Change: Change From OL Baseline at Week 80 |
24; 12; 12; 48; 8; 18 | — |
| SECONDARY Number of Participants With Changes in Pramipexole Doses After 80 Weeks Compared to Pramipexole Dose at OL Baseline |
56; 33; 26; 115; 40; 43 | — |
| SECONDARY Number of Participants With Serious Adverse Events |
14; 11; 14; 39 | — |
| SECONDARY Supine Diastolic Blood Pressure, Baseline and Week 80, Vital Signs Treated Set |
77.4; 77.3; 77.6; 77.4; 78.3; 77.2 | — |
| SECONDARY Standing Diastolic Blood Pressure, Baseline and Week 80, Vital Signs Treated Set |
77.8; 77.3; 77.6; 77.6; 78.1; 76.4 | — |
| SECONDARY Supine Systolic Blood Pressure, Baseline and Week 80, Vital Signs Treated Set |
121.6; 124.5; 125.7; 124.2; 123.8; 124.4 | — |
| SECONDARY Standing Systolic Blood Pressure, Baseline and Week 80, Vital Signs Treated Set |
120.2; 121.1; 120.9; 121.9; 121.6; 120.5 | — |
| SECONDARY Supine Pulse Rate, Baseline and Week 80, Vital Signs Treated Set |
73.6; 72.6; 73.2; 75.8; 74.2; 74.4 | — |
| SECONDARY Standing Pulse Rate, Baseline and Week 80, Vital Signs Treated Set |
78.3; 78.0; 77.7; 79.3; 77.7; 78.8 | — |
| SECONDARY Body Weight of Female Patients, Baseline and Week 80, Vital Signs Treated Set |
61.9; 61.7; 63.8; 63.6; 61.7; 63.6 | — |
| SECONDARY Body Weight of Male Patients, Baseline and Week 80, Vital Signs Treated Set |
73.0; 72.1; 70.8; 73.9; 72.7; 72.0 | — |
| SECONDARY Epworth Sleepiness Scale (ESS), Baseline and End of Open Label, Treated Set |
7.2; 8.1; 8.1; 0.5; 1.2; 1.2 | — |
| SECONDARY Modified Minnesota Impulsive Disorder Interview (mMIDI), Frequency of Patients With at Least One Abnormal Behavior, Treated Set |
0; 0; 0; 2; 0; 2 | — |
Eligibility Criteria
Inclusion criteria
- Completion of the double-blind trial 248.525
- Male or female patient with advanced idiopathic Parkinson's disease (PD), with a Modified Hoehn and Yahr stage of 2 to 4 at on-time, and a concomitant treatment with standard or controlled release L-Dopa+, or a combination of L-Dopa+ and entacapone.
- Patient willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. In particular the patient should be able to recognise the off-time and on-time periods during waking hours and the patient (or a family member or a guardian) should be 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 of Harmonization - Good Clinical Practice (ICH-GCP) guidelines and local legislation).
Exclusion criteria
- Patients prematurely withdrawn from the double-blind trial 248.525
- Atypical parkinsonian syndromes due to drugs, metabolic disorders, encephalitis or degenerative diseases
- Any psychiatric disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV 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
- History of psychosis, except history of drug induced hallucinations
- History of deep brain stimulation
- Clinically significant ECG abnormalities at baseline
- Clinically significant hypotension and/or symptomatic orthostatic hypotension at baseline
- Malignant melanoma or history of previously treated malignant melanoma
- 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
- Pregnancy or breast-feeding
- Sexually active female of childbearing potential not using a medically approved method of birth control
- Serum levels of aspartate transaminase (AST) (serum glutamic oxaloacetic transaminase (SGOT)), alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase) (SGPT)), alkaline phosphatase (AP) or bilirubin > 2 upper limit normal (ULN) at baseline
- Patients with a creatinine clearance < 50 mL/min at baseline
- 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
- Known hypersensitivity to pramipexole or its excipients
- Drug abuse, according to investigators judgement, within 2 years prior to baseline
- Participation in investigational drug studies other than the trial 248.525, 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
Data sourced from ClinicalTrials.gov (NCT00577460). 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.