Long-term Safety Study of Open-label Pramipexole ER in Patients With Advanced PD

Boehringer Ingelheim391 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

391

Conditions

Parkinson Disease

Interventions

PramipexoleDRUG

Pramipexole ER 0.375 -4.5 mg

PlaceboDRUG

Placebo tablets identical to Pramipexole ER tablets

Eligibility

Sex: ALLMin age: 32 Years

Medical Language ↔ Plain English

Inclusion criteria: 1. Completion of the double-blind trial 248.525 2. 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. 3. 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. 4. 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: 1. Patients prematurely withdrawn from the double-blind trial 248.525 2. Atypical parkinsonian syndromes due to drugs, metabolic disorders, encephalitis or degenerative diseases 3. 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 4. History of psychosis, except history of drug induced hallucinations 5. History of deep brain stimulation 6. Clinically significant ECG abnormalities at baseline 7. Clinically significant hypotension and/or symptomatic orthostatic hypotension at baseline 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 12. 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 13. Patients with a creatinine clearance \< 50 mL/min at baseline 14. Any medication with central dopaminergic antagonist activity within 4 weeks prior to the baseline visit 15. Any of the following drugs within 4 weeks prior to baseline visit: methylphenidate, cinnarizine, amphetamines 16. Flunarizine within 3 months prior to baseline 17. Known hypersensitivity to pramipexole or its excipients 18. Drug abuse, according to investigators judgement, within 2 years prior to baseline 19. 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

Locations (70)

Outcomes

Primary Outcomes

Percentage of Patients With Adverse Events, Adverse Drug Reactions, Serious Adverse Events

The aim of this study was to obtain long-term safety and tolerability data on pramipexole ER, in patients who have previously completed a pramipexole double blind study in advanced Parkinson's Disease (PD) (248.525 (NCT00466167)). Therefore these items were considered as a safety evaluation.

Time frame: 80 weeks

Secondary Outcomes

Patients Successfully Switched From Pramipexole (PPX) IR or ER to ER Assessed on UPDRS II+III

Unified Parkinson's Disease Rating Scale (UPDRS) Successfully switched means: UPDRS II+III baseline score \>20 without a relative worsening of UPDRS II+III score \> 15% from baseline or UPDRS II+III baseline score \<=20 without an absolute worsening of UPDRS II+III score \> 3 from 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: One week

UPDRS II+III Change From Open Label (OL) 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: OL Baseline and week 80

Number of Participants With UPDRS II+III Response

A response means an improvement of \>=20% in UPDRS II+III from OL 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: Week 80

Number of Patients Successfully Switched From PPX IR or ER to ER Assessed on Off-time

A patient was considered as successfully switched if he/she has converted to ER without a worsening of off time by more than 12.5% from baseline. Off-time is based on patient diary data and describes a period when the patient experiences increased parkinsonian symptoms (e.g. immobility or inability to move with ease).

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

248.634.43005 Boehringer Ingelheim Investigational Site

Linz, Austria

248.634.42003 Boehringer Ingelheim Investigational Site

Pardubice, Czechia

248.634.42001 Boehringer Ingelheim Investigational Site

Prague, Czechia

248.634.42005 Boehringer Ingelheim Investigational Site

Rakovník, Czechia

248.634.42002 Boehringer Ingelheim Investigational Site

Rychnov nad Kněžnou, Czechia

248.634.42004 Boehringer Ingelheim Investigational Site

Valašské Meziříčí, Czechia

248.634.36005 Boehringer Ingelheim Investigational Site

Győr, Hungary

248.634.36003 Boehringer Ingelheim Investigational Site

Kecskemét, Hungary

248.634.36006 Boehringer Ingelheim Investigational Site

Szeged, Hungary

248.634.36004 Boehringer Ingelheim Investigational Site

Veszprém, Hungary

...and 60 more locations

Time frame: One week

Percentage Off Time During Waking Hours Total Score: Change From Baseline

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). A negative change implies improvement

Time frame: Baseline and week 80

Number of Participants With Response in Percentage Off Time During Waking Hours

Response means \>=20% improvement relative to OL baseline in the % off-time during waking hours

Time frame: 80 weeks

Percentage on Time Without Dyskinesia During Waking Hours: Change From Baseline After 80 Weeks

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. A positive change implies improvement.

Time frame: Baseline and week 80

Percentage on Time With Non Troublesome Dyskinesia During Waking Hours: Change From Baseline After 80 Weeks

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. A positive change implies improvement

Time frame: Baseline and week 80

Percentage on Time Without Dyskinesia or With Non Troublesome Dyskinesia During Waking Hours: Change From Baseline After 80 Weeks

Percentage on-time without dyskinesia or 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. A positive change implies improvement

Time frame: Baseline and week 80

Percentage on Time With Troublesome Dyskinesia During Waking Hours: Change From Baseline After 80 Weeks

Percentage on-time with 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. A positive change implies improvement

Time frame: Baseline and week 80

Number of Participants With Response in CGI-I

Clinical Global Impression of Improvement (CGI-I), CGI-I scores ranging from '1' (very much improved) to '7' (very much worse). For patients previously treated with Placebo, all patients with at least "much improved" were considered as responders. For patients previously treated with PPX ER or IR, all patients with no change to very much improved were considered as responders

Time frame: 32 weeks

Number of Participants With Response in PGI-I

Patient Global Impression of Improvement (PGI-I), PGI-I scores ranging from '1' (very much better) to '7' (very much worse). For patients previously treated with Placebo, all patients with at least "much better" were considered as responders. For patients previously treated with PPX ER or IR, all patients with no change to very much better were considered as responders

Time frame: 32 weeks

Number of Participants With Response in PGI-I for Early Morning Off Symptoms

Patient Global Impression of Improvement (PGI-I) for early morning off symptoms, PGI-I scores ranging from '1' (very much better) to '7' (very much worse). For patients previously treated with Placebo, all patients with at least "much better" were considered as responders. For patients previously treated with PPX ER or IR, all patients with no change to very much better were considered as responders

Time frame: 32 weeks

UPDRS I Total Score and Change From OL Baseline at Week 80

UPDRS I ranging from 0 (normal) to 16 (severe). UPDRS I measures Mentation, Behavior and Mood

Time frame: OL baseline and week 80

UPDRS II Total Score and Change From OL Baseline at Week 80

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: OL baseline and week 80

UPDRS III Total Score and Change From OL Baseline at Week 80

UPDRS III ranging from 0 (normal) to 108 (severe). UPDRS part III measures motor symptoms

Time frame: OL baseline and week 80

UPDRS IV Total Score and Change From OL Baseline at Week 80

UPDRS IV ranging from 0 (normal) to 23 (severe). UPDRS IV measures complications of therapy

Time frame: OL baseline and week 80

Parkinson Fatigue Scale (PFS-16) Score and Change From OL Baseline at Week 80

PFS-16 (Parkinson fatigue scale) ranging from 16 (better perceived health status) to 80 (severe symptoms of the disease) measuring aspects of fatigue that are relevant to patients with PD

Time frame: OL baseline and week 80

Number of Participants With L-dopa Daily Dose Change: Change From OL Baseline at Week 80

Time frame: OL baseline and week 80

Number of Participants With Changes in Pramipexole Doses After 80 Weeks Compared to Pramipexole Dose at OL Baseline

Time frame: OL baseline and week 80

Number of Participants With Serious Adverse Events

Time frame: 80 weeks

Supine Diastolic Blood Pressure, Baseline and Week 80, Vital Signs Treated Set