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

Long-term Safety Study of Open-label Pramipexole Extended Release (ER) in Patients With Advanced Parkinson's Disease (PD)

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 Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Pramipexole; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 391
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria
    • 248.634.43005 Boehringer Ingelheim Investigational Site
• Czech Republic
  • Pardubice, Czech Republic
    • 248.634.42003 Boehringer Ingelheim Investigational Site
  • Praha, Czech Republic
    • 248.634.42001 Boehringer Ingelheim Investigational Site
  • Rakovnik, Czech Republic
    • 248.634.42005 Boehringer Ingelheim Investigational Site
  • Rychnov nad Kneznou, Czech Republic
    • 248.634.42002 Boehringer Ingelheim Investigational Site
  • Valasske Mezirici, Czech Republic
    • 248.634.42004 Boehringer Ingelheim Investigational Site
• Hungary
  • Györ, Hungary
    • 248.634.36005 Boehringer Ingelheim Investigational Site
  • Kecskemét, Hungary
    • 248.634.36003 Boehringer Ingelheim Investigational Site
  • Szeged, Hungary
    • 248.634.36006 Boehringer Ingelheim Investigational Site
  • Veszprem, Hungary
    • 248.634.36004 Boehringer Ingelheim Investigational Site
• India
  • Chennai, India
    • 248.634.91002 Boehringer Ingelheim Investigational Site
  • Delhi, India
    • 248.634.91001 Boehringer Ingelheim Investigational Site
  • Hyderabad, India
    • 248.634.91003 Boehringer Ingelheim Investigational Site
  • Indore, India
    • 248.634.91007 Boehringer Ingelheim Investigational Site
  • Karnataka, India
    • 248.634.91005 Boehringer Ingelheim Investigational Site
  • Pune, India
    • 248.634.91006 Boehringer Ingelheim Investigational Site
• Italy
  • Catania, Italy
    • 248.634.39001 Boehringer Ingelheim Investigational Site
  • Catanzaro, Italy
    • 248.634.39010 Boehringer Ingelheim Investigational Site
  • Chieti, Italy
    • 248.634.39009 Boehringer Ingelheim Investigational Site
  • Grosseto, Italy
    • 248.634.39007 Boehringer Ingelheim Investigational Site
  • Napolii, Italy
    • 248.634.39002 Boehringer Ingelheim Investigational Site
  • Pisa, Italy
    • 248.634.39008 Boehringer Ingelheim Investigational Site
  • Roma, Italy
    • 248.634.39005 Boehringer Ingelheim Investigational Site
  • Roma, Italy
    • 248.634.39011 Boehringer Ingelheim Investigational Site
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of
    • 248.634.82001 Boehringer Ingelheim Investigational Site
  • Kyeonggi-do, Korea, Republic of
    • 248.634.82008 Boehringer Ingelheim Investigational Site
  • Pusan, Korea, Republic of
    • 248.634.82007 Boehringer Ingelheim Investigational Site
  • Seoul, Korea, Republic of
    • 248.634.82002 Boehringer Ingelheim Investigational Site
  • Seoul, Korea, Republic of
    • 248.634.82003 Boehringer Ingelheim Investigational Site
  • Seoul, Korea, Republic of
    • 248.634.82004 Boehringer Ingelheim Investigational Site
  • Seoul, Korea, Republic of
    • 248.634.82005 Boehringer Ingelheim Investigational Site
  • Seoul, Korea, Republic of
    • 248.634.82006 Boehringer Ingelheim Investigational Site
• Philippines
  • Cruz, Manila, Philippines
    • 248.634.63202 Boehringer Ingelheim Investigational Site
  • Ermita, Manila, Philippines
    • 248.634.63207 Boehringer Ingelheim Investigational Site
  • Makati City, Philippines
    • 248.634.63210 Boehringer Ingelheim Investigational Site
  • Manila, Philippines
    • 248.634.63205 Boehringer Ingelheim Investigational Site
  • Manila, Philippines
    • 248.634.63206 Boehringer Ingelheim Investigational Site
  • Pasig City, Philippines
    • 248.634.63201 Boehringer Ingelheim Investigational Site
  • Quezon, Philippines
    • 248.634.63208 Boehringer Ingelheim Investigational Site
  • Quezon City, Philippines
    • 248.634.63204 Boehringer Ingelheim Investigational Site
• Poland
  • Gdansk, Poland
    • 248.634.48001 Boehringer Ingelheim Investigational Site
  • Krakow, Poland
    • 248.634.48003 Boehringer Ingelheim Investigational Site
  • Warsaw, Poland
    • 248.634.48002 Boehringer Ingelheim Investigational Site
• Russian Federation
  • Moscow, Russian Federation
    • 248.634.07001 Boehringer Ingelheim Investigational Site
  • Moscow, Russian Federation
    • 248.634.07002 Boehringer Ingelheim Investigational Site
  • Moscow, Russian Federation
    • 248.634.07003 Boehringer Ingelheim Investigational Site
  • Moscow, Russian Federation
    • 248.634.07004 Boehringer Ingelheim Investigational Site
  • Moscow, Russian Federation
    • 248.634.07007 Boehringer Ingelheim Investigational Site
  • St. Petersburg, Russian Federation
    • 248.634.07006 Boehringer Ingelheim Investigational Site
• Slovakia
  • Bratislava, Slovakia
    • 248.634.42104 Boehringer Ingelheim Investigational Site
  • Bratislava, Slovakia
    • 248.634.42105 Boehringer Ingelheim Investigational Site
  • Dubnica nad Vahom, Slovakia
    • 248.634.42103 Boehringer Ingelheim Investigational Site
  • Trnava, Slovakia
    • 248.634.42101 Boehringer Ingelheim Investigational Site
• Spain
  • Alcorcon (Madrid), Spain
    • 248.634.34001 Boehringer Ingelheim Investigational Site
  • Barcelona, Spain
    • 248.634.34003 Boehringer Ingelheim Investigational Site
  • Barcelona, Spain
    • 248.634.34004 Boehringer Ingelheim Investigational Site
  • Madrid, Spain
    • 248.634.34005 Boehringer Ingelheim Investigational Site
  • San Cugat del Valles (Barcelona), Spain
    • 248.634.34002 Boehringer Ingelheim Investigational Site
  • Tarrasa (Barcelona), Spain
    • 248.634.34008 Boehringer Ingelheim Investigational Site
• Sweden
  • Malmö, Sweden
    • 248.634.46005 Boehringer Ingelheim Investigational Site
  • Nyköping, Sweden
    • 248.634.46002 Boehringer Ingelheim Investigational Site
  • Stockholm, Sweden
    • 248.634.46001 Boehringer Ingelheim Investigational Site
• Ukraine
  • Dnipropetrovsk, Ukraine
    • 248.634.38003 Boehringer Ingelheim Investigational Site
  • Kharkiv, Ukraine
    • 248.634.38006 Boehringer Ingelheim Investigational Site
  • Kiev, Ukraine
    • 248.634.38002 Boehringer Ingelheim Investigational Site
  • Kiev, Ukraine
    • 248.634.38004 Boehringer Ingelheim Investigational Site
  • Zaporizhzhya, Ukraine
    • 248.634.38005 Boehringer Ingelheim Investigational Site
  • Zaporozhye, Ukraine
    • 248.634.38001 Boehringer Ingelheim Investigational Site
• United Kingdom
  • Blackburn, United Kingdom
    • 248.634.44007 Boehringer Ingelheim Investigational Site
  • Salford, United Kingdom
    • 248.634.44003 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 32 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Pramipexole; Patients to receive Pramipexole ER 0.375 - 4.5 mg in tablet form daily	Drug: Pramipexole; Pramipexole ER 0.375 -4.5 mg
PLACEBO_COMPARATOR: Placebo; Patients to receive placebo tablets identical to Pramipexole ER tablets only during transfer phase	Drug: Placebo; Placebo tablets identical to Pramipexole ER tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	80 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	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).	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	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	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.	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	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	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	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	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	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	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	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	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	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	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	OL baseline and week 80
Number of Participants With L-dopa Daily Dose Change: Change From OL Baseline at Week 80		OL baseline and week 80
Number of Participants With Changes in Pramipexole Doses After 80 Weeks Compared to Pramipexole Dose at OL Baseline		OL baseline and week 80
Number of Participants With Serious Adverse Events		80 weeks
Supine Diastolic Blood Pressure, Baseline and Week 80, Vital Signs Treated Set		OL Baseline and Week 80
Standing Diastolic Blood Pressure, Baseline and Week 80, Vital Signs Treated Set		OL Baseline and Week 80
Supine Systolic Blood Pressure, Baseline and Week 80, Vital Signs Treated Set		OL Baseline and Week 80
Standing Systolic Blood Pressure, Baseline and Week 80, Vital Signs Treated Set		OL Baseline and Week 80
Supine Pulse Rate, Baseline and Week 80, Vital Signs Treated Set		OL Baseline and Week 80
Standing Pulse Rate, Baseline and Week 80, Vital Signs Treated Set		OL Baseline and Week 80
Body Weight of Female Patients, Baseline and Week 80, Vital Signs Treated Set		OL Baseline and Week 80
Body Weight of Male Patients, Baseline and Week 80, Vital Signs Treated Set		OL Baseline and Week 80
Epworth Sleepiness Scale (ESS), Baseline and End of Open Label, Treated Set	ESS Total score ranges from zero (best) to 24 (worst); scale has 8 items, each rated from zero (no chance of dozing) to 3 (high chance of dozing)	OL Baseline and Week 80
Modified Minnesota Impulsive Disorder Interview (mMIDI), Frequency of Patients With at Least One Abnormal Behavior, Treated Set	The mMIDI is a semi-structured interview designed to assess impulsive control disorders. The scale was modified to focus behaviors of: pathological gambling, compulsive buying and compulsive sexual behavioral.	Baseline, 80 weeks

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (ACTUAL): June 1, 2010

Study Registration Dates

• First Submitted: December 19, 2007
• First Submitted That Met QC Criteria: December 19, 2007
• First Posted (ESTIMATE): December 20, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): May 16, 2014
• Last Update Submitted That Met QC Criteria: May 7, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; Dopamine Agonists; Dopamine Agents; Antioxidants; Antiparkinson Agents; Anti-Dyskinesia Agents; Pramipexole
• Other Study ID Numbers: 248.634; 2007-004235-37 (EUDRACT_NUMBER: EudraCT)