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

The general aim of this study is to obtain long-term safety and tolerability data on pramipexole ER, in daily doses from 0.375mg to 4.5mg once daily (q.d), in patients who have previously completed a pramipexole double-blind study in early PD (248.524(NCT00479401) or 248.636(NCT00558025) trial).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 511
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria
    • 248.633.43001 Boehringer Ingelheim Investigational Site
  • Wien, Austria
    • 248.633.43004 Boehringer Ingelheim Investigational Site
• Czech Republic
  • Olomouc, Czech Republic
    • 248.633.42004 Boehringer Ingelheim Investigational Site
  • Pardubice, Czech Republic
    • 248.633.42003 Boehringer Ingelheim Investigational Site
  • Praha, Czech Republic
    • 248.633.42001 Boehringer Ingelheim Investigational Site
  • Rychnov nad Kneznou, Czech Republic
    • 248.633.42002 Boehringer Ingelheim Investigational Site
• Finland
  • Hyvinkää, Finland
    • 248.633.35803 Boehringer Ingelheim Investigational Site
  • Oulu, Finland
    • 248.633.35801 Boehringer Ingelheim Investigational Site
  • Tampere, Finland
    • 248.633.35802 Boehringer Ingelheim Investigational Site
• France
  • Aix en Provence, France
    • 248.633.3303A Boehringer Ingelheim Investigational Site
  • Aix en Provence, France
    • 248.633.3303B Boehringer Ingelheim Investigational Site
  • Aix en Provence, France
    • 248.633.3303C Boehringer Ingelheim Investigational Site
  • Clermont Ferrand, France
    • 248.633.3309A Boehringer Ingelheim Investigational Site
  • Clermont Ferrand, France
    • 248.633.3309B Boehringer Ingelheim Investigational Site
  • Créteil, France
    • 248.633.3305A Boehringer Ingelheim Investigational Site
  • Créteil, France
    • 248.633.3305B Boehringer Ingelheim Investigational Site
  • Dijon cedex, France
    • 248.633.3313A Boehringer Ingelheim Investigational Site
  • Evreux, France
    • 248.633.3304A Boehringer Ingelheim Investigational Site
  • Lille cedex, France
    • 248.633.3308A Boehringer Ingelheim Investigational Site
  • Lille cedex, France
    • 248.633.3308B Boehringer Ingelheim Investigational Site
  • Lille cedex, France
    • 248.633.3308C Boehringer Ingelheim Investigational Site
  • Lille cedex, France
    • 248.633.3308D Boehringer Ingelheim Investigational Site
  • Lille cedex, France
    • 248.633.3308E Boehringer Ingelheim Investigational Site
  • Marseille cedex 5, France
    • 248.633.3302A Boehringer Ingelheim Investigational Site
  • Marseille cedex 5, France
    • 248.633.3302B Boehringer Ingelheim Investigational Site
  • Marseille cedex 5, France
    • 248.633.3302C Boehringer Ingelheim Investigational Site
  • Montpellier, France
    • 248.633.3306B Boehringer Ingelheim Investigational Site
  • Montpellier, France
    • 248.633.3306C Boehringer Ingelheim Investigational Site
  • Montpellier, France
    • 248.633.3306D Boehringer Ingelheim Investigational Site
  • Montpellier, France
    • 248.633.3306F Boehringer Ingelheim Investigational Site
  • Montpellier cédex 5, France
    • 248.633.3306A Boehringer Ingelheim Investigational Site
  • Rouen, France
    • 248.633.3312A Boehringer Ingelheim Investigational Site
  • Rouen, France
    • 248.633.3312B Boehringer Ingelheim Investigational Site
  • Strasbourg, France
    • 248.633.3311A Boehringer Ingelheim Investigational Site
  • Strasbourg, France
    • 248.633.3311B Boehringer Ingelheim Investigational Site
  • Toulouse, France
    • 248.633.3301A Boehringer Ingelheim Investigational Site
  • Toulouse, France
    • 248.633.3301D Boehringer Ingelheim Investigational Site
  • Toulouse, France
    • 248.633.3301F Boehringer Ingelheim Investigational Site
  • Toulouse, France
    • 248.633.3301G Boehringer Ingelheim Investigational Site
  • Toulouse Cedex 7, France
    • 248.633.3301C Boehringer Ingelheim Investigational Site
  • Toulouse cedex, France
    • 248.633.3301B Boehringer Ingelheim Investigational Site
• Germany
  • Achim bei Bremen, Germany
    • 248.633.49009 Boehringer Ingelheim Investigational Site
  • Berlin, Germany
    • 248.633.49002 Boehringer Ingelheim Investigational Site
  • Berlin, Germany
    • 248.633.49004 Boehringer Ingelheim Investigational Site
  • Berlin, Germany
    • 248.633.49018 Boehringer Ingelheim Investigational Site
  • Berlin, Germany
    • 248.633.49019 Boehringer Ingelheim Investigational Site
  • Berlin-Steglitz, Germany
    • 248.633.49003 Boehringer Ingelheim Investigational Site
  • Bochum, Germany
    • 248.633.49005 Boehringer Ingelheim Investigational Site
  • Bochum, Germany
    • 248.633.49016 Boehringer Ingelheim Investigational Site
  • Dresden, Germany
    • 248.633.49007 Boehringer Ingelheim Investigational Site
  • Gera, Germany
    • 248.633.49011 Boehringer Ingelheim Investigational Site
  • Karlsruhe, Germany
    • 248.633.49017 Boehringer Ingelheim Investigational Site
  • Kassel, Germany
    • 248.633.49001 Boehringer Ingelheim Investigational Site
  • Leipzig, Germany
    • 248.633.49012 Boehringer Ingelheim Investigational Site
  • Marburg, Germany
    • 248.633.49013 Boehringer Ingelheim Investigational Site
  • Unterhaching, Germany
    • 248.633.49015 Boehringer Ingelheim Investigational Site
• Hungary
  • Eger, Hungary
    • 248.633.36007 Boehringer Ingelheim Investigational Site
  • Györ, Hungary
    • 248.633.36005 Boehringer Ingelheim Investigational Site
  • Miskolc, Hungary
    • 248.633.36008 Boehringer Ingelheim Investigational Site
  • Sopron, Hungary
    • 248.633.36004 Boehringer Ingelheim Investigational Site
  • Szeged, Hungary
    • 248.633.36001 Boehringer Ingelheim Investigational Site
  • Szeged, Hungary
    • 248.633.36006 Boehringer Ingelheim Investigational Site
  • Szombathely, Hungary
    • 248.633.36003 Boehringer Ingelheim Investigational Site
  • Zalaegerszeg, Hungary
    • 248.633.36002 Boehringer Ingelheim Investigational Site
• India
  • Chennai, India
    • 248.633.91002 Boehringer Ingelheim Investigational Site
  • Hyderabad, India
    • 248.633.91009 Boehringer Ingelheim Investigational Site
  • Karnataka, India
    • 248.633.91001 Boehringer Ingelheim Investigational Site
  • Maharashtra, India
    • 248.633.91005 Boehringer Ingelheim Investigational Site
  • Maharashtra, India
    • 248.633.91007 Boehringer Ingelheim Investigational Site
  • New Delhi, India
    • 248.633.91004 Boehringer Ingelheim Investigational Site
  • Pune, India
    • 248.633.91011 Boehringer Ingelheim Investigational Site
• Japan
  • Aomori, Aomori, Japan
    • 248.633.81010 Boehringer Ingelheim Investigational Site
  • Bunkyo-ku, Tokyo, Japan
    • 248.633.81001 Boehringer Ingelheim Investigational Site
  • Fuchu, Tokyo, Japan
    • 248.633.81005 Boehringer Ingelheim Investigational Site
  • Fujisawa, Kanagawa, Japan
    • 248.633.81011 Boehringer Ingelheim Investigational Site
  • Fukuoka, Fukuoka, Japan
    • 248.633.81013 Boehringer Ingelheim Investigational Site
  • Iwamizawa,Hokkaido, Japan
    • 248.633.81015 Boehringer Ingelheim Investigational Site
  • Kodaira, Tokyo, Japan
    • 248.633.81003 Boehringer Ingelheim Investigational Site
  • Kyoto, Kyoto, Japan
    • 248.633.81014 Boehringer Ingelheim Investigational Site
  • Morioka, Iwate, Japan
    • 248.633.81009 Boehringer Ingelheim Investigational Site
  • Okayama, Okayama, Japan
    • 248.633.81008 Boehringer Ingelheim Investigational Site
  • Ota-ku, Tokyo, Japan
    • 248.633.81006 Boehringer Ingelheim Investigational Site
  • Sagamihara, Kanagawa, Japan
    • 248.633.81004 Boehringer Ingelheim Investigational Site
  • Shimogyo-ku, Kyoto, Kyoto, Japan
    • 248.633.81007 Boehringer Ingelheim Investigational Site
  • Shiroishi, Miyagi, Japan
    • 248.633.81012 Boehringer Ingelheim Investigational Site
  • Takamatsu, Kagawa, Japan
    • 248.633.81002 Boehringer Ingelheim Investigational Site
• Malaysia
  • Kuala Terengganu, Malaysia
    • 248.633.60004 Boehringer Ingelheim Investigational Site
• Netherlands
  • Geldrop, Netherlands
    • 248.633.31002 Boehringer Ingelheim Investigational Site
  • Helmond, Netherlands
    • 248.633.31003 Boehringer Ingelheim Investigational Site
  • Maastricht, Netherlands
    • 248.633.31006 Boehringer Ingelheim Investigational Site
  • Nijmegen, Netherlands
    • 248.633.31004 Boehringer Ingelheim Investigational Site
  • Sittard-geleen, Netherlands
    • 248.633.31001 Boehringer Ingelheim Investigational Site
• Russian Federation
  • Moscow, Russian Federation
    • 248.633.07001 Boehringer Ingelheim Investigational Site
  • Moscow, Russian Federation
    • 248.633.07002 Boehringer Ingelheim Investigational Site
  • Moscow, Russian Federation
    • 248.633.07003 Boehringer Ingelheim Investigational Site
  • Moscow, Russian Federation
    • 248.633.07004 Boehringer Ingelheim Investigational Site
  • St. Petersburg, Russian Federation
    • 248.633.07006 Boehringer Ingelheim Investigational Site
• Slovakia
  • Dubnica nad Vahom, Slovakia
    • 248.633.42103 Boehringer Ingelheim Investigational Site
  • Trnava, Slovakia
    • 248.633.42101 Boehringer Ingelheim Investigational Site
• Taiwan
  • Kaohsiung, Taiwan
    • 248.633.88603 Boehringer Ingelheim Investigational Site
  • Taichung, Taiwan
    • 248.633.88605 Boehringer Ingelheim Investigational Site
  • Taipei, Taiwan
    • 248.633.88601 Boehringer Ingelheim Investigational Site
  • Taoyuan, Taiwan
    • 248.633.88602 Boehringer Ingelheim Investigational Site
• Ukraine
  • Kiev, Ukraine
    • 248.633.38005 Boehringer Ingelheim Investigational Site
  • Lvov, Ukraine
    • 248.633.38001 Boehringer Ingelheim Investigational Site
  • Uzhgorod, Ukraine
    • 248.633.38002 Boehringer Ingelheim Investigational Site
  • Vinnytzya, Ukraine
    • 248.633.38003 Boehringer Ingelheim Investigational Site
  • Zaporizhzhya, Ukraine
    • 248.633.38004 Boehringer Ingelheim Investigational Site
  • Zaporozhye, Ukraine
    • 248.633.38006 Boehringer Ingelheim Investigational Site
• United States
  • Arizona
    • Sun City, Arizona, United States
      • 248.633.01004 Boehringer Ingelheim Investigational Site
    • Tempe, Arizona, United States
      • 248.633.01018 Boehringer Ingelheim Investigational Site
  • California
    • La Jolla, California, United States
      • 248.633.01016 Boehringer Ingelheim Investigational Site
    • Oxnard, California, United States
      • 248.633.01013 Boehringer Ingelheim Investigational Site
  • Connecticut
    • Danbury, Connecticut, United States
      • 248.633.01008 Boehringer Ingelheim Investigational Site
  • Florida
    • Boca Raton, Florida, United States
      • 248.633.01010 Boehringer Ingelheim Investigational Site
  • Illinois
    • Chicago, Illinois, United States
      • 248.633.01012 Boehringer Ingelheim Investigational Site
  • Kansas
    • Kansas City, Kansas, United States
      • 248.633.01001 Boehringer Ingelheim Investigational Site
  • New York
    • Commack, New York, United States
      • 248.633.01005 Boehringer Ingelheim Investigational Site
  • Vermont
    • Burlington, Vermont, United States
      • 248.633.01009 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 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 248.524 or 248.636
2. Male or female patient with early idiopathic Parkinson´s disease (PD), and with a Modified Hoehn and Yahr stage of I to III.
3. Patient willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
4. Signed informed consent obtained before any study procedures are carried out (in accordance with International Conference on Harmonisation (ICH) - Good Clinical Practice (GCP) guidelines and local legislation).

Exclusion criteria:

1. Patients prematurely withdrawn from the double-blind trials 248.524 or 248.636.
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, fourth edition (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. Clinically significant electrocardiogram (ECG) abnormalities at baseline. 6.Clinically significant hypotension 7.Malignant melanoma or history of previously treated malignant melanoma. 8.Any other clinically significant disease, that could put the patient at risk or could prevent compliance or completion of the study. 9. Pregnancy or breast-feeding.

10. Sexually active female of childbearing potential not using a medically approved method of birth control for at least one month prior to the baseline and throughout the study.11 Serum levels of aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT), alkaline phosphatase or bilirubin > 2 upper limit of normal (ULN) at baseline 12. Patients with a creatinine clearance < 50 mL/min (estimated by the Cockcroft and Gault formula). 13. Motor complications under levodopa therapy (e.g. on-off phenomena, dyskinesia) at baseline.

14. Any medication (including intra-muscular formulations) 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: methylphenidate, cinnarizine, amphetamines. 16. Flunarizine within 3 months prior to baseline.

17. Known hypersensitivity to pramipexole or its excipients. 18. Drug abuse (including alcohol), according to investigator´s judgement, within 2 years prior to baseline.

19. Participation in investigational drug studies other than trials 248.524 and 248.636 or use of other investigational drug within one month or five times the half-life of the investigational drug prior to baseline.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pramipexole; Patient to receive Pramipexole ER 0.375-4.5 mg tabl form daily	Drug: Pramipexole; ER 0.375-4,5 mg
Placebo Comparator: Placebo; Patient to receive placebo tablets identical to Pramipexole ER tablets. Only during transfer phase.	Drug: Placebo; Patient to receive placebo tablets identical to Pramipexole ER tablets. Only during transfer phase.

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 early PD (248.524 (NCT00479401) or 248.636 (NCT00558025)). Therefore these items were considered as a safety evaluation	80 weeks (patients from 248.524) or 72 weeks (patients from 248.636)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Unified Parkinson's Disease Rating Scale (UPDRS) II+III Total Score: Change 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	Open Label (OL) baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636)
Number of Patients With UPDRS II+III Response From OL Baseline at Week 80 (Patients From 248.524) or Week 72 (Patients From 248.636)	A response means an improvement of >=20% 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	OL Baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636)
UPDRS I Total Score: Change From OL Baseline	UPDRS I ranging from 0 (normal) to 16 (severe), measures Mentation, Behavior and Mood	OL baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636)
UPDRS II Total Score: Change From OL Baseline	UPDRS II ranging from 0 (normal) to 52 (severe), measures activity of daily living.	OL baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636)
UPDRS III Total Score: Change From OL Baseline	UPDRS III ranging from 0 (normal) to 108 (severe) measures motor symptoms	OL baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636)
Response in Clinical Global Impression of Improvement (CGI-I)	Clinicians evaluation in a rating scale of 7 steps, 1 meaning very much improved to 7 meaning 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 Pramipexole ER or Immediate Release (IR), all patients with no change to very much improved were considered as responders	OL Baseline and week 32 (patients from 248.524) or week 24 (patients from 248.636)
Response in Patient Global Impression of Improvement (PGI-I)	Patient rated evaluation of the PD symptoms on a rating scale of 7 steps, 1 meaning very much better to 7 meaning 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 pramipexole (PPX) ER or IR, all patients with no change to very much better were considered as responders	OL Baseline and week 32 (patients from 248.524) or week 24 (patients from 248.636)
Parkinson Fatigue Scale (PFS-16) : Change From OL Baseline	PFS-16 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 (patients from 248.524) or week 72 (patients from 248.636)
Number of Patients Introducing L-Dopa Medication in OL Trial	Number of patients requiring Levodopa supplementation during the study	80 weeks (patients from 248.524) or 72 weeks (patients from 248.636)
L-Dopa Dose: Change From OL Baseline	Change from open-label baseline in Levodopa dose	OL baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636)
Pramipexole Doses Respectively After 80 Weeks Compared to Pramipexole Doses at Week 8 for Previously 248.524 Patients and After 72 Weeks Compared to Pramipexole Doses at Week 0 for Previously 248.636 Patients	Change from open-label baseline in Levodopa dose over the final 72 weeks of open-label assessment	Week 8 and week 80 (patients from 248.524) or week 0 and week 72 (patients from 248.636)
Patient Preference Regarding Treatment Dosing	Patients were surveyed on their preference for Once Daily dosing versus Three Times Daily dosing	80 weeks (patients from 248.524) or 72 weeks (patients from 248.636)
Patient Rating of Convenience of Treatment Dosing	Patients were surveyed on the convenience of Once Daily dosing versus Three Times Daily dosing	80 weeks (patients from 248.524) or 72 weeks (patients from 248.636)

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: January 15, 2008
• First Submitted That Met QC Criteria: January 25, 2008
• First Posted (Estimate): January 28, 2008

Study Record Updates

• Last Update Posted (Estimate): June 9, 2014
• Last Update Submitted That Met QC Criteria: June 3, 2014
• Last Verified: March 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: 248.633; 2007-004234-16 (EudraCT Number: EudraCT)