Overnight Switch Trial From Pramipexole IR to Pramipexole ER in Patients With Early Parkinson Disease

A Double-blind, Double-dummy, Randomized, Parallel Groups Study to Assess the Efficacy, Safety and Tolerability of Switching Patients With Early Parkinson's Disease (PD) From Pramipexole IR to Pramipexole ER or Pramipexole IR

The objectives of this trial conducted in early Parkinson's disease (PD) patients are:

• To assess if patients with early Parkinson's disease (PD) can be successfully switched (overnight switching) from Pramipexole (PPX) Immediate Release (IR) to Pramipexole Extended Release (ER). A successful switch at a specific visit is defined as no worsening of the Unified Parkinsons Disease Rating Scale (UPDRS) parts II+III score by more than 15% from baseline and no drug-related adverse events leading to withdrawal;
• To establish if this successful switch can be obtained with or without dose-adaptation;
• To provide information about the conversion ratio (mg:mg) from Pramipexole IR to Pramipexole ER.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Pramipexole Extended Release; Drug: Pramipexole Immediate Release

• Study Type: Interventional
• Enrollment (Actual): 156
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Aix en Provence, France
    • 248.636.3303A Boehringer Ingelheim Investigational Site
  • Aix en Provence, France
    • 248.636.3303B Boehringer Ingelheim Investigational Site
  • Aix en Provence, France
    • 248.636.3303C Boehringer Ingelheim Investigational Site
  • Bron cedex, France
    • 248.636.3307C Boehringer Ingelheim Investigational Site
  • Clermont Ferrand, France
    • 248.636.3309B Boehringer Ingelheim Investigational Site
  • Créteil, France
    • 248.636.3305A Boehringer Ingelheim Investigational Site
  • Créteil, France
    • 248.636.3305B Boehringer Ingelheim Investigational Site
  • Dijon cedex, France
    • 248.636.3313A Boehringer Ingelheim Investigational Site
  • Evreux, France
    • 248.636.3304A Boehringer Ingelheim Investigational Site
  • Lille cedex, France
    • 248.636.3308B Boehringer Ingelheim Investigational Site
  • Lille cedex, France
    • 248.636.3308C Boehringer Ingelheim Investigational Site
  • Lille cedex, France
    • 248.636.3308D Boehringer Ingelheim Investigational Site
  • Lille cedex, France
    • 248.636.3308E Boehringer Ingelheim Investigational Site
  • Marseille cedex 5, France
    • 248.636.3302A Boehringer Ingelheim Investigational Site
  • Marseille cedex 5, France
    • 248.636.3302B Boehringer Ingelheim Investigational Site
  • Montpellier, France
    • 248.636.3306B Boehringer Ingelheim Investigational Site
  • Rouen, France
    • 248.636.3312A Boehringer Ingelheim Investigational Site
  • Rouen, France
    • 248.636.3312B Boehringer Ingelheim Investigational Site
  • Strasbourg, France
    • 248.636.3311A Boehringer Ingelheim Investigational Site
  • Toulouse cedex, France
    • 248.636.3301A Boehringer Ingelheim Investigational Site
  • Toulouse cedex, France
    • 248.636.3301B Boehringer Ingelheim Investigational Site
  • Toulouse cedex, France
    • 248.636.3301D Boehringer Ingelheim Investigational Site
• Germany
  • Achim bei Bremen, Germany
    • 248.636.49006 Boehringer Ingelheim Investigational Site
  • Berlin, Germany
    • 248.636.49004 Boehringer Ingelheim Investigational Site
  • Berlin, Germany
    • 248.636.49007 Boehringer Ingelheim Investigational Site
  • Berlin, Germany
    • 248.636.49008 Boehringer Ingelheim Investigational Site
  • Berlin-Steglitz, Germany
    • 248.636.49003 Boehringer Ingelheim Investigational Site
  • Gera, Germany
    • 248.636.49002 Boehringer Ingelheim Investigational Site
  • Karlsruhe, Germany
    • 248.636.49001 Boehringer Ingelheim Investigational Site
  • Unterhaching, Germany
    • 248.636.49005 Boehringer Ingelheim Investigational Site
• Netherlands
  • 's-hertogenbosch, Netherlands
    • 248.636.31005 Boehringer Ingelheim Investigational Site
  • Geldrop, Netherlands
    • 248.636.31002 Boehringer Ingelheim Investigational Site
  • Helmond, Netherlands
    • 248.636.31003 Boehringer Ingelheim Investigational Site
  • Maastricht, Netherlands
    • 248.636.31006 Boehringer Ingelheim Investigational Site
  • Nijmegen, Netherlands
    • 248.636.31004 Boehringer Ingelheim Investigational Site
  • Sittard, Netherlands
    • 248.636.31001 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. Male or female patient with idiopathic Parkinson's disease (PD) confirmed by at least two of the following signs: resting tremor, bradykinesia, rigidity.
2. Parkinson's disease diagnosed within 5 years.
3. Patients 30 years of age or older at the time of diagnosis.
4. Modified Hoehn and Yahr stage of 1 to 3.
5. Patients receiving pramipexole IR for at least three months prior to baseline visit (randomization visit, V2).
6. Pramipexole dose should be optimized (according investigator¿s judgement), greater or equal to 1.5 mg/day, stable and equally divided 3 times per day, for a least 4 weeks prior to baseline visit (V2).
7. Patients willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
8. Signed informed consent obtained before any study procedures are carried out in accordance with International Conference on Harmonization - Good Clinical Practice (ICH-GCP) guidelines and local legislation).

Exclusion Criteria:

1. Motor complications under levodopa therapy at V1.
2. Atypical parkinsonian syndromes due to drugs, metabolic disorders, encephalitis or degenerative diseases.
3. Dementia, as defined by a Mini-Mental State Exam score < 24 at V1
4. Any psychiatric disorder according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria
5. History of psychosis, except history of drug induced hallucinations
6. Clinically significant electrocardiogram (ECG) abnormalities at V1.
7. Clinically significant hypotension either at screening visit or at baseline visit.
8. Malignant melanoma or history of previously treated malignant melanoma.
9. Any other clinically significant disease
10. Pregnancy or breast-feeding.
11. Sexually active female of childbearing potential
12. Serum levels of Aspartate Aminotransferase (Serum Glutamic Oxaloacetic Transaminase) (AST (SGOT)), Alanine Aminotransferase (Serum Glutamate Pyruvate Transaminase) (ALT (SGPT)), alkaline phosphatases or bilirubin > 2 Upper Limit of Normal (ULN) (on screening lab test).
13. Patients with a creatinine clearance < 50 mL/min
14. Any dopamine agonist (except pramipexole IR) within three months prior to baseline visit.
15. History of discontinuation of treatment with pramipexole IR
16. Previous treatment with pramipexole ER.
17. Any medication (including intra-muscular formulations) with central dopaminergic antagonist activity within 4 weeks prior to the baseline visit (i.e. typical neuroleptics, atypical antipsychotics, reserpine, methyldopa, centrally-active antiemetics, etc).
18. Any of the following drugs within 4 weeks prior to the baseline visit: methylphenidate, cinnarizine, amphetamines.
19. Flunarizine within 3 months prior to baseline visit.
20. Known hypersensitivity to Pramipexole or its excipients.
21. Drug abuse (including alcohol), according to Investigator¿s judgement, within 2 years prior to screening.
22. Participation in other investigational drug studies or use of other investigational drugs within 4 weeks or five times the half-life of the investigational drug (whichever is longer) prior to baseline visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pramipexole Extended Release (ER); Pramipexole Extended Release (ER) once daily	Drug: Pramipexole Extended Release
Experimental: Pramipexole Immediate Release (IR); Pramipexole Immediate Release (IR) once daily	Drug: Pramipexole Immediate Release

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Who Successfully Switched From Pramipexole Immediate Release (IR) to Pramipexole ER After a Possible Dose Adaptation, Full Analysis Set (FAS), Last Observation Carried Forward (LOCF)	A successful switch was defined by no change of the Unified Parkinson's Disease Rating Scale (UPDRS) II+III by more than 15% from baseline to week 9, UPDRS II+III score ranging from 0 (no impairment) to 160 (worst impairment)	from baseline to week 9

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Who Successfully Switched From Pramipexole IR to Pramipexole ER With no Dose Adaptation, FAS (LOCF)	A successful switch was defined by no change of the UPDRS II+III by more than 15% from baseline to week 4, UPDRS II+III score ranging from 0 (no impairment) to 160 (worst impairment).	from baseline to week 4
Change From Baseline in UPDRS Part II+III Total Score at Week 9, FAS (LOCF)	Unified Parkinson's Disease Rating Scale part II+III total score on FAS, Week 9 - baseline, UPDRS II+III score ranging from 0 (no impairment) to 160 (worst impairment)	Baseline and week 9
Change From Baseline in UPDRS Part II Total Score at Week 9, FAS (LOCF)	Unified Parkinson's Disease Rating Scale part II total score on FAS, Week 9 - baseline, UPDRS II score ranging from 0 (no impairment) to 52 (worst impairment)	Baseline and week 9
Change From Baseline in UPDRS Part III Total Score at Week 9, FAS (LOCF)	Unified Parkinson's Disease Rating Scale part III total score on FAS, week 9 - baseline, UPDRS II+III score ranging from 0 (no impairment) to 108 (worst impairment)	Baseline and week 9
Clinical Global Impression - Improvement (CGI-I), FAS (LOCF)	Clinical Global Impression - Improvement on FAS, CGI-I was rated from 1: very much improved, to 7: very much worse, CGI-I responder are defined as being rated as 'unchanged', 'minimally improved', 'much improved', or 'very much improved', CGI-I non-responder are defined as being rated 'minimally worse', 'much worse' or 'very much worse'	Week 9
Patient Global Impression - Improvement (PGI-I), FAS (LOCF)	Patient Global Impression - Improvement on FAS, PGI-I was rated from 1: very much better, to 7: very much worse, PGI-I responder are defined as being rated as 'unchanged', 'minimally better', 'much better', or 'very much better', PGI-I non-responder are defined as being rated as 'minimally worse', 'much worse', or 'very much worse'	Week 9
Pramipexole Dose Adaptation, FAS (LOCF)	Patients with increase in daily Pramipexole dose on FAS	Week 9
Final Pramipexole Dose (mg) After 9 Weeks, Treated Set	The mean final daily Pramipexole dose is displayed	Week 9

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: November 12, 2007
• First Submitted That Met QC Criteria: November 13, 2007
• First Posted (Estimate): November 14, 2007

Study Record Updates

• Last Update Posted (Estimate): May 16, 2014
• Last Update Submitted That Met QC Criteria: May 7, 2014
• Last Verified: May 1, 2012

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: 248.636; Eudract 2007-003353-90