MedPath

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

Phase 3
Completed
Conditions
Parkinson Disease
Interventions
Registration Number
NCT00558025
Lead Sponsor
Boehringer Ingelheim
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
156
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Pramipexole Extended Release (ER)Pramipexole Extended ReleasePramipexole Extended Release (ER) once daily
Pramipexole Immediate Release (IR)Pramipexole Immediate ReleasePramipexole Immediate Release (IR) once daily
Primary Outcome Measures
NameTimeMethod
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)from baseline to week 9

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)

Secondary Outcome Measures
NameTimeMethod
Percentage of Patients Who Successfully Switched From Pramipexole IR to Pramipexole ER With no Dose Adaptation, FAS (LOCF)from baseline to week 4

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).

Change From Baseline in UPDRS Part II+III Total Score at Week 9, FAS (LOCF)Baseline and week 9

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)

Change From Baseline in UPDRS Part II Total Score at Week 9, FAS (LOCF)Baseline and week 9

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)

Change From Baseline in UPDRS Part III Total Score at Week 9, FAS (LOCF)Baseline and week 9

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)

Clinical Global Impression - Improvement (CGI-I), FAS (LOCF)Week 9

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'

Patient Global Impression - Improvement (PGI-I), FAS (LOCF)Week 9

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'

Pramipexole Dose Adaptation, FAS (LOCF)Week 9

Patients with increase in daily Pramipexole dose on FAS

Final Pramipexole Dose (mg) After 9 Weeks, Treated SetWeek 9

The mean final daily Pramipexole dose is displayed

Trial Locations

Locations (36)

248.636.3307C Boehringer Ingelheim Investigational Site

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Bron cedex, France

248.636.31005 Boehringer Ingelheim Investigational Site

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's-hertogenbosch, Netherlands

248.636.3303B Boehringer Ingelheim Investigational Site

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Aix en Provence, France

248.636.3308C Boehringer Ingelheim Investigational Site

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Lille cedex, France

248.636.3302A Boehringer Ingelheim Investigational Site

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Marseille cedex 5, France

248.636.31002 Boehringer Ingelheim Investigational Site

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Geldrop, Netherlands

248.636.31006 Boehringer Ingelheim Investigational Site

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Maastricht, Netherlands

248.636.3312A Boehringer Ingelheim Investigational Site

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Rouen, France

248.636.3303A Boehringer Ingelheim Investigational Site

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Aix en Provence, France

248.636.49003 Boehringer Ingelheim Investigational Site

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Berlin-Steglitz, Germany

248.636.31003 Boehringer Ingelheim Investigational Site

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Helmond, Netherlands

248.636.31004 Boehringer Ingelheim Investigational Site

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Nijmegen, Netherlands

248.636.31001 Boehringer Ingelheim Investigational Site

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Sittard, Netherlands

248.636.3303C Boehringer Ingelheim Investigational Site

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Aix en Provence, France

248.636.3313A Boehringer Ingelheim Investigational Site

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Dijon cedex, France

248.636.3309B Boehringer Ingelheim Investigational Site

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Clermont Ferrand, France

248.636.3308B Boehringer Ingelheim Investigational Site

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Lille cedex, France

248.636.3304A Boehringer Ingelheim Investigational Site

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Evreux, France

248.636.3305B Boehringer Ingelheim Investigational Site

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Créteil, France

248.636.3305A Boehringer Ingelheim Investigational Site

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Créteil, France

248.636.3308D Boehringer Ingelheim Investigational Site

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Lille cedex, France

248.636.3308E Boehringer Ingelheim Investigational Site

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Lille cedex, France

248.636.3306B Boehringer Ingelheim Investigational Site

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Montpellier, France

248.636.3311A Boehringer Ingelheim Investigational Site

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Strasbourg, France

248.636.3312B Boehringer Ingelheim Investigational Site

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Rouen, France

248.636.49006 Boehringer Ingelheim Investigational Site

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Achim bei Bremen, Germany

248.636.3301A Boehringer Ingelheim Investigational Site

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Toulouse cedex, France

248.636.3301D Boehringer Ingelheim Investigational Site

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Toulouse cedex, France

248.636.3301B Boehringer Ingelheim Investigational Site

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Toulouse cedex, France

248.636.49004 Boehringer Ingelheim Investigational Site

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Berlin, Germany

248.636.49002 Boehringer Ingelheim Investigational Site

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Gera, Germany

248.636.49008 Boehringer Ingelheim Investigational Site

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Berlin, Germany

248.636.49001 Boehringer Ingelheim Investigational Site

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Karlsruhe, Germany

248.636.49007 Boehringer Ingelheim Investigational Site

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Berlin, Germany

248.636.49005 Boehringer Ingelheim Investigational Site

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Unterhaching, Germany

248.636.3302B Boehringer Ingelheim Investigational Site

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Marseille cedex 5, France

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