Clinical trial NCT00558025: Overnight Switch Trial From Pramipexole IR to Pramipexole ER in Patients With Early Parkinson Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson Disease
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2007-11-14
Enrollment: 156
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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)
timeFrame: from baseline to week 9
Secondary outcomes:
measure: Percentage of Patients Who Successfully Switched From Pramipexole IR to Pramipexole ER With no Dose Adaptation, FAS (LOCF)
timeFrame: from baseline to week 4
measure: Change From Baseline in UPDRS Part II+III Total Score at Week 9, FAS (LOCF)
timeFrame: Baseline and week 9
measure: Change From Baseline in UPDRS Part II Total Score at Week 9, FAS (LOCF)
timeFrame: Baseline and week 9
measure: Change From Baseline in UPDRS Part III Total Score at Week 9, FAS (LOCF)
timeFrame: Baseline and week 9
measure: Clinical Global Impression - Improvement (CGI-I), FAS (LOCF)
timeFrame: Week 9
measure: Patient Global Impression - Improvement (PGI-I), FAS (LOCF)
timeFrame: Week 9
measure: Pramipexole Dose Adaptation, FAS (LOCF)
timeFrame: Week 9
measure: Final Pramipexole Dose (mg) After 9 Weeks, Treated Set
timeFrame: Week 9
Other outcomes:
Locations:
city: Aix en Provence
country: France
facility: 248.636.3303A Boehringer Ingelheim Investigational Site
city: Aix en Provence
country: France
facility: 248.636.3303B Boehringer Ingelheim Investigational Site
city: Aix en Provence
country: France
facility: 248.636.3303C Boehringer Ingelheim Investigational Site
city: Bron cedex
country: France
facility: 248.636.3307C Boehringer Ingelheim Investigational Site
city: Clermont Ferrand
country: France
facility: 248.636.3309B Boehringer Ingelheim Investigational Site
city: Créteil
country: France
facility: 248.636.3305A Boehringer Ingelheim Investigational Site
city: Créteil
country: France
facility: 248.636.3305B Boehringer Ingelheim Investigational Site
city: Dijon cedex
country: France
facility: 248.636.3313A Boehringer Ingelheim Investigational Site
city: Evreux
country: France
facility: 248.636.3304A Boehringer Ingelheim Investigational Site
city: Lille cedex
country: France
facility: 248.636.3308B Boehringer Ingelheim Investigational Site
city: Lille cedex
country: France
facility: 248.636.3308C Boehringer Ingelheim Investigational Site
city: Lille cedex
country: France
facility: 248.636.3308D Boehringer Ingelheim Investigational Site
city: Lille cedex
country: France
facility: 248.636.3308E Boehringer Ingelheim Investigational Site
city: Marseille cedex 5
country: France
facility: 248.636.3302A Boehringer Ingelheim Investigational Site
city: Marseille cedex 5
country: France
facility: 248.636.3302B Boehringer Ingelheim Investigational Site
city: Montpellier
country: France
facility: 248.636.3306B Boehringer Ingelheim Investigational Site
city: Rouen
country: France
facility: 248.636.3312A Boehringer Ingelheim Investigational Site
city: Rouen
country: France
facility: 248.636.3312B Boehringer Ingelheim Investigational Site
city: Strasbourg
country: France
facility: 248.636.3311A Boehringer Ingelheim Investigational Site
city: Toulouse cedex
country: France
facility: 248.636.3301A Boehringer Ingelheim Investigational Site
city: Toulouse cedex
country: France
facility: 248.636.3301B Boehringer Ingelheim Investigational Site
city: Toulouse cedex
country: France
facility: 248.636.3301D Boehringer Ingelheim Investigational Site
city: Achim bei Bremen
country: Germany
facility: 248.636.49006 Boehringer Ingelheim Investigational Site
city: Berlin-Steglitz
country: Germany
facility: 248.636.49003 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 248.636.49004 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 248.636.49007 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 248.636.49008 Boehringer Ingelheim Investigational Site
city: Gera
country: Germany
facility: 248.636.49002 Boehringer Ingelheim Investigational Site
city: Karlsruhe
country: Germany
facility: 248.636.49001 Boehringer Ingelheim Investigational Site
city: Unterhaching
country: Germany
facility: 248.636.49005 Boehringer Ingelheim Investigational Site
city: 's-hertogenbosch
country: Netherlands
facility: 248.636.31005 Boehringer Ingelheim Investigational Site
city: Geldrop
country: Netherlands
facility: 248.636.31002 Boehringer Ingelheim Investigational Site
city: Helmond
country: Netherlands
facility: 248.636.31003 Boehringer Ingelheim Investigational Site
city: Maastricht
country: Netherlands
facility: 248.636.31006 Boehringer Ingelheim Investigational Site
city: Nijmegen
country: Netherlands
facility: 248.636.31004 Boehringer Ingelheim Investigational Site
city: Sittard
country: Netherlands
facility: 248.636.31001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: