Clinical trial NCT00466167: Pivotal Study in Advanced Parkinsons Disease Patients
Official title: A Double-blind, Double-dummy, Placebo-controlled, Randomized, Three Parallel Groups Study Comparing the Efficacy, Safety and Tolerability of Pramipexole Extended Release (ER) Versus Placebo and Versus Pramipexole Immediate Release (IR) Administered Orally Over a 26-week Maintenance Phase in L-Dopa+ Treated Patients With Advanced Parkinsons Disease (PD).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson Disease
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2007-04-27
Enrollment: 517
Sex: ALL
Minimum age (years): 32
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The general aim of this trial is to determine the efficacy (as measured by the change from baseline to the end of the maintenance phase in the total score for Unified Parkinsons Disease Rating Scale Parts II and III combined), safety, and tolerability of pramipexole ER, in daily doses from 0.375 milligram to 4.5 milligram once a day, in comparison to placebo, in Levodopa combined with a Dopa-Decarboxylase-inhibitor treated Parkinson patients with advanced Parkinsons Disease and motor fluctuations.

In addition, a numerical comparison of the efficacy of pramipexole extended release versus pramipexole immediate release will be done.

The efficacy of pramipexole immediate release will also be compared to placebo, for assay sensitivity.


Eligibility criteria: Inclusion Criteria:

1. Male or female patient with advanced idiopathic Parkinsons disease confirmed by at least two of the following signs: resting tremor, bradykinesia, rigidity.
2. Parkinsons disease diagnosed for at least 2 years.
3. Patients 30 years of age or older at the time of diagnosis.
4. Modified Hoehn and Yahr stage of 2 to 4 at on-time.
5. Treatment with standard or controlled release Levodopa combined with a Dopa-Decarboxylase-inhibitor, or with Levodopa combined with a Dopa-Decarboxylase-inhibitor/entacapone, at an optimised dose according to investigators judgement, this dose being stable for at least 4 weeks prior to baseline visit.
6. Motor fluctuations, with at least 2 cumulative hours of off-time every day during waking hours (documented on a patient diary completed for 2 consecutive days before baseline visit).
7. Patient willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. In particular, after training, it has to be documented at baseline visit that the patient is able to recognise the off-time and on-time periods during waking hours and that the patient (or a family member or a guardian) is able to record them accurately in the patient diary.
8. Signed informed consent obtained before any study procedures are carried out (in accordance with International Conference on Harmonisation-Good Clinical Practice guidelines and local legislation).

Exclusion Criteria:

1. Atypical parkinsonian syndromes due to drugs, metabolic disorders, encephalitis or degenerative diseases
2. Dementia, as defined by a Mini-Mental State Exam score \< 24 at screening visit
3. Any psychiatric disorder according to Diagnostic and Statistical Manual of Mental Disorders 4th edition 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 Electrocardiogram abnormalities at screening visit
7. Clinically significant hypotension and/or symptomatic orthostatic hypotension at screening or baseline visit
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 for at least one month prior to the screening visit and throughout the study period
12. Serum levels of Aspartate Aminotransferase (Serum Glutamic-Oxaloacetic Transaminase), Alanine Aminotransferase (Serum Glutamic Pyruvic Transaminase), alkaline phosphatases or bilirubin \> 2 Upper Limit of Normal
13. Patients with a creatinine clearance \< 50 millilitres/minute
14. Any dopamine agonist (including pramipexole) within 4 weeks prior to baseline visit
15. Any medication with central dopaminergic antagonist activity within 4 weeks prior to the baseline visit
16. Any of the following drugs within 4 weeks prior to baseline visit: methylphenidate, cinnarizine, amphetamines
17. Flunarizine within 3 months prior to baseline visit
18. Known hypersensitivity to pramipexole or its excipients
19. Drug abuse according to investigators judgement, within 2 years prior to screening
20. Participation in other investigational drug studies, 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 visit

Primary outcomes:
measure: Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Score at Week 18
timeFrame: baseline and week 18
Secondary outcomes:
measure: Change From Baseline in Percentage Off-time at Week 18
timeFrame: baseline and week 18
measure: Change From Baseline in Percentage On-time Without Dyskinesia at Week 18
timeFrame: baseline and week 18
measure: Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia at Week 18
timeFrame: baseline and week 18
measure: Change From Baseline in Percentage On-time With Troublesome Dyskinesia at Week 18
timeFrame: baseline and week 18
measure: Clinical Global Impression - Global Improvement (CGI-I) Responder
timeFrame: after 18 weeks of treatment
measure: Response in Patient Global Impression (PGI-I)
timeFrame: after 18 weeks of treatment
measure: Change From Baseline in UPDRS I Score After 18 Weeks
timeFrame: baseline and 18 weeks
measure: Change From Baseline in UPDRS II Score After 18 Weeks, Average at on and Off-period
timeFrame: baseline and 18 weeks
measure: Change From Baseline in UPDRS III Score After 18 Weeks
timeFrame: baseline and 18 weeks
measure: Change From Baseline in UPDRS IV Score After 18 Weeks
timeFrame: baseline and 18 weeks
measure: Change From Baseline in Beck's Depression Inventory (BDI) After 18 Weeks
timeFrame: baseline and 18 weeks
measure: Change From Baseline in Parkinson's Disease Sleep Scale (PDSS) After 18 Weeks
timeFrame: baseline and 18 weeks
measure: Change From Baseline in Parkinson's Disease Quality of Life Questionnaire 39 After 18 Weeks
timeFrame: baseline and 18 weeks
measure: Change From Baseline in European Quality of Life (EuroQol) Scale After 18 Weeks
timeFrame: baseline and 18 weeks
measure: Change From Baseline in 11-point Likert Scale for Pain Related to PD at Week 18
timeFrame: baseline and week 18
measure: Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology)
timeFrame: baseline and week 18
Other outcomes:
Locations:
city: Linz
country: Austria
facility: 248.525.43005 Boehringer Ingelheim Investigational Site
city: Pardubice
country: Czech Republic
facility: 248.525.42003 Boehringer Ingelheim Investigational Site
city: Praha
country: Czech Republic
facility: 248.525.42001 Boehringer Ingelheim Investigational Site
city: Rakovnik
country: Czech Republic
facility: 248.525.42005 Boehringer Ingelheim Investigational Site
city: Rychnov nad Kneznou
country: Czech Republic
facility: 248.525.42002 Boehringer Ingelheim Investigational Site
city: Valasske Mezirici
country: Czech Republic
facility: 248.525.42004 Boehringer Ingelheim Investigational Site
city: Györ
country: Hungary
facility: 248.525.36005 Boehringer Ingelheim Investigational Site
city: Kecskemét
country: Hungary
facility: 248.525.36003 Boehringer Ingelheim Investigational Site
city: Szeged
country: Hungary
facility: 248.525.36006 Boehringer Ingelheim Investigational Site
city: Veszprem
country: Hungary
facility: 248.525.36004 Boehringer Ingelheim Investigational Site
city: Bangalore
country: India
facility: 248.525.91004 National Institute of Mental Health & Neuro Sciences
city: Chennai
country: India
facility: 248.525.91002 Apollo Hospital
city: Delhi
country: India
facility: 248.525.91001 Institute of Human Behaviour & Allied Sciences
city: Hyderabad
country: India
facility: 248.525.91003 Nizam's Institute of Medical Sciences
city: Indore
country: India
facility: 248.525.91007 Boehringer Ingelheim Investigational Site
city: Karnataka
country: India
facility: 248.525.91005 Mallikatta Neuro Research Center
city: Pune
country: India
facility: 248.525.91006 King Edward Memorial Hospital & Research Centre
city: Catania
country: Italy
facility: 248.525.39001 Policlinico di Catania
city: Catanzaro
country: Italy
facility: 248.525.39010 Campus Universitario Germaneto
city: Chieti
country: Italy
facility: 248.525.39009 Ce.S.I.
city: Grosseto
country: Italy
facility: 248.525.39007 Ospedale della Misericordia
city: Napoli
country: Italy
facility: 248.525.39002 Università Federico II
city: Pisa
country: Italy
facility: 248.525.39008 Azienda Ospedaliera Pisana- Università degli Studi di Pisa
city: Roma
country: Italy
facility: 248.525.39005 Università La Sapienza di Roma
city: Roma
country: Italy
facility: 248.525.39011 Policlinico Tor Vergata
city: Gyeonggi-do
country: Korea, Republic of
facility: 248.525.82001 Boehringer Ingelheim Investigational Site
city: Kyeonggi-do
country: Korea, Republic of
facility: 248.525.82008 Boehringer Ingelheim Investigational Site
city: Pusan
country: Korea, Republic of
facility: 248.525.82007 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 248.525.82002 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 248.525.82003 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 248.525.82004 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 248.525.82005 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 248.525.82006 Boehringer Ingelheim Investigational Site
city: Makati City
country: Philippines
facility: 248.525.63210 Makati Medical Center
city: Manila
country: Philippines
facility: 248.525.63202 Chinese General Hospital
city: Manila
country: Philippines
facility: 248.525.63205 Jose Reyes Memorial Medical Center
city: Manila
country: Philippines
facility: 248.525.63206 Metropolitan Medical Center
city: Manila
country: Philippines
facility: 248.525.63207 Manila Doctors Hospital
city: Pasig
country: Philippines
facility: 248.525.63201 The Medical City
city: Quezon
country: Philippines
facility: 248.525.63204 St Lukes Medical Center
city: Quezon
country: Philippines
facility: 248.525.63208 University of the East Ramon Magsaysay Memorial Medical Ctr
city: Gdansk
country: Poland
facility: 248.525.48001 Boehringer Ingelheim Investigational Site
city: Krakow
country: Poland
facility: 248.525.48003 Boehringer Ingelheim Investigational Site
city: Warsaw
country: Poland
facility: 248.525.48002 Wolski Hospital Dr. Anna Gostynska
city: Moscow
country: Russian Federation
facility: 248.525.07001 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 248.525.07002 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 248.525.07003 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 248.525.07004 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 248.525.07007 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 248.525.07005 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 248.525.07006 Boehringer Ingelheim Investigational Site
city: Bratislava
country: Slovakia
facility: 248.525.42104 Boehringer Ingelheim Investigational Site
city: Bratislava
country: Slovakia
facility: 248.525.42105 Boehringer Ingelheim Investigational Site
city: Dubnica nad Vahom
country: Slovakia
facility: 248.525.42103 Boehringer Ingelheim Investigational Site
city: Trnava
country: Slovakia
facility: 248.525.42101 Boehringer Ingelheim Investigational Site
city: Alcorcon (Madrid)
country: Spain
facility: 248.525.34001 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 248.525.34003 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 248.525.34004 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 248.525.34005 Boehringer Ingelheim Investigational Site
city: San Cugat del Valles (Barcelona)
country: Spain
facility: 248.525.34002 Boehringer Ingelheim Investigational Site
city: Tarrasa (Barcelona)
country: Spain
facility: 248.525.34008 Boehringer Ingelheim Investigational Site
city: Malmö
country: Sweden
facility: 248.525.46005 Boehringer Ingelheim Investigational Site
city: Nyköping
country: Sweden
facility: 248.525.46002 Boehringer Ingelheim Investigational Site
city: Stockholm
country: Sweden
facility: 248.525.46001 Boehringer Ingelheim Investigational Site
city: Stockholm
country: Sweden
facility: 248.525.46004 Boehringer Ingelheim Investigational Site
city: Dnipropetrovsk
country: Ukraine
facility: 248.525.38003 Boehringer Ingelheim Investigational Site
city: Kharkiv
country: Ukraine
facility: 248.525.38006 Boehringer Ingelheim Investigational Site
city: Kiev
country: Ukraine
facility: 248.525.38002 Boehringer Ingelheim Investigational Site
city: Kiev
country: Ukraine
facility: 248.525.38004 Boehringer Ingelheim Investigational Site
city: Zaporizhzhya
country: Ukraine
facility: 248.525.38005 Boehringer Ingelheim Investigational Site
city: Zaporozhye
country: Ukraine
facility: 248.525.38001 Boehringer Ingelheim Investigational Site
city: Barnsley
country: United Kingdom
facility: 248.525.44005 Boehringer Ingelheim Investigational Site
city: Blackburn
country: United Kingdom
facility: 248.525.44007 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 248.525.44002 Boehringer Ingelheim Investigational Site
city: Norwich
country: United Kingdom
facility: 248.525.44004 Boehringer Ingelheim Investigational Site
city: Salford
country: United Kingdom
facility: 248.525.44003 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: