Pivotal Study in Advanced Parkinsons Disease Patients

Phase 3

Completed

Conditions: Parkinson Disease

Interventions: Drug: Pramipexol Extended Release
Drug: Pramipexol Immediate Release
Drug: Placebo

Registration Number: NCT00466167

Lead Sponsor: Boehringer Ingelheim

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 517

Inclusion Criteria

Male or female patient with advanced idiopathic Parkinsons disease confirmed by at least two of the following signs: resting tremor, bradykinesia, rigidity.
Parkinsons disease diagnosed for at least 2 years.
Patients 30 years of age or older at the time of diagnosis.
Modified Hoehn and Yahr stage of 2 to 4 at on-time.
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.
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).
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.
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

Atypical parkinsonian syndromes due to drugs, metabolic disorders, encephalitis or degenerative diseases
Dementia, as defined by a Mini-Mental State Exam score < 24 at screening visit
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
History of psychosis, except history of drug induced hallucinations
History of deep brain stimulation
Clinically significant Electrocardiogram abnormalities at screening visit
Clinically significant hypotension and/or symptomatic orthostatic hypotension at screening or baseline visit
Malignant melanoma or history of previously treated malignant melanoma
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
Pregnancy or breast-feeding
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
Serum levels of Aspartate Aminotransferase (Serum Glutamic-Oxaloacetic Transaminase), Alanine Aminotransferase (Serum Glutamic Pyruvic Transaminase), alkaline phosphatases or bilirubin > 2 Upper Limit of Normal
Patients with a creatinine clearance < 50 millilitres/minute
Any dopamine agonist (including pramipexole) within 4 weeks prior to baseline visit
Any medication with central dopaminergic antagonist activity within 4 weeks prior to the baseline visit
Any of the following drugs within 4 weeks prior to baseline visit: methylphenidate, cinnarizine, amphetamines
Flunarizine within 3 months prior to baseline visit
Known hypersensitivity to pramipexole or its excipients
Drug abuse according to investigators judgement, within 2 years prior to screening
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pramipexole ER	Pramipexol Extended Release	-
Pramipexole IR	Pramipexol Immediate Release	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Score at Week 18	baseline and week 18	UPDRS II+III total score on Full Analysis Set (FAS)with LOCF (Last observation carried forward), week 18 - baseline, UPDRS II+III ranging from 0 (normal) to 160 (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Percentage Off-time at Week 18	baseline and week 18	Percentage off-time based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). Off-time describes a period when the patient experiences increased parkinsonian symptoms (e.g. immobility or inability to move with ease).
Change From Baseline in Percentage On-time Without Dyskinesia at Week 18	baseline and week 18	Percentage on-time based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.
Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia at Week 18	baseline and week 18	Percentage on-time with non-troublesome dyskinesia based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.
Change From Baseline in Percentage On-time With Troublesome Dyskinesia at Week 18	baseline and week 18	Percentage on-time with troublesome dyskinesia based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.
Clinical Global Impression - Global Improvement (CGI-I) Responder	after 18 weeks of treatment	CGI-I scores ranging from '1' (very much improved) to '7' (very much worse), CGI-I responder have scoring of 1 or 2 (at least much improved)
Response in Patient Global Impression (PGI-I)	after 18 weeks of treatment	PGI-I scores ranging from '1' (very much better) to '7' (very much worse), PGI-I responder have scoring 1 or 2 (at least much better)
Change From Baseline in UPDRS I Score After 18 Weeks	baseline and 18 weeks	UPDRS I ranging from 0 (normal) to 16 (severe). UPDRS I measures Mentation, Behavior and Mood
Change From Baseline in UPDRS II Score After 18 Weeks, Average at on and Off-period	baseline and 18 weeks	UPDRS II ranging from 0 (normal) to 52 (severe). UPDRS Part II is calculated as the average of UPDRS part II at on and UPDRS part II at off-period for each of the 13 activities.
Change From Baseline in UPDRS III Score After 18 Weeks	baseline and 18 weeks	UPDRS III ranging from 0 (normal) to 108 (severe). UPDRS part III measures motor symptoms
Change From Baseline in UPDRS IV Score After 18 Weeks	baseline and 18 weeks	UPDRS IV ranging from 0 (normal) to 23 (severe). UPDRS IV measures complications of therapy
Change From Baseline in Beck's Depression Inventory (BDI) After 18 Weeks	baseline and 18 weeks	ranging from 0 (best case) to 63 (worst case)
Change From Baseline in Parkinson's Disease Sleep Scale (PDSS) After 18 Weeks	baseline and 18 weeks	ranging from 0 (worst case) to 150 (best case)
Change From Baseline in Parkinson's Disease Quality of Life Questionnaire 39 After 18 Weeks	baseline and 18 weeks	Ranging from 0 (best case) to 156 (worst case)
Change From Baseline in European Quality of Life (EuroQol) Scale After 18 Weeks	baseline and 18 weeks	ranging from 0 (worst case) to 100 (best case)
Change From Baseline in 11-point Likert Scale for Pain Related to PD at Week 18	baseline and week 18	Likert scale is a method used for the measurement of pain. The patients were asked to rate their pain related to PD by ticking the number that best described their pain on the average in the previous week, from zero for "no pain" to ten for "unbearable pain".
Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology)	baseline and week 18

Trial Locations

Locations (76): 248.525.43005 Boehringer Ingelheim Investigational Site
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Linz, Austria
248.525.82008 Boehringer Ingelheim Investigational Site
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Kyeonggi-do, Korea, Republic of
248.525.39005 Università La Sapienza di Roma
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Roma, Italy
248.525.39011 Policlinico Tor Vergata
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Roma, Italy
248.525.82001 Boehringer Ingelheim Investigational Site
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Gyeonggi-do, Korea, Republic of
248.525.82002 Boehringer Ingelheim Investigational Site
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Seoul, Korea, Republic of
248.525.82003 Boehringer Ingelheim Investigational Site
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Seoul, Korea, Republic of
248.525.82004 Boehringer Ingelheim Investigational Site
🇰🇷
Seoul, Korea, Republic of
248.525.82005 Boehringer Ingelheim Investigational Site
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Seoul, Korea, Republic of
248.525.34001 Boehringer Ingelheim Investigational Site
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Alcorcon (Madrid), Spain
248.525.34003 Boehringer Ingelheim Investigational Site
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Barcelona, Spain
248.525.34005 Boehringer Ingelheim Investigational Site
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Madrid, Spain
248.525.34004 Boehringer Ingelheim Investigational Site
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Barcelona, Spain
248.525.34002 Boehringer Ingelheim Investigational Site
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San Cugat del Valles (Barcelona), Spain
248.525.46002 Boehringer Ingelheim Investigational Site
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Nyköping, Sweden
248.525.46005 Boehringer Ingelheim Investigational Site
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Malmö, Sweden
248.525.34008 Boehringer Ingelheim Investigational Site
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Tarrasa (Barcelona), Spain
248.525.46004 Boehringer Ingelheim Investigational Site
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Stockholm, Sweden
248.525.38003 Boehringer Ingelheim Investigational Site
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Dnipropetrovsk, Ukraine
248.525.44005 Boehringer Ingelheim Investigational Site
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Barnsley, United Kingdom
248.525.44004 Boehringer Ingelheim Investigational Site
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Norwich, United Kingdom
248.525.44007 Boehringer Ingelheim Investigational Site
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Blackburn, United Kingdom
248.525.44002 Boehringer Ingelheim Investigational Site
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London, United Kingdom
248.525.42104 Boehringer Ingelheim Investigational Site
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Bratislava, Slovakia
248.525.42101 Boehringer Ingelheim Investigational Site
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Trnava, Slovakia
248.525.07007 Boehringer Ingelheim Investigational Site
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Moscow, Russian Federation
248.525.07001 Boehringer Ingelheim Investigational Site
🇷🇺
Moscow, Russian Federation
248.525.07002 Boehringer Ingelheim Investigational Site
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Moscow, Russian Federation
248.525.42001 Boehringer Ingelheim Investigational Site
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Praha, Czech Republic
248.525.63207 Manila Doctors Hospital
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Manila, Philippines
248.525.48001 Boehringer Ingelheim Investigational Site
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Gdansk, Poland
248.525.48003 Boehringer Ingelheim Investigational Site
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Krakow, Poland
248.525.07006 Boehringer Ingelheim Investigational Site
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St. Petersburg, Russian Federation
248.525.42103 Boehringer Ingelheim Investigational Site
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Dubnica nad Vahom, Slovakia
248.525.42003 Boehringer Ingelheim Investigational Site
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Pardubice, Czech Republic
248.525.48002 Wolski Hospital Dr. Anna Gostynska
🇵🇱
Warsaw, Poland
248.525.07005 Boehringer Ingelheim Investigational Site
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St. Petersburg, Russian Federation
248.525.38002 Boehringer Ingelheim Investigational Site
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Kiev, Ukraine
248.525.38004 Boehringer Ingelheim Investigational Site
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Kiev, Ukraine
248.525.42005 Boehringer Ingelheim Investigational Site
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Rakovnik, Czech Republic
248.525.63208 University of the East Ramon Magsaysay Memorial Medical Ctr
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Quezon, Philippines
248.525.38006 Boehringer Ingelheim Investigational Site
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Kharkiv, Ukraine
248.525.07003 Boehringer Ingelheim Investigational Site
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Moscow, Russian Federation
248.525.39002 Università Federico II
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Napoli, Italy
248.525.39008 Azienda Ospedaliera Pisana- Università degli Studi di Pisa
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Pisa, Italy
248.525.42004 Boehringer Ingelheim Investigational Site
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Valasske Mezirici, Czech Republic
248.525.36003 Boehringer Ingelheim Investigational Site
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Kecskemét, Hungary
248.525.91004 National Institute of Mental Health & Neuro Sciences
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Bangalore, India
248.525.39009 Ce.S.I.
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Chieti, Italy
248.525.42002 Boehringer Ingelheim Investigational Site
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Rychnov nad Kneznou, Czech Republic
248.525.91002 Apollo Hospital
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Chennai, India
248.525.91001 Institute of Human Behaviour & Allied Sciences
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Delhi, India
248.525.91003 Nizam's Institute of Medical Sciences
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Hyderabad, India
248.525.91005 Mallikatta Neuro Research Center
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Karnataka, India
248.525.63206 Metropolitan Medical Center
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Manila, Philippines
248.525.39001 Policlinico di Catania
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Catania, Italy
248.525.39010 Campus Universitario Germaneto
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Catanzaro, Italy
248.525.39007 Ospedale della Misericordia
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Grosseto, Italy
248.525.36005 Boehringer Ingelheim Investigational Site
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Györ, Hungary
248.525.36006 Boehringer Ingelheim Investigational Site
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Szeged, Hungary
248.525.36004 Boehringer Ingelheim Investigational Site
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Veszprem, Hungary
248.525.91007 Boehringer Ingelheim Investigational Site
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Indore, India
248.525.91006 King Edward Memorial Hospital & Research Centre
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Pune, India
248.525.82007 Boehringer Ingelheim Investigational Site
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Pusan, Korea, Republic of
248.525.82006 Boehringer Ingelheim Investigational Site
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Seoul, Korea, Republic of
248.525.63201 The Medical City
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Pasig, Philippines
248.525.63204 St Lukes Medical Center
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Quezon, Philippines
248.525.63210 Makati Medical Center
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Makati City, Philippines
248.525.63202 Chinese General Hospital
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Manila, Philippines
248.525.63205 Jose Reyes Memorial Medical Center
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Manila, Philippines
248.525.38001 Boehringer Ingelheim Investigational Site
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Zaporozhye, Ukraine
248.525.42105 Boehringer Ingelheim Investigational Site
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Bratislava, Slovakia
248.525.46001 Boehringer Ingelheim Investigational Site
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Stockholm, Sweden
248.525.44003 Boehringer Ingelheim Investigational Site
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Salford, United Kingdom
248.525.38005 Boehringer Ingelheim Investigational Site
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Zaporizhzhya, Ukraine
248.525.07004 Boehringer Ingelheim Investigational Site
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Moscow, Russian Federation