Pivotal Study in Advanced Parkinsons Disease Patients

June 24, 2014 updated by: Boehringer Ingelheim

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).

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

517

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

32 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Interventional Model: Parallel Assignment

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
Other: Pramipexole ER
Drug: Pramipexol Extended Release
Other: Pramipexole IR
Drug: Pramipexol Immediate Release

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Score at Week 18
Time Frame: 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
baseline and week 18

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Percentage Off-time at Week 18
Time Frame: 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).
baseline and week 18
Change From Baseline in Percentage On-time Without Dyskinesia at Week 18
Time Frame: 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.
baseline and week 18
Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia at Week 18
Time Frame: 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.
baseline and week 18
Change From Baseline in Percentage On-time With Troublesome Dyskinesia at Week 18
Time Frame: 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.
baseline and week 18
Clinical Global Impression - Global Improvement (CGI-I) Responder
Time Frame: 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)
after 18 weeks of treatment
Response in Patient Global Impression (PGI-I)
Time Frame: 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)
after 18 weeks of treatment
Change From Baseline in UPDRS I Score After 18 Weeks
Time Frame: baseline and 18 weeks
UPDRS I ranging from 0 (normal) to 16 (severe). UPDRS I measures Mentation, Behavior and Mood
baseline and 18 weeks
Change From Baseline in UPDRS II Score After 18 Weeks, Average at on and Off-period
Time Frame: 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.
baseline and 18 weeks
Change From Baseline in UPDRS III Score After 18 Weeks
Time Frame: baseline and 18 weeks
UPDRS III ranging from 0 (normal) to 108 (severe). UPDRS part III measures motor symptoms
baseline and 18 weeks
Change From Baseline in UPDRS IV Score After 18 Weeks
Time Frame: baseline and 18 weeks
UPDRS IV ranging from 0 (normal) to 23 (severe). UPDRS IV measures complications of therapy
baseline and 18 weeks
Change From Baseline in Beck's Depression Inventory (BDI) After 18 Weeks
Time Frame: baseline and 18 weeks
ranging from 0 (best case) to 63 (worst case)
baseline and 18 weeks
Change From Baseline in Parkinson's Disease Sleep Scale (PDSS) After 18 Weeks
Time Frame: baseline and 18 weeks
ranging from 0 (worst case) to 150 (best case)
baseline and 18 weeks
Change From Baseline in Parkinson's Disease Quality of Life Questionnaire 39 After 18 Weeks
Time Frame: baseline and 18 weeks
Ranging from 0 (best case) to 156 (worst case)
baseline and 18 weeks
Change From Baseline in European Quality of Life (EuroQol) Scale After 18 Weeks
Time Frame: baseline and 18 weeks
ranging from 0 (worst case) to 100 (best case)
baseline and 18 weeks
Change From Baseline in 11-point Likert Scale for Pain Related to PD at Week 18
Time Frame: 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".
baseline and week 18
Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology)
Time Frame: baseline and week 18
baseline and week 18

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2007

Primary Completion (Actual)

November 1, 2008

Study Registration Dates

First Submitted

April 25, 2007

First Submitted That Met QC Criteria

April 25, 2007

First Posted (Estimate)

April 27, 2007

Study Record Updates

Last Update Posted (Estimate)

July 8, 2014

Last Update Submitted That Met QC Criteria

June 24, 2014

Last Verified

May 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 248.525

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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