Pivotal Study in Advanced Parkinsons Disease Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00466167
First received: April 25, 2007
Last updated: June 24, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Parkinson Disease
Drug: Pramipexol Extended Release
Drug: Pramipexol Immediate Release
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
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).

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Score at Week 18 [ Time Frame: baseline and week 18 ] [ Designated as safety issue: No ]
    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:
  • Change From Baseline in Percentage Off-time at Week 18 [ Time Frame: baseline and week 18 ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline and week 18 ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline and week 18 ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline and week 18 ] [ Designated as safety issue: No ]
    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 [ Time Frame: after 18 weeks of treatment ] [ Designated as safety issue: No ]
    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) [ Time Frame: after 18 weeks of treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline and 18 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline and 18 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline and 18 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline and 18 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline and 18 weeks ] [ Designated as safety issue: No ]
    ranging from 0 (best case) to 63 (worst case)

  • Change From Baseline in Parkinson's Disease Sleep Scale (PDSS) After 18 Weeks [ Time Frame: baseline and 18 weeks ] [ Designated as safety issue: No ]
    ranging from 0 (worst case) to 150 (best case)

  • Change From Baseline in Parkinson's Disease Quality of Life Questionnaire 39 After 18 Weeks [ Time Frame: baseline and 18 weeks ] [ Designated as safety issue: No ]
    Ranging from 0 (best case) to 156 (worst case)

  • Change From Baseline in European Quality of Life (EuroQol) Scale After 18 Weeks [ Time Frame: baseline and 18 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline and week 18 ] [ Designated as safety issue: No ]
    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) [ Time Frame: baseline and week 18 ] [ Designated as safety issue: No ]

Enrollment: 517
Study Start Date: April 2007
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Pramipexole ER Drug: Pramipexol Extended Release
Pramipexole IR Drug: Pramipexol Immediate Release
Placebo Comparator: Placebo Drug: Placebo

  Eligibility

Ages Eligible for Study:   32 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00466167

  Show 76 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00466167     History of Changes
Other Study ID Numbers: 248.525
Study First Received: April 25, 2007
Results First Received: November 17, 2009
Last Updated: June 24, 2014
Health Authority: Austria: Federal Office for Safety in Health Care
Czech Republic: SUKL (state institute for drug control)
Great Britain: MHRA
Hungary: National Institute of Pharmacy, H-1051 Budapest
India: Drug Control General of India
Italy: Comitato di Bioetica Az. Policlinico di Catania - CATANIA
Korea, Republic of: Korea Food and Drug Administration (KFDA)
Philippines: Department of Health, Republic of the Philippines
Poland: Registration Medicinal Product Medical Device Biocidal Product
Russia: Ministry of Healthcare and Social Development of Russian Federation, Moscow
Slovakia: SUKL (state institute for drug control), SK-825 08 Bratislava 26
Spain: Spanish Agency for Medicines and Health Products
Sweden: Regional Ethics Committee of Stockholm, PO Box 289, SE-17177 Stockholm, Sweden. Medical Products Agency, PO Box 26, SE-751 03 Uppsala, Sweden
Ukraine: Ministry of Health Care of Ukraine (MoH of Ukraine)

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Pramipexol
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on July 28, 2014