Long-term Safety Study of Open-label Pramipexole ER in Patients With Advanced PD

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00577460
First received: December 19, 2007
Last updated: May 7, 2014
Last verified: April 2014
  Purpose

The general aim of this study is to obtain long-term safety and tolerability data on pramipexole extended release (ER), in daily doses from 0.375mg to 4.5mg once daily (qd), in patients who have previously completed a pramipexole double-blind study in advanced Parkinson's disease (PD) (248.525 trial).


Condition Intervention Phase
Parkinson Disease
Drug: Pramipexole
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Long-term Safety Study of Open-label Pramipexole Extended Release (ER) in Patients With Advanced Parkinson's Disease (PD)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Percentage of Patients With Adverse Events, Adverse Drug Reactions, Serious Adverse Events [ Time Frame: 80 weeks ] [ Designated as safety issue: No ]
    The aim of this study was to obtain long-term safety and tolerability data on pramipexole ER, in patients who have previously completed a pramipexole double blind study in advanced Parkinson's Disease (PD) (248.525 (NCT00466167)). Therefore these items were considered as a safety evaluation.


Secondary Outcome Measures:
  • Patients Successfully Switched From Pramipexole (PPX) IR or ER to ER Assessed on UPDRS II+III [ Time Frame: One week ] [ Designated as safety issue: No ]
    Unified Parkinson's Disease Rating Scale (UPDRS) Successfully switched means: UPDRS II+III baseline score >20 without a relative worsening of UPDRS II+III score > 15% from baseline or UPDRS II+III baseline score <=20 without an absolute worsening of UPDRS II+III score > 3 from baseline UPDRS II+III ranging from 0 (normal) to 160 (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms

  • UPDRS II+III Change From Open Label (OL) Baseline [ Time Frame: OL Baseline and week 80 ] [ Designated as safety issue: No ]
    UPDRS II+III ranging from 0 (normal) to 160 (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms

  • Number of Participants With UPDRS II+III Response [ Time Frame: Week 80 ] [ Designated as safety issue: No ]
    A response means an improvement of >=20% in UPDRS II+III from OL baseline UPDRS II+III ranging from 0 (normal) to 160 (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms

  • Number of Patients Successfully Switched From PPX IR or ER to ER Assessed on Off-time [ Time Frame: One week ] [ Designated as safety issue: No ]
    A patient was considered as successfully switched if he/she has converted to ER without a worsening of off time by more than 12.5% from baseline. Off-time is based on patient diary data and describes a period when the patient experiences increased parkinsonian symptoms (e.g. immobility or inability to move with ease).

  • Percentage Off Time During Waking Hours Total Score: Change From Baseline [ Time Frame: Baseline and week 80 ] [ 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).

    A negative change implies improvement


  • Number of Participants With Response in Percentage Off Time During Waking Hours [ Time Frame: 80 weeks ] [ Designated as safety issue: No ]
    Response means >=20% improvement relative to OL baseline in the % off-time during waking hours

  • Percentage on Time Without Dyskinesia During Waking Hours: Change From Baseline After 80 Weeks [ Time Frame: Baseline and week 80 ] [ 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. A positive change implies improvement.

  • Percentage on Time With Non Troublesome Dyskinesia During Waking Hours: Change From Baseline After 80 Weeks [ Time Frame: Baseline and week 80 ] [ 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. A positive change implies improvement

  • Percentage on Time Without Dyskinesia or With Non Troublesome Dyskinesia During Waking Hours: Change From Baseline After 80 Weeks [ Time Frame: Baseline and week 80 ] [ Designated as safety issue: No ]
    Percentage on-time without dyskinesia or 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. A positive change implies improvement

  • Percentage on Time With Troublesome Dyskinesia During Waking Hours: Change From Baseline After 80 Weeks [ Time Frame: Baseline and week 80 ] [ Designated as safety issue: No ]
    Percentage on-time with 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. A positive change implies improvement

  • Number of Participants With Response in CGI-I [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]
    Clinical Global Impression of Improvement (CGI-I), CGI-I scores ranging from '1' (very much improved) to '7' (very much worse). For patients previously treated with Placebo, all patients with at least "much improved" were considered as responders. For patients previously treated with PPX ER or IR, all patients with no change to very much improved were considered as responders

  • Number of Participants With Response in PGI-I [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]
    Patient Global Impression of Improvement (PGI-I), PGI-I scores ranging from '1' (very much better) to '7' (very much worse). For patients previously treated with Placebo, all patients with at least "much better" were considered as responders. For patients previously treated with PPX ER or IR, all patients with no change to very much better were considered as responders

  • Number of Participants With Response in PGI-I for Early Morning Off Symptoms [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]
    Patient Global Impression of Improvement (PGI-I) for early morning off symptoms, PGI-I scores ranging from '1' (very much better) to '7' (very much worse). For patients previously treated with Placebo, all patients with at least "much better" were considered as responders. For patients previously treated with PPX ER or IR, all patients with no change to very much better were considered as responders

  • UPDRS I Total Score and Change From OL Baseline at Week 80 [ Time Frame: OL baseline and week 80 ] [ Designated as safety issue: No ]
    UPDRS I ranging from 0 (normal) to 16 (severe). UPDRS I measures Mentation, Behavior and Mood

  • UPDRS II Total Score and Change From OL Baseline at Week 80 [ Time Frame: OL baseline and week 80 ] [ 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

  • UPDRS III Total Score and Change From OL Baseline at Week 80 [ Time Frame: OL baseline and week 80 ] [ Designated as safety issue: No ]
    UPDRS III ranging from 0 (normal) to 108 (severe). UPDRS part III measures motor symptoms

  • UPDRS IV Total Score and Change From OL Baseline at Week 80 [ Time Frame: OL baseline and week 80 ] [ Designated as safety issue: No ]
    UPDRS IV ranging from 0 (normal) to 23 (severe). UPDRS IV measures complications of therapy

  • Parkinson Fatigue Scale (PFS-16) Score and Change From OL Baseline at Week 80 [ Time Frame: OL baseline and week 80 ] [ Designated as safety issue: No ]
    PFS-16 (Parkinson fatigue scale) ranging from 16 (better perceived health status) to 80 (severe symptoms of the disease) measuring aspects of fatigue that are relevant to patients with PD

  • Number of Participants With L-dopa Daily Dose Change: Change From OL Baseline at Week 80 [ Time Frame: OL baseline and week 80 ] [ Designated as safety issue: No ]
  • Number of Participants With Changes in Pramipexole Doses After 80 Weeks Compared to Pramipexole Dose at OL Baseline [ Time Frame: OL baseline and week 80 ] [ Designated as safety issue: No ]
  • Number of Participants With Serious Adverse Events [ Time Frame: 80 weeks ] [ Designated as safety issue: No ]
  • Supine Diastolic Blood Pressure, Baseline and Week 80, Vital Signs Treated Set [ Time Frame: OL Baseline and Week 80 ] [ Designated as safety issue: No ]
  • Standing Diastolic Blood Pressure, Baseline and Week 80, Vital Signs Treated Set [ Time Frame: OL Baseline and Week 80 ] [ Designated as safety issue: No ]
  • Supine Systolic Blood Pressure, Baseline and Week 80, Vital Signs Treated Set [ Time Frame: OL Baseline and Week 80 ] [ Designated as safety issue: No ]
  • Standing Systolic Blood Pressure, Baseline and Week 80, Vital Signs Treated Set [ Time Frame: OL Baseline and Week 80 ] [ Designated as safety issue: No ]
  • Supine Pulse Rate, Baseline and Week 80, Vital Signs Treated Set [ Time Frame: OL Baseline and Week 80 ] [ Designated as safety issue: No ]
  • Standing Pulse Rate, Baseline and Week 80, Vital Signs Treated Set [ Time Frame: OL Baseline and Week 80 ] [ Designated as safety issue: No ]
  • Body Weight of Female Patients, Baseline and Week 80, Vital Signs Treated Set [ Time Frame: OL Baseline and Week 80 ] [ Designated as safety issue: No ]
  • Body Weight of Male Patients, Baseline and Week 80, Vital Signs Treated Set [ Time Frame: OL Baseline and Week 80 ] [ Designated as safety issue: No ]
  • Epworth Sleepiness Scale (ESS), Baseline and End of Open Label, Treated Set [ Time Frame: OL Baseline and Week 80 ] [ Designated as safety issue: No ]
    ESS Total score ranges from zero (best) to 24 (worst); scale has 8 items, each rated from zero (no chance of dozing) to 3 (high chance of dozing)

  • Modified Minnesota Impulsive Disorder Interview (mMIDI), Frequency of Patients With at Least One Abnormal Behavior, Treated Set [ Time Frame: Baseline, 80 weeks ] [ Designated as safety issue: No ]
    The mMIDI is a semi-structured interview designed to assess impulsive control disorders. The scale was modified to focus behaviors of: pathological gambling, compulsive buying and compulsive sexual behavioral.


Enrollment: 391
Study Start Date: December 2007
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Pramipexole
Patients to receive Pramipexole ER 0.375 - 4.5 mg in tablet form daily
Drug: Pramipexole
Pramipexole ER 0.375 -4.5 mg
Placebo Comparator: Placebo
Patients to receive placebo tablets identical to Pramipexole ER tablets only during transfer phase
Drug: Placebo
Placebo tablets identical to Pramipexole ER tablets

  Eligibility

Ages Eligible for Study:   32 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Completion of the double-blind trial 248.525
  2. Male or female patient with advanced idiopathic Parkinson's disease (PD), with a Modified Hoehn and Yahr stage of 2 to 4 at on-time, and a concomitant treatment with standard or controlled release L-Dopa+, or a combination of L-Dopa+ and entacapone.
  3. Patient willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. In particular the patient should be able to recognise the off-time and on-time periods during waking hours and the patient (or a family member or a guardian) should be able to record them accurately in the patient diary.
  4. Signed informed consent obtained before any study procedures are carried out (in accordance with International Conference of Harmonization - Good Clinical Practice (ICH-GCP) guidelines and local legislation).

Exclusion criteria:

  1. Patients prematurely withdrawn from the double-blind trial 248.525
  2. Atypical parkinsonian syndromes due to drugs, metabolic disorders, encephalitis or degenerative diseases
  3. Any psychiatric disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV 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 ECG abnormalities at baseline
  7. Clinically significant hypotension and/or symptomatic orthostatic hypotension at baseline
  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
  12. Serum levels of aspartate transaminase (AST) (serum glutamic oxaloacetic transaminase (SGOT)), alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase) (SGPT)), alkaline phosphatase (AP) or bilirubin > 2 upper limit normal (ULN) at baseline
  13. Patients with a creatinine clearance < 50 mL/min at baseline
  14. Any medication with central dopaminergic antagonist activity within 4 weeks prior to the baseline visit
  15. Any of the following drugs within 4 weeks prior to baseline visit: methylphenidate, cinnarizine, amphetamines
  16. Flunarizine within 3 months prior to baseline
  17. Known hypersensitivity to pramipexole or its excipients
  18. Drug abuse, according to investigators judgement, within 2 years prior to baseline
  19. Participation in investigational drug studies other than the trial 248.525, 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
  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: NCT00577460

  Hide Study Locations
Locations
Austria
248.634.43005 Boehringer Ingelheim Investigational Site
Linz, Austria
Czech Republic
248.634.42003 Boehringer Ingelheim Investigational Site
Pardubice, Czech Republic
248.634.42001 Boehringer Ingelheim Investigational Site
Praha, Czech Republic
248.634.42005 Boehringer Ingelheim Investigational Site
Rakovnik, Czech Republic
248.634.42002 Boehringer Ingelheim Investigational Site
Rychnov nad Kneznou, Czech Republic
248.634.42004 Boehringer Ingelheim Investigational Site
Valasske Mezirici, Czech Republic
Hungary
248.634.36005 Boehringer Ingelheim Investigational Site
Györ, Hungary
248.634.36003 Boehringer Ingelheim Investigational Site
Kecskemét, Hungary
248.634.36006 Boehringer Ingelheim Investigational Site
Szeged, Hungary
248.634.36004 Boehringer Ingelheim Investigational Site
Veszprem, Hungary
India
248.634.91002 Boehringer Ingelheim Investigational Site
Chennai, India
248.634.91001 Boehringer Ingelheim Investigational Site
Delhi, India
248.634.91003 Boehringer Ingelheim Investigational Site
Hyderabad, India
248.634.91007 Boehringer Ingelheim Investigational Site
Indore, India
248.634.91005 Boehringer Ingelheim Investigational Site
Karnataka, India
248.634.91006 Boehringer Ingelheim Investigational Site
Pune, India
Italy
248.634.39001 Boehringer Ingelheim Investigational Site
Catania, Italy
248.634.39010 Boehringer Ingelheim Investigational Site
Catanzaro, Italy
248.634.39009 Boehringer Ingelheim Investigational Site
Chieti, Italy
248.634.39007 Boehringer Ingelheim Investigational Site
Grosseto, Italy
248.634.39002 Boehringer Ingelheim Investigational Site
Napolii, Italy
248.634.39008 Boehringer Ingelheim Investigational Site
Pisa, Italy
248.634.39005 Boehringer Ingelheim Investigational Site
Roma, Italy
248.634.39011 Boehringer Ingelheim Investigational Site
Roma, Italy
Korea, Republic of
248.634.82001 Boehringer Ingelheim Investigational Site
Gyeonggi-do, Korea, Republic of
248.634.82008 Boehringer Ingelheim Investigational Site
Kyeonggi-do, Korea, Republic of
248.634.82007 Boehringer Ingelheim Investigational Site
Pusan, Korea, Republic of
248.634.82002 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
248.634.82004 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
248.634.82005 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
248.634.82006 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
248.634.82003 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
Philippines
248.634.63202 Boehringer Ingelheim Investigational Site
Cruz, Manila, Philippines
248.634.63207 Boehringer Ingelheim Investigational Site
Ermita, Manila, Philippines
248.634.63210 Boehringer Ingelheim Investigational Site
Makati City, Philippines
248.634.63205 Boehringer Ingelheim Investigational Site
Manila, Philippines
248.634.63206 Boehringer Ingelheim Investigational Site
Manila, Philippines
248.634.63201 Boehringer Ingelheim Investigational Site
Pasig City, Philippines
248.634.63208 Boehringer Ingelheim Investigational Site
Quezon, Philippines
248.634.63204 Boehringer Ingelheim Investigational Site
Quezon City, Philippines
Poland
248.634.48001 Boehringer Ingelheim Investigational Site
Gdansk, Poland
248.634.48003 Boehringer Ingelheim Investigational Site
Krakow, Poland
248.634.48002 Boehringer Ingelheim Investigational Site
Warsaw, Poland
Russian Federation
248.634.07001 Boehringer Ingelheim Investigational Site
Moscow, Russian Federation
248.634.07007 Boehringer Ingelheim Investigational Site
Moscow, Russian Federation
248.634.07002 Boehringer Ingelheim Investigational Site
Moscow, Russian Federation
248.634.07004 Boehringer Ingelheim Investigational Site
Moscow, Russian Federation
248.634.07003 Boehringer Ingelheim Investigational Site
Moscow, Russian Federation
248.634.07006 Boehringer Ingelheim Investigational Site
St. Petersburg, Russian Federation
Slovakia
248.634.42105 Boehringer Ingelheim Investigational Site
Bratislava, Slovakia
248.634.42104 Boehringer Ingelheim Investigational Site
Bratislava, Slovakia
248.634.42103 Boehringer Ingelheim Investigational Site
Dubnica nad Vahom, Slovakia
248.634.42101 Boehringer Ingelheim Investigational Site
Trnava, Slovakia
Spain
248.634.34001 Boehringer Ingelheim Investigational Site
Alcorcon (Madrid), Spain
248.634.34004 Boehringer Ingelheim Investigational Site
Barcelona, Spain
248.634.34003 Boehringer Ingelheim Investigational Site
Barcelona, Spain
248.634.34005 Boehringer Ingelheim Investigational Site
Madrid, Spain
248.634.34002 Boehringer Ingelheim Investigational Site
San Cugat del Valles (Barcelona), Spain
248.634.34008 Boehringer Ingelheim Investigational Site
Tarrasa (Barcelona), Spain
Sweden
248.634.46005 Boehringer Ingelheim Investigational Site
Malmö, Sweden
248.634.46002 Boehringer Ingelheim Investigational Site
Nyköping, Sweden
248.634.46001 Boehringer Ingelheim Investigational Site
Stockholm, Sweden
Ukraine
248.634.38003 Boehringer Ingelheim Investigational Site
Dnipropetrovsk, Ukraine
248.634.38006 Boehringer Ingelheim Investigational Site
Kharkiv, Ukraine
248.634.38004 Boehringer Ingelheim Investigational Site
Kiev, Ukraine
248.634.38002 Boehringer Ingelheim Investigational Site
Kiev, Ukraine
248.634.38005 Boehringer Ingelheim Investigational Site
Zaporizhzhya, Ukraine
248.634.38001 Boehringer Ingelheim Investigational Site
Zaporozhye, Ukraine
United Kingdom
248.634.44007 Boehringer Ingelheim Investigational Site
Blackburn, United Kingdom
248.634.44003 Boehringer Ingelheim Investigational Site
Salford, United Kingdom
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: NCT00577460     History of Changes
Other Study ID Numbers: 248.634, 2007-004235-37
Study First Received: December 19, 2007
Results First Received: June 16, 2011
Last Updated: May 7, 2014
Health Authority: Austria: Bundesamt für Sicherheit im Gesundheitswesen, A-1030 Vienna
Czech Republic: State Institute for Drug Control (SUKL), CZ-100 41 Prague 10
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 Phillippines
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
Pramipexole
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 October 19, 2014