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

Purpose

The general aim of this study is to obtain long-term safety and tolerability data on pramipexole extendec 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:

Genetics Home Reference related topics: Parkinson disease Perry syndrome

MedlinePlus related topics: Parkinson's Disease

Drug Information available for: Pramipexole dihydrochloride Pramipexole

U.S. FDA Resources

Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

Primary Outcome Measures:

Percentage of Patients With Adverse Events, Adverse Drug Reactions, Serious Adverse Events [ Time Frame: 80 weeks ] [ Designated as safety issue: Yes ]
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 PD (248.525 (NCT00466167)). Therefore these items were considered as a safety evaluation.

Secondary Outcome Measures:

Patients Successfully Switched From 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
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
Patients Successfully Switched From PPX IR or ER to ER Assessed on Off-time [ Time Frame: One week ] [ Designated as safety issue: No ]
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
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
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
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
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
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
L-dopa Daily Dose: Change From OL Baseline at Week 80 [ Time Frame: OL baseline and week 80 ] [ Designated as safety issue: No ]
Pramipexole Doses After 80 Weeks Compared to Pramipexole Dose at OL Baseline [ Time Frame: OL baseline and week 80 ] [ Designated as safety issue: No ]
Patients With Serious Adverse Events [ Time Frame: 80 weeks ] [ Designated as safety issue: No ]

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:

Completion of the double-blind trial 248.525
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.
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.
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:

Patients prematurely withdrawn from the double-blind trial 248.525
Atypical parkinsonian syndromes due to drugs, metabolic disorders, encephalitis or degenerative diseases
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
History of psychosis, except history of drug induced hallucinations
History of deep brain stimulation
Clinically significant ECG abnormalities at baseline
Clinically significant hypotension and/or symptomatic orthostatic hypotension at baseline
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
Serum levels of aspartate transaminase (AST) (serum glutamic oxaloacetic transaminase (SGOT)), alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase) (SGPT)), alcaline phosphatase (AP) or bilirubin > 2 upper limit nurmal (ULN) at baseline
Patients with a creatinine clearance < 50 mL/min at baseline
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
Known hypersensitivity to pramipexole or its excipients
Drug abuse, according to investigators judgement, within 2 years prior to baseline
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00577460

Show 70 Study Locations

Sponsors and Collaborators

Boehringer Ingelheim Pharmaceuticals

Investigators

Study Chair:

Boehringer Ingelheim

Boehringer Ingelheim Pharmaceuticals

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Boehringer Ingelheim, Study Chair, 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:	July 10, 2012
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
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 May 23, 2013