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

Parkinson Disease Clinical Trial

Official title:

Long-term Safety Study of Open-label Pramipexole Extended Release (ER) in Patients With Advanced Parkinson's Disease (PD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00577460
• Other study ID #: 248.634
• Secondary ID: 2007-004235-37
• Status: Completed
• Phase: Phase 3
• First received: December 19, 2007
• Last updated: May 7, 2014
• Start date: December 2007

Study information

• Verified date: April 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Bundesamt für Sicherheit im Gesundheitswesen, A-1030 ViennaCzech Republic: State Institute for Drug Control (SUKL), CZ-100 41 Prague 10Great Britain: MHRAHungary: National Institute of Pharmacy, H-1051 BudapestIndia: Drug Control General of IndiaItaly: Comitato di Bioetica Az. Policlinico di Catania - CATANIAKorea, Republic of: Korea Food and Drug Administration (KFDA)Philippines: Department of Health, Republic of PhillippinesPoland: Registration Medicinal Product Medical Device Biocidal ProductRussia: Ministry of Healthcare and Social Development of Russian Federation, MoscowSlovakia: SUKL (state institute for drug control), SK-825 08 Bratislava 26Spain: Spanish Agency for Medicines and Health ProductsSweden: Regional Ethics Committee of Stockholm, PO Box 289, SE-17177 Stockholm, Sweden. Medical Products Agency, PO Box 26, SE-751 03 Uppsala, SwedenUkraine: Ministry of Health Care of Ukraine (MoH of Ukraine)
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 391
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 32 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• Pramipexole
Pramipexole ER 0.375 -4.5 mg
• Placebo
Placebo tablets identical to Pramipexole ER tablets

Locations

Country	Name	City	State
Austria	248.634.43005 Boehringer Ingelheim Investigational Site	Linz
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
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
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
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
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	248.634.82003 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
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
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
Russian Federation	248.634.07001 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	248.634.07002 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	248.634.07003 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	248.634.07004 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	248.634.07007 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	248.634.07006 Boehringer Ingelheim Investigational Site	St. Petersburg
Slovakia	248.634.42104 Boehringer Ingelheim Investigational Site	Bratislava
Slovakia	248.634.42105 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
Spain	248.634.34001 Boehringer Ingelheim Investigational Site	Alcorcon (Madrid)
Spain	248.634.34003 Boehringer Ingelheim Investigational Site	Barcelona
Spain	248.634.34004 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)
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
Ukraine	248.634.38003 Boehringer Ingelheim Investigational Site	Dnipropetrovsk
Ukraine	248.634.38006 Boehringer Ingelheim Investigational Site	Kharkiv
Ukraine	248.634.38002 Boehringer Ingelheim Investigational Site	Kiev
Ukraine	248.634.38004 Boehringer Ingelheim Investigational Site	Kiev
Ukraine	248.634.38005 Boehringer Ingelheim Investigational Site	Zaporizhzhya
Ukraine	248.634.38001 Boehringer Ingelheim Investigational Site	Zaporozhye
United Kingdom	248.634.44007 Boehringer Ingelheim Investigational Site	Blackburn
United Kingdom	248.634.44003 Boehringer Ingelheim Investigational Site	Salford

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Austria,  Czech Republic,  Hungary,  India,  Italy,  Korea, Republic of,  Philippines,  Poland,  Russian Federation,  Slovakia,  Spain,  Sweden,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Patients With Adverse Events, Adverse Drug Reactions, Serious Adverse Events	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.	80 weeks	No
Secondary	Patients Successfully Switched From Pramipexole (PPX) IR or ER to ER Assessed on UPDRS II+III	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	One week	No
Secondary	UPDRS II+III Change From Open Label (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	OL Baseline and week 80	No
Secondary	Number of Participants With UPDRS II+III Response	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	Week 80	No
Secondary	Number of Patients Successfully Switched From PPX IR or ER to ER Assessed on Off-time	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).	One week	No
Secondary	Percentage Off Time During Waking Hours Total Score: Change From Baseline	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	Baseline and week 80	No
Secondary	Number of Participants With Response in Percentage Off Time During Waking Hours	Response means >=20% improvement relative to OL baseline in the % off-time during waking hours	80 weeks	No
Secondary	Percentage on Time Without Dyskinesia During Waking Hours: Change From Baseline After 80 Weeks	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.	Baseline and week 80	No
Secondary	Percentage on Time With Non Troublesome Dyskinesia During Waking Hours: Change From Baseline After 80 Weeks	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	Baseline and week 80	No
Secondary	Percentage on Time Without Dyskinesia or With Non Troublesome Dyskinesia During Waking Hours: Change From Baseline After 80 Weeks	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	Baseline and week 80	No
Secondary	Percentage on Time With Troublesome Dyskinesia During Waking Hours: Change From Baseline After 80 Weeks	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	Baseline and week 80	No
Secondary	Number of Participants With Response in CGI-I	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	32 weeks	No
Secondary	Number of Participants With Response in PGI-I	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	32 weeks	No
Secondary	Number of Participants With Response in PGI-I for Early Morning Off Symptoms	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	32 weeks	No
Secondary	UPDRS I Total Score and Change From OL Baseline at Week 80	UPDRS I ranging from 0 (normal) to 16 (severe). UPDRS I measures Mentation, Behavior and Mood	OL baseline and week 80	No
Secondary	UPDRS II Total Score and Change From OL Baseline at Week 80	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	OL baseline and week 80	No
Secondary	UPDRS III Total Score and Change From OL Baseline at Week 80	UPDRS III ranging from 0 (normal) to 108 (severe). UPDRS part III measures motor symptoms	OL baseline and week 80	No
Secondary	UPDRS IV Total Score and Change From OL Baseline at Week 80	UPDRS IV ranging from 0 (normal) to 23 (severe). UPDRS IV measures complications of therapy	OL baseline and week 80	No
Secondary	Parkinson Fatigue Scale (PFS-16) Score and Change From OL Baseline at Week 80	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	OL baseline and week 80	No
Secondary	Number of Participants With L-dopa Daily Dose Change: Change From OL Baseline at Week 80		OL baseline and week 80	No
Secondary	Number of Participants With Changes in Pramipexole Doses After 80 Weeks Compared to Pramipexole Dose at OL Baseline		OL baseline and week 80	No
Secondary	Number of Participants With Serious Adverse Events		80 weeks	No
Secondary	Supine Diastolic Blood Pressure, Baseline and Week 80, Vital Signs Treated Set		OL Baseline and Week 80	No
Secondary	Standing Diastolic Blood Pressure, Baseline and Week 80, Vital Signs Treated Set		OL Baseline and Week 80	No
Secondary	Supine Systolic Blood Pressure, Baseline and Week 80, Vital Signs Treated Set		OL Baseline and Week 80	No
Secondary	Standing Systolic Blood Pressure, Baseline and Week 80, Vital Signs Treated Set		OL Baseline and Week 80	No
Secondary	Supine Pulse Rate, Baseline and Week 80, Vital Signs Treated Set		OL Baseline and Week 80	No
Secondary	Standing Pulse Rate, Baseline and Week 80, Vital Signs Treated Set		OL Baseline and Week 80	No
Secondary	Body Weight of Female Patients, Baseline and Week 80, Vital Signs Treated Set		OL Baseline and Week 80	No
Secondary	Body Weight of Male Patients, Baseline and Week 80, Vital Signs Treated Set		OL Baseline and Week 80	No
Secondary	Epworth Sleepiness Scale (ESS), Baseline and End of Open Label, Treated Set	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)	OL Baseline and Week 80	No
Secondary	Modified Minnesota Impulsive Disorder Interview (mMIDI), Frequency of Patients With at Least One Abnormal Behavior, Treated Set	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.	Baseline, 80 weeks	No

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