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

Parkinson Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00601523
• Other study ID #: 248.633
• Secondary ID: 2007-004234-16
• Status: Completed
• Phase: Phase 3
• First received: January 15, 2008
• Last updated: June 3, 2014
• Start date: January 2008

Study information

• Verified date: March 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Office for Safety in Health CareCzech Republic: State Institute for Drug Control (SUKL), CZ-100 41 Prague 10Finland: Finnish Medicines AgencyFrance: Agence Française de Securite Sanitaire des Produits de SanteGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of Pharmacy, H-1051 BudapestIndia: Drug Control General of IndiaJapan: Ministry of Health, Labor and WelfareMalaysia: Ministryof Health, MalaysiaNetherlands: Central Committee on Research Involving Human Subjects (CCMO)Russia: Ministry of Healthcare and Social Development of Russian Federation, MoscowSlovakia: SUKL (state institute for drug control), SK-825 08 Bratislava 26Taiwan: Department of Health, Executive Yuan, TaiwanUkraine: Ministry of Health Care of Ukraine (MoH of Ukraine)United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The general aim of this study is to obtain long-term safety and tolerability data on pramipexole ER, in daily doses from 0.375mg to 4.5mg once daily (q.d), in patients who have previously completed a pramipexole double-blind study in early PD (248.524(NCT00479401) or 248.636(NCT00558025) trial).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 511
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years and older

Eligibility

Inclusion criteria:

1. Completion of the double-blind trial 248.524 or 248.636

2. Male or female patient with early idiopathic Parkinson´s disease (PD), and with a Modified Hoehn and Yahr stage of I to III.

3. Patient willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

4. Signed informed consent obtained before any study procedures are carried out (in accordance with International Conference on Harmonisation (ICH) - Good Clinical Practice (GCP) guidelines and local legislation).

Exclusion criteria:

1. Patients prematurely withdrawn from the double-blind trials 248.524 or 248.636.

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, fourth edition (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. Clinically significant electrocardiogram (ECG) abnormalities at baseline. 6.Clinically significant hypotension 7.Malignant melanoma or history of previously treated malignant melanoma. 8.Any other clinically significant disease, that could put the patient at risk or could prevent compliance or completion of the study. 9. Pregnancy or breast-feeding.

10. Sexually active female of childbearing potential not using a medically approved method of birth control for at least one month prior to the baseline and throughout the study.11 Serum levels of aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT), alkaline phosphatase or bilirubin > 2 upper limit of normal (ULN) at baseline 12. Patients with a creatinine clearance < 50 mL/min (estimated by the Cockcroft and Gault formula). 13. Motor complications under levodopa therapy (e.g. on-off phenomena, dyskinesia) at baseline.

14. Any medication (including intra-muscular formulations) 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: methylphenidate, cinnarizine, amphetamines. 16. Flunarizine within 3 months prior to baseline.

17. Known hypersensitivity to pramipexole or its excipients. 18. Drug abuse (including alcohol), according to investigator´s judgement, within 2 years prior to baseline.

19. Participation in investigational drug studies other than trials 248.524 and 248.636 or use of other investigational drug within one month or five times the half-life of the investigational drug 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:
• Placebo
Patient to receive placebo tablets identical to Pramipexole ER tablets. Only during transfer phase.
• Pramipexole
ER 0.375-4,5 mg

Locations

Country	Name	City	State
Austria	248.633.43001 Boehringer Ingelheim Investigational Site	Innsbruck
Austria	248.633.43004 Boehringer Ingelheim Investigational Site	Wien
Czech Republic	248.633.42004 Boehringer Ingelheim Investigational Site	Olomouc
Czech Republic	248.633.42003 Boehringer Ingelheim Investigational Site	Pardubice
Czech Republic	248.633.42001 Boehringer Ingelheim Investigational Site	Praha
Czech Republic	248.633.42002 Boehringer Ingelheim Investigational Site	Rychnov nad Kneznou
Finland	248.633.35803 Boehringer Ingelheim Investigational Site	Hyvinkää
Finland	248.633.35801 Boehringer Ingelheim Investigational Site	Oulu
Finland	248.633.35802 Boehringer Ingelheim Investigational Site	Tampere
France	248.633.3303A Boehringer Ingelheim Investigational Site	Aix en Provence
France	248.633.3303B Boehringer Ingelheim Investigational Site	Aix en Provence
France	248.633.3303C Boehringer Ingelheim Investigational Site	Aix en Provence
France	248.633.3309A Boehringer Ingelheim Investigational Site	Clermont Ferrand
France	248.633.3309B Boehringer Ingelheim Investigational Site	Clermont Ferrand
France	248.633.3305A Boehringer Ingelheim Investigational Site	Créteil
France	248.633.3305B Boehringer Ingelheim Investigational Site	Créteil
France	248.633.3313A Boehringer Ingelheim Investigational Site	Dijon cedex
France	248.633.3304A Boehringer Ingelheim Investigational Site	Evreux
France	248.633.3308A Boehringer Ingelheim Investigational Site	Lille cedex
France	248.633.3308B Boehringer Ingelheim Investigational Site	Lille cedex
France	248.633.3308C Boehringer Ingelheim Investigational Site	Lille cedex
France	248.633.3308D Boehringer Ingelheim Investigational Site	Lille cedex
France	248.633.3308E Boehringer Ingelheim Investigational Site	Lille cedex
France	248.633.3302A Boehringer Ingelheim Investigational Site	Marseille cedex 5
France	248.633.3302B Boehringer Ingelheim Investigational Site	Marseille cedex 5
France	248.633.3302C Boehringer Ingelheim Investigational Site	Marseille cedex 5
France	248.633.3306B Boehringer Ingelheim Investigational Site	Montpellier
France	248.633.3306C Boehringer Ingelheim Investigational Site	Montpellier
France	248.633.3306D Boehringer Ingelheim Investigational Site	Montpellier
France	248.633.3306F Boehringer Ingelheim Investigational Site	Montpellier
France	248.633.3306A Boehringer Ingelheim Investigational Site	Montpellier cédex 5
France	248.633.3312A Boehringer Ingelheim Investigational Site	Rouen
France	248.633.3312B Boehringer Ingelheim Investigational Site	Rouen
France	248.633.3311A Boehringer Ingelheim Investigational Site	Strasbourg
France	248.633.3311B Boehringer Ingelheim Investigational Site	Strasbourg
France	248.633.3301A Boehringer Ingelheim Investigational Site	Toulouse
France	248.633.3301D Boehringer Ingelheim Investigational Site	Toulouse
France	248.633.3301F Boehringer Ingelheim Investigational Site	Toulouse
France	248.633.3301G Boehringer Ingelheim Investigational Site	Toulouse
France	248.633.3301B Boehringer Ingelheim Investigational Site	Toulouse cedex
France	248.633.3301C Boehringer Ingelheim Investigational Site	Toulouse Cedex 7
Germany	248.633.49009 Boehringer Ingelheim Investigational Site	Achim bei Bremen
Germany	248.633.49002 Boehringer Ingelheim Investigational Site	Berlin
Germany	248.633.49004 Boehringer Ingelheim Investigational Site	Berlin
Germany	248.633.49018 Boehringer Ingelheim Investigational Site	Berlin
Germany	248.633.49019 Boehringer Ingelheim Investigational Site	Berlin
Germany	248.633.49003 Boehringer Ingelheim Investigational Site	Berlin-Steglitz
Germany	248.633.49005 Boehringer Ingelheim Investigational Site	Bochum
Germany	248.633.49016 Boehringer Ingelheim Investigational Site	Bochum
Germany	248.633.49007 Boehringer Ingelheim Investigational Site	Dresden
Germany	248.633.49011 Boehringer Ingelheim Investigational Site	Gera
Germany	248.633.49017 Boehringer Ingelheim Investigational Site	Karlsruhe
Germany	248.633.49001 Boehringer Ingelheim Investigational Site	Kassel
Germany	248.633.49012 Boehringer Ingelheim Investigational Site	Leipzig
Germany	248.633.49013 Boehringer Ingelheim Investigational Site	Marburg
Germany	248.633.49015 Boehringer Ingelheim Investigational Site	Unterhaching
Hungary	248.633.36007 Boehringer Ingelheim Investigational Site	Eger
Hungary	248.633.36005 Boehringer Ingelheim Investigational Site	Györ
Hungary	248.633.36008 Boehringer Ingelheim Investigational Site	Miskolc
Hungary	248.633.36004 Boehringer Ingelheim Investigational Site	Sopron
Hungary	248.633.36001 Boehringer Ingelheim Investigational Site	Szeged
Hungary	248.633.36006 Boehringer Ingelheim Investigational Site	Szeged
Hungary	248.633.36003 Boehringer Ingelheim Investigational Site	Szombathely
Hungary	248.633.36002 Boehringer Ingelheim Investigational Site	Zalaegerszeg
India	248.633.91002 Boehringer Ingelheim Investigational Site	Chennai
India	248.633.91009 Boehringer Ingelheim Investigational Site	Hyderabad
India	248.633.91001 Boehringer Ingelheim Investigational Site	Karnataka
India	248.633.91005 Boehringer Ingelheim Investigational Site	Maharashtra
India	248.633.91007 Boehringer Ingelheim Investigational Site	Maharashtra
India	248.633.91004 Boehringer Ingelheim Investigational Site	New Delhi
India	248.633.91011 Boehringer Ingelheim Investigational Site	Pune
Japan	248.633.81010 Boehringer Ingelheim Investigational Site	Aomori, Aomori
Japan	248.633.81001 Boehringer Ingelheim Investigational Site	Bunkyo-ku, Tokyo
Japan	248.633.81005 Boehringer Ingelheim Investigational Site	Fuchu, Tokyo
Japan	248.633.81011 Boehringer Ingelheim Investigational Site	Fujisawa, Kanagawa
Japan	248.633.81013 Boehringer Ingelheim Investigational Site	Fukuoka, Fukuoka
Japan	248.633.81015 Boehringer Ingelheim Investigational Site	Iwamizawa,Hokkaido
Japan	248.633.81003 Boehringer Ingelheim Investigational Site	Kodaira, Tokyo
Japan	248.633.81014 Boehringer Ingelheim Investigational Site	Kyoto, Kyoto
Japan	248.633.81009 Boehringer Ingelheim Investigational Site	Morioka, Iwate
Japan	248.633.81008 Boehringer Ingelheim Investigational Site	Okayama, Okayama
Japan	248.633.81006 Boehringer Ingelheim Investigational Site	Ota-ku, Tokyo
Japan	248.633.81004 Boehringer Ingelheim Investigational Site	Sagamihara, Kanagawa
Japan	248.633.81007 Boehringer Ingelheim Investigational Site	Shimogyo-ku, Kyoto, Kyoto
Japan	248.633.81012 Boehringer Ingelheim Investigational Site	Shiroishi, Miyagi
Japan	248.633.81002 Boehringer Ingelheim Investigational Site	Takamatsu, Kagawa
Malaysia	248.633.60004 Boehringer Ingelheim Investigational Site	Kuala Terengganu
Netherlands	248.633.31002 Boehringer Ingelheim Investigational Site	Geldrop
Netherlands	248.633.31003 Boehringer Ingelheim Investigational Site	Helmond
Netherlands	248.633.31006 Boehringer Ingelheim Investigational Site	Maastricht
Netherlands	248.633.31004 Boehringer Ingelheim Investigational Site	Nijmegen
Netherlands	248.633.31001 Boehringer Ingelheim Investigational Site	Sittard-geleen
Russian Federation	248.633.07001 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	248.633.07002 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	248.633.07003 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	248.633.07004 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	248.633.07006 Boehringer Ingelheim Investigational Site	St. Petersburg
Slovakia	248.633.42103 Boehringer Ingelheim Investigational Site	Dubnica nad Vahom
Slovakia	248.633.42101 Boehringer Ingelheim Investigational Site	Trnava
Taiwan	248.633.88603 Boehringer Ingelheim Investigational Site	Kaohsiung
Taiwan	248.633.88605 Boehringer Ingelheim Investigational Site	Taichung
Taiwan	248.633.88601 Boehringer Ingelheim Investigational Site	Taipei
Taiwan	248.633.88602 Boehringer Ingelheim Investigational Site	Taoyuan
Ukraine	248.633.38005 Boehringer Ingelheim Investigational Site	Kiev
Ukraine	248.633.38001 Boehringer Ingelheim Investigational Site	Lvov
Ukraine	248.633.38002 Boehringer Ingelheim Investigational Site	Uzhgorod
Ukraine	248.633.38003 Boehringer Ingelheim Investigational Site	Vinnytzya
Ukraine	248.633.38004 Boehringer Ingelheim Investigational Site	Zaporizhzhya
Ukraine	248.633.38006 Boehringer Ingelheim Investigational Site	Zaporozhye
United States	248.633.01010 Boehringer Ingelheim Investigational Site	Boca Raton	Florida
United States	248.633.01009 Boehringer Ingelheim Investigational Site	Burlington	Vermont
United States	248.633.01012 Boehringer Ingelheim Investigational Site	Chicago	Illinois
United States	248.633.01005 Boehringer Ingelheim Investigational Site	Commack	New York
United States	248.633.01008 Boehringer Ingelheim Investigational Site	Danbury	Connecticut
United States	248.633.01001 Boehringer Ingelheim Investigational Site	Kansas City	Kansas
United States	248.633.01016 Boehringer Ingelheim Investigational Site	La Jolla	California
United States	248.633.01013 Boehringer Ingelheim Investigational Site	Oxnard	California
United States	248.633.01004 Boehringer Ingelheim Investigational Site	Sun City	Arizona
United States	248.633.01018 Boehringer Ingelheim Investigational Site	Tempe	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Austria,  Czech Republic,  Finland,  France,  Germany,  Hungary,  India,  Japan,  Malaysia,  Netherlands,  Russian Federation,  Slovakia,  Taiwan,  Ukraine, 

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 early PD (248.524 (NCT00479401) or 248.636 (NCT00558025)). Therefore these items were considered as a safety evaluation	80 weeks (patients from 248.524) or 72 weeks (patients from 248.636)	No
Secondary	Unified Parkinson's Disease Rating Scale (UPDRS) II+III Total Score: Change 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	Open Label (OL) baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636)	No
Secondary	Number of Patients With UPDRS II+III Response From OL Baseline at Week 80 (Patients From 248.524) or Week 72 (Patients From 248.636)	A response means an improvement of >=20% 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	OL Baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636)	No
Secondary	UPDRS I Total Score: Change From OL Baseline	UPDRS I ranging from 0 (normal) to 16 (severe), measures Mentation, Behavior and Mood	OL baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636)	No
Secondary	UPDRS II Total Score: Change From OL Baseline	UPDRS II ranging from 0 (normal) to 52 (severe), measures activity of daily living.	OL baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636)	No
Secondary	UPDRS III Total Score: Change From OL Baseline	UPDRS III ranging from 0 (normal) to 108 (severe) measures motor symptoms	OL baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636)	No
Secondary	Response in Clinical Global Impression of Improvement (CGI-I)	Clinicians evaluation in a rating scale of 7 steps, 1 meaning very much improved to 7 meaning 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 Pramipexole ER or Immediate Release (IR), all patients with no change to very much improved were considered as responders	OL Baseline and week 32 (patients from 248.524) or week 24 (patients from 248.636)	No
Secondary	Response in Patient Global Impression of Improvement (PGI-I)	Patient rated evaluation of the PD symptoms on a rating scale of 7 steps, 1 meaning very much better to 7 meaning 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 pramipexole (PPX) ER or IR, all patients with no change to very much better were considered as responders	OL Baseline and week 32 (patients from 248.524) or week 24 (patients from 248.636)	No
Secondary	Parkinson Fatigue Scale (PFS-16) : Change From OL Baseline	PFS-16 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 (patients from 248.524) or week 72 (patients from 248.636)	No
Secondary	Number of Patients Introducing L-Dopa Medication in OL Trial	Number of patients requiring Levodopa supplementation during the study	80 weeks (patients from 248.524) or 72 weeks (patients from 248.636)	No
Secondary	L-Dopa Dose: Change From OL Baseline	Change from open-label baseline in Levodopa dose	OL baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636)	No
Secondary	Pramipexole Doses Respectively After 80 Weeks Compared to Pramipexole Doses at Week 8 for Previously 248.524 Patients and After 72 Weeks Compared to Pramipexole Doses at Week 0 for Previously 248.636 Patients	Change from open-label baseline in Levodopa dose over the final 72 weeks of open-label assessment	Week 8 and week 80 (patients from 248.524) or week 0 and week 72 (patients from 248.636)	No
Secondary	Patient Preference Regarding Treatment Dosing	Patients were surveyed on their preference for Once Daily dosing versus Three Times Daily dosing	80 weeks (patients from 248.524) or 72 weeks (patients from 248.636)	No
Secondary	Patient Rating of Convenience of Treatment Dosing	Patients were surveyed on the convenience of Once Daily dosing versus Three Times Daily dosing	80 weeks (patients from 248.524) or 72 weeks (patients from 248.636)	No

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