Pivotal Study in Advanced Parkinsons Disease Patients

Parkinson Disease Clinical Trial

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00466167
• Other study ID #: 248.525
• Status: Completed
• Phase: Phase 3
• First received: April 25, 2007
• Last updated: June 24, 2014
• Start date: April 2007

Study information

• Verified date: May 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Office for Safety in Health CareCzech Republic: SUKL (state institute for drug control)Great 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 the PhilippinesPoland: 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 517
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 32 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• Pramipexol Extended Release

• Pramipexol Immediate Release

• Placebo

Locations

Country	Name	City	State
Austria	248.525.43005 Boehringer Ingelheim Investigational Site	Linz
Czech Republic	248.525.42003 Boehringer Ingelheim Investigational Site	Pardubice
Czech Republic	248.525.42001 Boehringer Ingelheim Investigational Site	Praha
Czech Republic	248.525.42005 Boehringer Ingelheim Investigational Site	Rakovnik
Czech Republic	248.525.42002 Boehringer Ingelheim Investigational Site	Rychnov nad Kneznou
Czech Republic	248.525.42004 Boehringer Ingelheim Investigational Site	Valasske Mezirici
Hungary	248.525.36005 Boehringer Ingelheim Investigational Site	Györ
Hungary	248.525.36003 Boehringer Ingelheim Investigational Site	Kecskemét
Hungary	248.525.36006 Boehringer Ingelheim Investigational Site	Szeged
Hungary	248.525.36004 Boehringer Ingelheim Investigational Site	Veszprem
India	248.525.91004 National Institute of Mental Health & Neuro Sciences	Bangalore
India	248.525.91002 Apollo Hospital	Chennai
India	248.525.91001 Institute of Human Behaviour & Allied Sciences	Delhi
India	248.525.91003 Nizam's Institute of Medical Sciences	Hyderabad
India	248.525.91007 Boehringer Ingelheim Investigational Site	Indore
India	248.525.91005 Mallikatta Neuro Research Center	Karnataka
India	248.525.91006 King Edward Memorial Hospital & Research Centre	Pune
Italy	248.525.39001 Policlinico di Catania	Catania
Italy	248.525.39010 Campus Universitario Germaneto	Catanzaro
Italy	248.525.39009 Ce.S.I.	Chieti
Italy	248.525.39007 Ospedale della Misericordia	Grosseto
Italy	248.525.39002 Università Federico II	Napoli
Italy	248.525.39008 Azienda Ospedaliera Pisana- Università degli Studi di Pisa	Pisa
Italy	248.525.39005 Università La Sapienza di Roma	Roma
Italy	248.525.39011 Policlinico Tor Vergata	Roma
Korea, Republic of	248.525.82001 Boehringer Ingelheim Investigational Site	Gyeonggi-do
Korea, Republic of	248.525.82008 Boehringer Ingelheim Investigational Site	Kyeonggi-do
Korea, Republic of	248.525.82007 Boehringer Ingelheim Investigational Site	Pusan
Korea, Republic of	248.525.82002 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	248.525.82003 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	248.525.82004 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	248.525.82005 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	248.525.82006 Boehringer Ingelheim Investigational Site	Seoul
Philippines	248.525.63210 Makati Medical Center	Makati City
Philippines	248.525.63202 Chinese General Hospital	Manila
Philippines	248.525.63205 Jose Reyes Memorial Medical Center	Manila
Philippines	248.525.63206 Metropolitan Medical Center	Manila
Philippines	248.525.63207 Manila Doctors Hospital	Manila
Philippines	248.525.63201 The Medical City	Pasig
Philippines	248.525.63204 St Lukes Medical Center	Quezon
Philippines	248.525.63208 University of the East Ramon Magsaysay Memorial Medical Ctr	Quezon
Poland	248.525.48001 Boehringer Ingelheim Investigational Site	Gdansk
Poland	248.525.48003 Boehringer Ingelheim Investigational Site	Krakow
Poland	248.525.48002 Wolski Hospital Dr. Anna Gostynska	Warsaw
Russian Federation	248.525.07001 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	248.525.07002 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	248.525.07003 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	248.525.07004 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	248.525.07007 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	248.525.07005 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	248.525.07006 Boehringer Ingelheim Investigational Site	St. Petersburg
Slovakia	248.525.42104 Boehringer Ingelheim Investigational Site	Bratislava
Slovakia	248.525.42105 Boehringer Ingelheim Investigational Site	Bratislava
Slovakia	248.525.42103 Boehringer Ingelheim Investigational Site	Dubnica nad Vahom
Slovakia	248.525.42101 Boehringer Ingelheim Investigational Site	Trnava
Spain	248.525.34001 Boehringer Ingelheim Investigational Site	Alcorcon (Madrid)
Spain	248.525.34003 Boehringer Ingelheim Investigational Site	Barcelona
Spain	248.525.34004 Boehringer Ingelheim Investigational Site	Barcelona
Spain	248.525.34005 Boehringer Ingelheim Investigational Site	Madrid
Spain	248.525.34002 Boehringer Ingelheim Investigational Site	San Cugat del Valles (Barcelona)
Spain	248.525.34008 Boehringer Ingelheim Investigational Site	Tarrasa (Barcelona)
Sweden	248.525.46005 Boehringer Ingelheim Investigational Site	Malmö
Sweden	248.525.46002 Boehringer Ingelheim Investigational Site	Nyköping
Sweden	248.525.46001 Boehringer Ingelheim Investigational Site	Stockholm
Sweden	248.525.46004 Boehringer Ingelheim Investigational Site	Stockholm
Ukraine	248.525.38003 Boehringer Ingelheim Investigational Site	Dnipropetrovsk
Ukraine	248.525.38006 Boehringer Ingelheim Investigational Site	Kharkiv
Ukraine	248.525.38002 Boehringer Ingelheim Investigational Site	Kiev
Ukraine	248.525.38004 Boehringer Ingelheim Investigational Site	Kiev
Ukraine	248.525.38005 Boehringer Ingelheim Investigational Site	Zaporizhzhya
Ukraine	248.525.38001 Boehringer Ingelheim Investigational Site	Zaporozhye
United Kingdom	248.525.44005 Boehringer Ingelheim Investigational Site	Barnsley
United Kingdom	248.525.44007 Boehringer Ingelheim Investigational Site	Blackburn
United Kingdom	248.525.44002 Boehringer Ingelheim Investigational Site	London
United Kingdom	248.525.44004 Boehringer Ingelheim Investigational Site	Norwich
United Kingdom	248.525.44003 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	Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Score at Week 18	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	baseline and week 18	No
Secondary	Change From Baseline in Percentage Off-time at Week 18	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).	baseline and week 18	No
Secondary	Change From Baseline in Percentage On-time Without Dyskinesia at Week 18	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.	baseline and week 18	No
Secondary	Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia at Week 18	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.	baseline and week 18	No
Secondary	Change From Baseline in Percentage On-time With Troublesome Dyskinesia at Week 18	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.	baseline and week 18	No
Secondary	Clinical Global Impression - Global Improvement (CGI-I) Responder	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)	after 18 weeks of treatment	No
Secondary	Response in Patient Global Impression (PGI-I)	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)	after 18 weeks of treatment	No
Secondary	Change From Baseline in UPDRS I Score After 18 Weeks	UPDRS I ranging from 0 (normal) to 16 (severe). UPDRS I measures Mentation, Behavior and Mood	baseline and 18 weeks	No
Secondary	Change From Baseline in UPDRS II Score After 18 Weeks, Average at on and Off-period	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.	baseline and 18 weeks	No
Secondary	Change From Baseline in UPDRS III Score After 18 Weeks	UPDRS III ranging from 0 (normal) to 108 (severe). UPDRS part III measures motor symptoms	baseline and 18 weeks	No
Secondary	Change From Baseline in UPDRS IV Score After 18 Weeks	UPDRS IV ranging from 0 (normal) to 23 (severe). UPDRS IV measures complications of therapy	baseline and 18 weeks	No
Secondary	Change From Baseline in Beck's Depression Inventory (BDI) After 18 Weeks	ranging from 0 (best case) to 63 (worst case)	baseline and 18 weeks	No
Secondary	Change From Baseline in Parkinson's Disease Sleep Scale (PDSS) After 18 Weeks	ranging from 0 (worst case) to 150 (best case)	baseline and 18 weeks	No
Secondary	Change From Baseline in Parkinson's Disease Quality of Life Questionnaire 39 After 18 Weeks	Ranging from 0 (best case) to 156 (worst case)	baseline and 18 weeks	No
Secondary	Change From Baseline in European Quality of Life (EuroQol) Scale After 18 Weeks	ranging from 0 (worst case) to 100 (best case)	baseline and 18 weeks	No
Secondary	Change From Baseline in 11-point Likert Scale for Pain Related to PD at Week 18	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".	baseline and week 18	No
Secondary	Clinically Significant Abnormalities: Clinical Laboratory Evaluations (Biochemistry and Haematology)		baseline and week 18	No

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