Pramipexole Versus Placebo in Parkinson's Disease (PD) Patients With Depressive Symptoms

Depression Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Parallel Group Efficacy Study of Pramipexole and Placebo Administered Orally Over a 12 Week Treatment Phase in Parkinson's Disease Patients With Stable Motor Function and Depressive Symptoms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00297778
• Other study ID #: 248.596
• Secondary ID: Eudract 2005-003
• Status: Completed
• Phase: Phase 4
• First received: February 28, 2006
• Last updated: June 3, 2014
• Start date: March 2006

Study information

• Verified date: April 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Office for Safety in Health CareFinland: Finnish Medicines AgencyFrance: AfssapsGermany: Ethikkommission bei der Landesaerztekammer Baden-WuerttembergItaly: Comitato Etico Ospedale Civile S. Spirito, Università "G. D'Annunzio"Netherlands: Medish Etische toetsingscommissie Atrium MCNorway: Norwegian Medicines Agency (Statens Legemiddelverk)Romania: National Medicines Agency, BucharestRussia: Ministry of Healthcare and Social Development of Russian Federation, MoscowSouth Africa: Medicines Council CountrySpain: Unidad de Registro y Tasas, Agencia Espanola del medicamento y productos sanitariosSweden: Medical Products AgencyUkraine: Ministry of Health Care of Ukraine (MoH of Ukraine)
• Study type: Interventional

Clinical Trial Summary

Parkinsons Disease (PD) is caused by a decrease of dopamine in a particular part of the brain. Dopamine is a messenger substance (neurotransmitter) that is used by the cells of the brain (nerve cells) to control and harmonize muscle movements. Consequently, the main manifestations of the disease affect movement and include tremor, muscular rigidity, slowness in performing movements and loss of balance.

However, the disease affects also other, non motor functions and may cause other disorders, such as depression. Depression may be a reaction to the disability caused by the disease, but many studies show that depression is more common in PD than in other chronic debilitating illnesses. Moreover, there is also a biological explanation for the phenomenon: dopamine is also used in brain circuits involved in the experience of pleasure, and loss of pleasure in daily physical or social activity is one of the key manifestations of depression.

The objective of the study is to assess whether pramipexole, at doses approved for the treatment of PD symptoms, is more effective than placebo in resolving depressive symptoms in PD patients.

Also data on the safety of the product in the disease will be collected.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 296
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 80 Years

Eligibility

Inclusion Criteria:

1. 15-item Geriatric Depression Scale (GDS) > or = 5

2. Unified Parkinson's Disease Rating Scale (UPDRS) Part I Score on Question #3 > or = 2

3. Folsteins Mini-Mental State Examination (MMSE) score > 24

4. Male or female patient with PD (UK PD Brain Bank criteria).

5. Patients diagnosed with idiopathic PD, Stage I-III by the Modified Hoehn and Yahr Scale and optimally controlled PD symptoms .

6. Male or female patients aged 30 - 80 years.

7. Ability to provide written informed consent.

8. Women of childbearing potential must have a negative serum beta-humanchoriongonadotropin (Beta-HCG) pregnancy test at the Screening visit unless surgically sterile or last menstruation >or = 12 months prior to signing informed consent.

9. Women of childbearing potential must be using an accepted contraceptive.

10. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Previous history of allergic response, lack of efficacy or complications with pramipexole or its excipients.

2. History of suicidal attempts in the last twelve months; presence of suicidal tendencies/potential.

3. Atypical PD syndromes due to drugs, metabolic disorders, encephalitis or degenerative diseases.

4. History of PD stereotactic brain surgery.

5. Surgery within 180 days of randomization that would negatively impact the patients participation in the study.

6. History of active epilepsy within the past year.

7. Current psychotherapy or behavior therapy while participating the trial

8. Symptomatic orthostatic hypotension prior to randomization.

9. Malignant melanoma or history of previously treated malignant melanoma.

10. Patients who have received typical neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine, selegiline or amphetamine derivatives within the past 3 months.

11. Patients who have received dopamine agonists within the past 30 days

12. Electroconvulsive therapy during the 90 days preceding the screening visit (Visit 1).

13. Patients who are currently lactating.

14. Participation in other investigational drug studies or use of other investigational drugs within the previous 30 days prior to randomization.

15. Any other laboratory assay abnormality, which could interfere with patient participation or interpretation of results, or could increase the risk for the patient

16. Any other clinically significant medical/psychiatric condition, which could interfere with patient participation or interpretation of results, or could increase the risk for the patient

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Parkinson Disease

Intervention

Drug:
• Pramipexole
Dopamine agonist

Other:
• Placebo

Locations

Country	Name	City	State
Austria	248.596.43003 Boehringer Ingelheim Investigational Site	Graz
Austria	248.596.43001 Boehringer Ingelheim Investigational Site	Innsbruck
Austria	248.596.43005 Boehringer Ingelheim Investigational Site	Linz
Austria	248.596.43004 Boehringer Ingelheim Investigational Site	St. Pölten
Austria	248.596.43002 Boehringer Ingelheim Investigational Site	Wien
Finland	248.596.35801 Boehringer Ingelheim Investigational Site	Oulu
France	248.596.3302A Centre Hospitalier du Pays d'Aix	Aix en Provence
France	248.596.3302B Centre Hospitalier du Pays d'Aix	Aix en Provence cedex 1
France	248.596.3306A Hôpital Pierre Wertheimer	Bron cedex
France	248.596.3308A Hôpital Gabriel Montpied	Clermont Ferrand
France	248.596.3309A Cabinet Médical	Evreux
France	248.596.3307A Hôpital Roger Salengro	Lille cedex
France	248.596.3307B Hôpital Roger Salengro	Lille cedex
France	248.596.3307C Hôpital Roger Salengro	Lille cedex
France	248.596.3303A Hôpital La Timone	Marseille cedex 5
France	248.596.3305A Hôpital du Haut Levêque	Pessac cédex
France	248.596.3305B Hôpital du Haut Levêque	Pessac cédex
France	248.596.3301A Hôpital Guillaume et René Laennec	Saint Herblain
Germany	248.596.49002 Boehringer Ingelheim Investigational Site	Berlin
Germany	248.596.49013 Boehringer Ingelheim Investigational Site	Berlin
Germany	248.596.49015 Boehringer Ingelheim Investigational Site	Berlin
Germany	248.596.49012 Boehringer Ingelheim Investigational Site	Berlin-Steglitz
Germany	248.596.49003 Boehringer Ingelheim Investigational Site	Bremerhaven
Germany	248.596.49004 Boehringer Ingelheim Investigational Site	Gera
Germany	248.596.49001 Boehringer Ingelheim Investigational Site	Karlsruhe
Germany	248.596.49016 Boehringer Ingelheim Investigational Site	Köln
Germany	248.596.49005 Boehringer Ingelheim Investigational Site	Marburg
Germany	248.596.49014 Boehringer Ingelheim Investigational Site	Mittweida
Germany	248.596.49008 Boehringer Ingelheim Investigational Site	München
Italy	248.596.39008 Clinica Neurologica I Policlinico di Catania	Catania
Italy	248.596.39004 Neurologia Ospedale della Misericordia	Grosseto
Italy	248.596.39005 Clinica Neurologica Policlinico G. Martino	Messina
Italy	248.596.39009 Istituti Clinici di Perfezionamento	Milano
Italy	248.596.39003 Università degli studi di Napoli "Federico II"	Napoli
Italy	248.596.39001 Ospedale Civile S. Spirito, Università "G. D'Annunzio"	Pescara
Italy	248.596.39007 Clinica Neurologica Policlinico Tor Vergata	Roma
Italy	248.596.39006 Neurologia Ospedale Evangelico Valdese	Torino
Netherlands	248.596.31003 Jeroen Bosch Ziekenhuis, locatie WA	's-Hertogenbosch
Netherlands	248.596.31007 Afdeling neurologie	Amsterdam
Netherlands	248.596.31005 Ziekenhuis Gooi-Noord	Blaricum
Netherlands	248.596.31004 Amphia ziekenhuis, Locatie Molengracht	Breda
Netherlands	248.596.31002 Canisius-Wilhelmina Ziekenhuis	Nijmegen
Netherlands	248.596.31001 Maasland Ziekenhuis	Sittard
Norway	248.596.47002 Boehringer Ingelheim Investigational Site	Arendal
Norway	248.596.47004 Boehringer Ingelheim Investigational Site	Lillehammer
Norway	248.596.47003 Boehringer Ingelheim Investigational Site	Sandvika
Romania	248.596.40003 Boehringer Ingelheim Investigational Site	Bucharest
Romania	248.596.40004 Boehringer Ingelheim Investigational Site	Bucharest
Romania	248.596.40005 Boehringer Ingelheim Investigational Site	Bucharest
Romania	248.596.40001 Boehringer Ingelheim Investigational Site	Cluj Napoca
Romania	248.596.40002 Boehringer Ingelheim Investigational Site	Iasi
Romania	248.596.40006 Country Clinical Emergency Hospital	Targu-Mures
Russian Federation	248.596.70001 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	248.596.70003 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	248.596.70002 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	248.596.70004 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	248.596.70005 Boehringer Ingelheim Investigational Site	St. Petersburg
South Africa	248.596.27001 Boehringer Ingelheim Investigational Site	Cape Town
South Africa	248.596.27003 Boehringer Ingelheim Investigational Site	Cape Town
South Africa	248.596.27007 Boehringer Ingelheim Investigational Site	Cape Town
South Africa	248.596.27008 Boehringer Ingelheim Investigational Site	Johannesburg
South Africa	248.596.27004 Boehringer Ingelheim Investigational Site	Pretoria
South Africa	248.596.27006 Boehringer Ingelheim Investigational Site	Richards Bay
Spain	248.596.34003 Hospital de Alcorcón. Departamento de Neurología	Alcorcon (Madrid)
Spain	248.596.34001 Hospital Sta Creu i Sant Pau. Departamento de Neurología	Barcelona
Spain	248.596.34002 Hospital Clinic i Provincial. Departamento de Neurología	Barcelona
Spain	248.596.34005 Hosp. Univ. Vall d'Hebron. Departamento de Neurología	Barcelona
Spain	248.596.34007 Hosp Gral Univ Gregorio Marañón. Departamento de Neurología	Madrid
Spain	248.596.34004 Hospital General de Catalunya. Departamento de Neurología	San Cugat del Valles (Barcelona)
Sweden	248.596.46004 Boehringer Ingelheim Investigational Site	Linköping
Sweden	248.596.46001 Boehringer Ingelheim Investigational Site	Stockholm
Sweden	248.596.46002 Boehringer Ingelheim Investigational Site	Stockholm
Ukraine	248.596.38004 Boehringer Ingelheim Investigational Site	Donetsk
Ukraine	248.596.38005 Boehringer Ingelheim Investigational Site	Kharkiv
Ukraine	248.596.38002 Boehringer Ingelheim Investigational Site	Kiev
Ukraine	248.596.38006 Boehringer Ingelheim Investigational Site	Simferopol
Ukraine	248.596.38003 Boehringer Ingelheim Investigational Site	Vinnytzya

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Austria,  Finland,  France,  Germany,  Italy,  Netherlands,  Norway,  Romania,  Russian Federation,  South Africa,  Spain,  Sweden,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in the Beck Depression Inventory-Version 1A (BDI-IA) Total Score at Week 12	The BDI measures symptoms of depression on an ordinal scale ranging from 0 (no symptoms) to 63 (worst symptoms)	Baseline and Week 12	No
Secondary	Change in BDI-IA Clinical Response (at Least 50% Reduction in Symptoms) at Week 12	BDI clinical response was defined as a reduction of =50% from baseline	Week 12	No
Secondary	Change From Baseline in the Geriatric Depression Scale-Short Form (GDS-SF) (15-item Version) Total Score at Week 12	The GDS measures symptoms of depression on an ordinal scale ranging from 0 (no symptoms) to 15 (worst symptoms)	Baseline and Week 12	No
Secondary	Change From Baseline in Snaith-Hamilton Pleasure Scale (SHAPS) Total Score at Week 12	The SHAPS measures anhedonia (inability to experience pleasure) on an ordinal scale ranging from 0 (no anhedonia) to 14 (worst anhedonia)	Baseline and Week 12	No
Secondary	Change From Baseline in the Unified Parkinson's Disease Rating Scale (UPDRS) Part I Depression Score at Week 12	The UPDRS part I depression score measures depression on an ordinal scale ranging from 0 (none) to 4 (sustained depression/suicidal thoughts)	Baseline and Week 12	No
Secondary	Change From Baseline in the UPDRS Part II Total Score at Week 12	Unified Parkinson's Disease Rating Scale part II total score on FAS The UPDRS part II total score measures the impact of PD on activities of daily living on an ordinal scale ranging from 0 (normal) to 52 (worst symptoms)	Baseline and Week 12	No
Secondary	Change From Baseline in the UPDRS Part III Total Score at Week 12	The UPDRS part III total score measures the impact of PD on motor skills on an ordinal scale ranging from 0 (normal) to 108 (worst symptoms)	Baseline and Week 12	No
Secondary	Change From Baseline in the UPDRS Part II+III Total Score at Week 12	The UPDRS part II+III total score measures the impact of PD on activities of daily living and motor skills on an ordinal scale ranging from 0 (normal) to 160 (worst symptoms)	Baseline and Week 12	No
Secondary	Clinical Global Impressions of Global Improvement (CGI-I) at Week 12	The CGI-I measures the overall improvement in the participants condition from baseline on an ordinal scale ranging from 1 (very much improved) to 7 (very much worse)	Week 12	No
Secondary	Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Overall Index Score at Week 12	The PDQ-39 measures aspects of health in PD participants, the overall index score is the mean of the eight individual domain scores measured on a continuous scale ranging from 0 (no problem at all) to 100 (maximum level of the problem)	Baseline and Week 12	No
Secondary	Change From Baseline in the European Quality of Life Scale (EUROQOL (EQ)-5D) Overall Index Score at Week 12	This is a 5-item patient reported measure of health status developed for use in evaluating health and healthcare. It produces a numeric score for health status on which full health has a value of 1 and death has a value of 0. Euro-QOL describes health status in terms of 5 dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. The EQ-5D measures health status on a continuous scale ranging from 0 (dead) to 1 (full health)	Baseline and Week 12	No
Secondary	Change From Baseline to End of Maintenance Phase in European Quality of Life Visual Analogue Scale (EUROQOL (EQ) VAS) Pain Score at Week 12	The VAS is a method used for the measurement of pain. The patient is asked to place a mark on an uncalibrated (usually 0 - 10 cm) line representing the patient's degree of general pain. The two extremities of the line were taken to represent 'no pain' and 'unbearable pain', respectively. VAS pain scores could range from 0 (no pain) to 100 (unbearable pain).	Baseline and Week 12	No
Secondary	Change From Baseline in the UPDRS Part I Total Score at Week 12	The UPDRS part I total score measures depression on an ordinal scale ranging from 0 to 16. UPDRS Part I total scores could range from 0 to 16; where higher scores were indicative of worse symptoms.	Baseline and Week 12	No
Secondary	Change From Baseline in the UPDRS Part IV Total Score at Week 12	The UPDRS Part IV measures motor complications (dyskinesia) and the total score could range from 0 to 23; where higher scores were indicative of worse symptoms.	Baseline and Week 12	No
Secondary	Abnormal Findings: Clinical Laboratory Evaluations (Biochemistry and Haematology)and Vital Signs		Baseline and Week 12	Yes

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