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

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00297778
• Collaborator: (none)
• Enrollment: 296
• Locations: 77
• Arms: 2
• Patients Per Site: 3.8

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease; Depression	Drug: Pramipexole; Other: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 296 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: May 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: pramipexole A daily dose of pramipexole 0.125 mg t.i.d.; titration-to-response up to 1.0 mg t.i.d.	Drug: Pramipexole; Dopamine agonist
Placebo Comparator: placebo Placebo (matching) tablets	Other: Placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the Beck Depression Inventory-Version 1A (BDI-IA) Total Score at Week 12 [Baseline and Week 12]

   The BDI measures symptoms of depression on an ordinal scale ranging from 0 (no symptoms) to 63 (worst symptoms)

Secondary Outcome Measures

1. Change in BDI-IA Clinical Response (at Least 50% Reduction in Symptoms) at Week 12 [Week 12]

   BDI clinical response was defined as a reduction of ≥50% from baseline

2. Change From Baseline in the Geriatric Depression Scale-Short Form (GDS-SF) (15-item Version) Total Score at Week 12 [Baseline and Week 12]

   The GDS measures symptoms of depression on an ordinal scale ranging from 0 (no symptoms) to 15 (worst symptoms)

3. Change From Baseline in Snaith-Hamilton Pleasure Scale (SHAPS) Total Score at Week 12 [Baseline and Week 12]

   The SHAPS measures anhedonia (inability to experience pleasure) on an ordinal scale ranging from 0 (no anhedonia) to 14 (worst anhedonia)

4. Change From Baseline in the Unified Parkinson's Disease Rating Scale (UPDRS) Part I Depression Score at Week 12 [Baseline and Week 12]

   The UPDRS part I depression score measures depression on an ordinal scale ranging from 0 (none) to 4 (sustained depression/suicidal thoughts)

5. Change From Baseline in the UPDRS Part II Total Score at Week 12 [Baseline and 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)

6. Change From Baseline in the UPDRS Part III Total Score at Week 12 [Baseline and 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)

7. Change From Baseline in the UPDRS Part II+III Total Score at Week 12 [Baseline and 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)

8. Clinical Global Impressions of Global Improvement (CGI-I) at Week 12 [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)

9. Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Overall Index Score at Week 12 [Baseline and 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)

10. Change From Baseline in the European Quality of Life Scale (EUROQOL (EQ)-5D) Overall Index Score at Week 12 [Baseline and 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)

11. Change From Baseline to End of Maintenance Phase in European Quality of Life Visual Analogue Scale (EUROQOL (EQ) VAS) Pain Score at Week 12 [Baseline and 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).

12. Change From Baseline in the UPDRS Part I Total Score at Week 12 [Baseline and 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.

13. Change From Baseline in the UPDRS Part IV Total Score at Week 12 [Baseline and 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.

14. Abnormal Findings: Clinical Laboratory Evaluations (Biochemistry and Haematology)and Vital Signs [Baseline and Week 12]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	248.596.43003 Boehringer Ingelheim Investigational Site	Graz		Austria
2	248.596.43001 Boehringer Ingelheim Investigational Site	Innsbruck		Austria
3	248.596.43005 Boehringer Ingelheim Investigational Site	Linz		Austria
4	248.596.43004 Boehringer Ingelheim Investigational Site	St. Pölten		Austria
5	248.596.43002 Boehringer Ingelheim Investigational Site	Wien		Austria
6	248.596.35801 Boehringer Ingelheim Investigational Site	Oulu		Finland
7	248.596.3302B Centre Hospitalier du Pays d'Aix	Aix en Provence cedex 1		France
8	248.596.3302A Centre Hospitalier du Pays d'Aix	Aix en Provence		France
9	248.596.3306A Hôpital Pierre Wertheimer	Bron cedex		France
10	248.596.3308A Hôpital Gabriel Montpied	Clermont Ferrand		France
11	248.596.3309A Cabinet Médical	Evreux		France
12	248.596.3307A Hôpital Roger Salengro	Lille cedex		France
13	248.596.3307B Hôpital Roger Salengro	Lille cedex		France
14	248.596.3307C Hôpital Roger Salengro	Lille cedex		France
15	248.596.3303A Hôpital La Timone	Marseille cedex 5		France
16	248.596.3305A Hôpital du Haut Levêque	Pessac cédex		France
17	248.596.3305B Hôpital du Haut Levêque	Pessac cédex		France
18	248.596.3301A Hôpital Guillaume et René Laennec	Saint Herblain		France
19	248.596.49012 Boehringer Ingelheim Investigational Site	Berlin-Steglitz		Germany
20	248.596.49002 Boehringer Ingelheim Investigational Site	Berlin		Germany
21	248.596.49013 Boehringer Ingelheim Investigational Site	Berlin		Germany
22	248.596.49015 Boehringer Ingelheim Investigational Site	Berlin		Germany
23	248.596.49003 Boehringer Ingelheim Investigational Site	Bremerhaven		Germany
24	248.596.49004 Boehringer Ingelheim Investigational Site	Gera		Germany
25	248.596.49001 Boehringer Ingelheim Investigational Site	Karlsruhe		Germany
26	248.596.49016 Boehringer Ingelheim Investigational Site	Köln		Germany
27	248.596.49005 Boehringer Ingelheim Investigational Site	Marburg		Germany
28	248.596.49014 Boehringer Ingelheim Investigational Site	Mittweida		Germany
29	248.596.49008 Boehringer Ingelheim Investigational Site	München		Germany
30	248.596.39008 Clinica Neurologica I Policlinico di Catania	Catania		Italy
31	248.596.39004 Neurologia Ospedale della Misericordia	Grosseto		Italy
32	248.596.39005 Clinica Neurologica Policlinico G. Martino	Messina		Italy
33	248.596.39009 Istituti Clinici di Perfezionamento	Milano		Italy
34	248.596.39003 Università degli studi di Napoli "Federico II"	Napoli		Italy
35	248.596.39001 Ospedale Civile S. Spirito, Università "G. D'Annunzio"	Pescara		Italy
36	248.596.39007 Clinica Neurologica Policlinico Tor Vergata	Roma		Italy
37	248.596.39006 Neurologia Ospedale Evangelico Valdese	Torino		Italy
38	248.596.31003 Jeroen Bosch Ziekenhuis, locatie WA	's-Hertogenbosch		Netherlands
39	248.596.31007 Afdeling neurologie	Amsterdam		Netherlands
40	248.596.31005 Ziekenhuis Gooi-Noord	Blaricum		Netherlands
41	248.596.31004 Amphia ziekenhuis, Locatie Molengracht	Breda		Netherlands
42	248.596.31002 Canisius-Wilhelmina Ziekenhuis	Nijmegen		Netherlands
43	248.596.31001 Maasland Ziekenhuis	Sittard		Netherlands
44	248.596.47002 Boehringer Ingelheim Investigational Site	Arendal		Norway
45	248.596.47004 Boehringer Ingelheim Investigational Site	Lillehammer		Norway
46	248.596.47003 Boehringer Ingelheim Investigational Site	Sandvika		Norway
47	248.596.40003 Boehringer Ingelheim Investigational Site	Bucharest		Romania
48	248.596.40004 Boehringer Ingelheim Investigational Site	Bucharest		Romania
49	248.596.40005 Boehringer Ingelheim Investigational Site	Bucharest		Romania
50	248.596.40001 Boehringer Ingelheim Investigational Site	Cluj Napoca		Romania
51	248.596.40002 Boehringer Ingelheim Investigational Site	Iasi		Romania
52	248.596.40006 Country Clinical Emergency Hospital	Targu-Mures		Romania
53	248.596.70001 Boehringer Ingelheim Investigational Site	Moscow		Russian Federation
54	248.596.70003 Boehringer Ingelheim Investigational Site	Moscow		Russian Federation
55	248.596.70002 Boehringer Ingelheim Investigational Site	St. Petersburg		Russian Federation
56	248.596.70004 Boehringer Ingelheim Investigational Site	St. Petersburg		Russian Federation
57	248.596.70005 Boehringer Ingelheim Investigational Site	St. Petersburg		Russian Federation
58	248.596.27001 Boehringer Ingelheim Investigational Site	Cape Town		South Africa
59	248.596.27003 Boehringer Ingelheim Investigational Site	Cape Town		South Africa
60	248.596.27007 Boehringer Ingelheim Investigational Site	Cape Town		South Africa
61	248.596.27008 Boehringer Ingelheim Investigational Site	Johannesburg		South Africa
62	248.596.27004 Boehringer Ingelheim Investigational Site	Pretoria		South Africa
63	248.596.27006 Boehringer Ingelheim Investigational Site	Richards Bay		South Africa
64	248.596.34003 Hospital de Alcorcón. Departamento de Neurología	Alcorcon (Madrid)		Spain
65	248.596.34001 Hospital Sta Creu i Sant Pau. Departamento de Neurología	Barcelona		Spain
66	248.596.34002 Hospital Clinic i Provincial. Departamento de Neurología	Barcelona		Spain
67	248.596.34005 Hosp. Univ. Vall d'Hebron. Departamento de Neurología	Barcelona		Spain
68	248.596.34007 Hosp Gral Univ Gregorio Marañón. Departamento de Neurología	Madrid		Spain
69	248.596.34004 Hospital General de Catalunya. Departamento de Neurología	San Cugat del Valles (Barcelona)		Spain
70	248.596.46004 Boehringer Ingelheim Investigational Site	Linköping		Sweden
71	248.596.46001 Boehringer Ingelheim Investigational Site	Stockholm		Sweden
72	248.596.46002 Boehringer Ingelheim Investigational Site	Stockholm		Sweden
73	248.596.38004 Boehringer Ingelheim Investigational Site	Donetsk		Ukraine
74	248.596.38005 Boehringer Ingelheim Investigational Site	Kharkiv		Ukraine
75	248.596.38002 Boehringer Ingelheim Investigational Site	Kiev		Ukraine
76	248.596.38006 Boehringer Ingelheim Investigational Site	Simferopol		Ukraine
77	248.596.38003 Boehringer Ingelheim Investigational Site	Vinnytzya		Ukraine

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT00297778
• Other Study ID Numbers: 248.596; Eudract 2005-003788-22
• First Posted: Mar 1, 2006
• Last Update Posted: Jun 9, 2014
• Last Verified: Apr 1, 2014

• Additional relevant MeSH terms: Parkinson Disease; Depression; Pramipexole

Study Results

Participant Flow

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablet matching active treatment	Ascending dose titration of Pramipexole. Pramipexole doses consisted of 0.125 mg three times daily (t.i.d), 0.25mg t.i.d, 0.5mg, t.i.d, 0.25mg+0.5mg t.i.d and 1.0 mg t.i.d.
Period Title: Overall Study
STARTED	152	144
COMPLETED	133	124
NOT COMPLETED	19	20

Baseline Characteristics

Arm/Group Title	Placebo	Pramipexole	Total
Arm/Group Description	Placebo tablet matching active treatment	Ascending dose titration of Pramipexole. Pramipexole doses consisted of 0.125 mg three times daily (t.i.d), 0.25mg t.i.d, 0.5mg, t.i.d, 0.25mg+0.5mg t.i.d and 1.0 mg t.i.d.	Total of all reporting groups
Overall Participants	152	144	296
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	66.6 (9.9)	67.4 (9.0)	67 (9.5)
Sex: Female, Male (Count of Participants)
Female	74 48.7%	82 56.9%	156 52.7%
Male	78 51.3%	62 43.1%	140 47.3%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Beck Depression Inventory-Version 1A (BDI-IA) Total Score at Week 12
Description	The BDI measures symptoms of depression on an ordinal scale ranging from 0 (no symptoms) to 63 (worst symptoms)
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

The Full analysis set (FAS) made up of all randomised and treated participants with a baseline and at least one on-treatment assessment of the BDI. 9 participants from those randomised and treated were excluded due to insufficient BDI data.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablet matching active treatment	Ascending dose titration of Pramipexole. Pramipexole doses consisted of 0.125 mg three times daily (t.i.d), 0.25mg t.i.d, 0.5mg, t.i.d, 0.25mg+0.5mg t.i.d and 1.0 mg t.i.d.
Measure Participants	148	139
Least Squares Mean (Standard Error) [Score on scale]	-4 (0.5)	-5.9 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0103
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.9
	Confidence Interval	() 95%; -3.4 to -0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in BDI-IA Clinical Response (at Least 50% Reduction in Symptoms) at Week 12
Description	BDI clinical response was defined as a reduction of ≥50% from baseline
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

FAS. 10 participants from those randomised and treated were excluded due to insufficient BDI data (1 due to a zero baseline score).

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablet matching active treatment	Ascending dose titration of Pramipexole. Pramipexole doses consisted of 0.125 mg three times daily (t.i.d), 0.25mg t.i.d, 0.5mg, t.i.d, 0.25mg+0.5mg t.i.d and 1.0 mg t.i.d.
Measure Participants	147	139
Number [participants]	27 17.8%	38 26.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0535
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.758
	Confidence Interval	() 95%; 0.992 to 3.115
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in the Geriatric Depression Scale-Short Form (GDS-SF) (15-item Version) Total Score at Week 12
Description	The GDS measures symptoms of depression on an ordinal scale ranging from 0 (no symptoms) to 15 (worst symptoms)
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS. 9 participants from those randomised and treated were excluded due to insufficient GDS data.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablet matching active treatment	Ascending dose titration of Pramipexole. Pramipexole doses consisted of 0.125 mg three times daily (t.i.d), 0.25mg t.i.d, 0.5mg, t.i.d, 0.25mg+0.5mg t.i.d and 1.0 mg t.i.d.
Measure Participants	148	139
Least Squares Mean (Standard Error) [units on a scale]	-1.7 (0.3)	-2.5 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0346
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.8
	Confidence Interval	() 95%; -1.5 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Snaith-Hamilton Pleasure Scale (SHAPS) Total Score at Week 12
Description	The SHAPS measures anhedonia (inability to experience pleasure) on an ordinal scale ranging from 0 (no anhedonia) to 14 (worst anhedonia)
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS. 9 participants from those randomised and treated were excluded due to insufficient SHAPS data.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablet matching active treatment	Ascending dose titration of Pramipexole. Pramipexole doses consisted of 0.125 mg three times daily (t.i.d), 0.25mg t.i.d, 0.5mg, t.i.d, 0.25mg+0.5mg t.i.d and 1.0 mg t.i.d.
Measure Participants	148	139
Median (Inter-Quartile Range) [units on a scale]	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5244
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0
	Confidence Interval	() 95%; -1 to 0
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in the Unified Parkinson's Disease Rating Scale (UPDRS) Part I Depression Score at Week 12
Description	The UPDRS part I depression score measures depression on an ordinal scale ranging from 0 (none) to 4 (sustained depression/suicidal thoughts)
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS. 9 participants from those randomised and treated were excluded due to insufficient UPDRS data.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablet matching active treatment	Ascending dose titration of Pramipexole. Pramipexole doses consisted of 0.125 mg three times daily (t.i.d), 0.25mg t.i.d, 0.5mg, t.i.d, 0.25mg+0.5mg t.i.d and 1.0 mg t.i.d.
Measure Participants	148	139
Median (Inter-Quartile Range) [units on a scale]	-1	-1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.141
	Comments
	Method	van Elteren (country stratification)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	0
	Confidence Interval	() 95%; 0 to 0
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in the UPDRS Part II Total Score at Week 12
Description	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)
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS. 9 participants from those randomised and treated were excluded due to insufficient UPDRS data.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablet matching active treatment	Ascending dose titration of Pramipexole. Pramipexole doses consisted of 0.125 mg three times daily (t.i.d), 0.25mg t.i.d, 0.5mg, t.i.d, 0.25mg+0.5mg t.i.d and 1.0 mg t.i.d.
Measure Participants	148	139
Least Squares Mean (Standard Error) [units on a scale]	-1.2 (0.3)	-2.4 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.2
	Confidence Interval	() 95%; -1.9 to -0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in the UPDRS Part III Total Score at Week 12
Description	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)
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS. 10 participants from those randomised and treated were excluded due to insufficient UPDRS data.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablet matching active treatment	Ascending dose titration of Pramipexole. Pramipexole doses consisted of 0.125 mg three times daily (t.i.d), 0.25mg t.i.d, 0.5mg, t.i.d, 0.25mg+0.5mg t.i.d and 1.0 mg t.i.d.
Measure Participants	148	138
Least Squares Mean (Standard Error) [units on a scale]	-2.2 (0.5)	-4.4 (0.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0034
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.2
	Confidence Interval	() 95%; -3.7 to -0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in the UPDRS Part II+III Total Score at Week 12
Description	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)
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS. 10 participants from those randomised and treated were excluded due to insufficient UPDRS data.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablet matching active treatment	Ascending dose titration of Pramipexole. Pramipexole doses consisted of 0.125 mg three times daily (t.i.d), 0.25mg t.i.d, 0.5mg, t.i.d, 0.25mg+0.5mg t.i.d and 1.0 mg t.i.d.
Measure Participants	148	138
Least Squares Mean (Standard Error) [units on a scale]	-3.4 (0.7)	-6.8 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.4
	Confidence Interval	() 95%; -5.4 to -1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Clinical Global Impressions of Global Improvement (CGI-I) at Week 12
Description	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)
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

FAS. 9 participants from those randomised and treated were excluded due to insufficient CGI-I data.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablet matching active treatment	Ascending dose titration of Pramipexole. Pramipexole doses consisted of 0.125 mg three times daily (t.i.d), 0.25mg t.i.d, 0.5mg, t.i.d, 0.25mg+0.5mg t.i.d and 1.0 mg t.i.d.
Measure Participants	148	139
Median (Full Range) [units on a scale]	3	3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.821
	Confidence Interval	() 95%; 1.187 to 2.794
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) Overall Index Score at Week 12
Description	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)
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS. 52 participants from those randomised and treated were excluded due to insufficient PDQ-39 data.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablet matching active treatment	Ascending dose titration of Pramipexole. Pramipexole doses consisted of 0.125 mg three times daily (t.i.d), 0.25mg t.i.d, 0.5mg, t.i.d, 0.25mg+0.5mg t.i.d and 1.0 mg t.i.d.
Measure Participants	127	108
Median (Inter-Quartile Range) [units on a scale]	-2.4	-3.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1925
	Comments
	Method	van Elteren (country stratification)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-1.3
	Confidence Interval	() 95%; -3.3 to 0.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline in the European Quality of Life Scale (EUROQOL (EQ)-5D) Overall Index Score at Week 12
Description	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)
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS. 16 participants from those randomised and treated were excluded due to insufficient EQ-5D data.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablet matching active treatment	Ascending dose titration of Pramipexole. Pramipexole doses consisted of 0.125 mg three times daily (t.i.d), 0.25mg t.i.d, 0.5mg, t.i.d, 0.25mg+0.5mg t.i.d and 1.0 mg t.i.d.
Measure Participants	144	136
Median (Inter-Quartile Range) [units on a scale]	0	0.07

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0337
	Comments
	Method	Wilcoxon rank sum (Van Elteren's test)
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehmann est of diff in medians
	Estimated Value	0.04
	Confidence Interval	() 95%; 0 to 0.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Change From Baseline to End of Maintenance Phase in European Quality of Life Visual Analogue Scale (EUROQOL (EQ) VAS) Pain Score at Week 12
Description	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).
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS. 15 participants from those randomised and treated were excluded due to insufficient EQ-5D data.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablet matching active treatment	Ascending dose titration of Pramipexole. Pramipexole doses consisted of 0.125 mg three times daily (t.i.d), 0.25mg t.i.d, 0.5mg, t.i.d, 0.25mg+0.5mg t.i.d and 1.0 mg t.i.d.
Measure Participants	148	139
Least Squares Mean (Standard Error) [mm]	-3 (1.8)	-3.5 (1.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8471
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.5
	Confidence Interval	() 95%; -5.6 to 4.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Change From Baseline in the UPDRS Part I Total Score at Week 12
Description	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.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS. 9 participants from those randomised and treated were excluded due to insufficient UPDRS data.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablet matching active treatment	Ascending dose titration of Pramipexole. Pramipexole doses consisted of 0.125 mg three times daily (t.i.d), 0.25mg t.i.d, 0.5mg, t.i.d, 0.25mg+0.5mg t.i.d and 1.0 mg t.i.d.
Measure Participants	148	139
Median (Inter-Quartile Range) [units on a scale]	-1.0	-1.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments	N's exclude patients from the analysis set with incomplete data
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1410
	Comments
	Method	Wilcoxon rank sum (Van Elteren's test)
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehmann est of diff in medians
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; 0.0 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% Confidence interval is Distribution-free Confidence Interval (Moses).

14. Secondary Outcome

Title	Change From Baseline in the UPDRS Part IV Total Score at Week 12
Description	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.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

FAS. 28 participants from those randomised and treated were excluded due to insufficient UPDRS data.

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablet matching active treatment	Ascending dose titration of Pramipexole. Pramipexole doses consisted of 0.125 mg three times daily (t.i.d), 0.25mg t.i.d, 0.5mg, t.i.d, 0.25mg+0.5mg t.i.d and 1.0 mg t.i.d.
Measure Participants	137	131
Least Squares Mean (Standard Error) [units on a scale]	-0.2 (0.1)	-0.3 (0.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Pramipexole
	Comments	N's exclude patients from the analysis set with incomplete data
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5231
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.5 to 0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2
	Estimation Comments

15. Secondary Outcome

Title	Abnormal Findings: Clinical Laboratory Evaluations (Biochemistry and Haematology)and Vital Signs
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Pramipexole
Arm/Group Description	Placebo tablet matching active treatment	Ascending dose titration of Pramipexole. Pramipexole doses consisted of 0.125 mg three times daily (t.i.d), 0.25mg t.i.d, 0.5mg, t.i.d, 0.25mg+0.5mg t.i.d and 1.0 mg t.i.d.
Measure Participants	152	144
Hypotension	1 0.7%	1 0.7%
Orthostatic hypotension	1 0.7%	0 0%

Adverse Events

Time Frame	First drug intake up to 48 hours after the last drug intake
Arm/Group Title	Placebo		Pramipexole
Arm/Group Description	Placebo tablet matching active treatment		Ascending dose titration of Pramipexole. Pramipexole doses consisted of 0.125 mg three times daily (t.i.d), 0.25mg t.i.d, 0.5mg, t.i.d, 0.25mg+0.5mg t.i.d and 1.0 mg t.i.d.
All Cause Mortality
	Placebo		Pramipexole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Pramipexole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/ (NaN)		6/ (NaN)
Cardiac disorders
Angina unstable	1/152 (0.7%)		0/144 (0%)
Cardiac failure	1/152 (0.7%)		1/144 (0.7%)
Gastrointestinal disorders
Abdominal pain	1/152 (0.7%)		0/144 (0%)
Gastroduodenal ulcer	1/152 (0.7%)		0/144 (0%)
Volvulus	1/152 (0.7%)		0/144 (0%)
Infections and infestations
Endocarditis	0/152 (0%)		1/144 (0.7%)
Injury, poisoning and procedural complications
Accident at home	1/152 (0.7%)		0/144 (0%)
Comminuted fracture	1/152 (0.7%)		0/144 (0%)
Fall	1/152 (0.7%)		1/144 (0.7%)
Femoral neck fracture	0/152 (0%)		1/144 (0.7%)
Skull fracture base	1/152 (0.7%)		0/144 (0%)
Traumatic brain injury	1/152 (0.7%)		0/144 (0%)
Metabolism and nutrition disorders
Hyperlipidaemia	0/152 (0%)		1/144 (0.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/152 (0%)		1/144 (0.7%)
Spinal osteoarthritis	1/152 (0.7%)		0/144 (0%)
Nervous system disorders
Cerebral haemorrhage	0/152 (0%)		1/144 (0.7%)
Cerebrovascular accident	0/152 (0%)		1/144 (0.7%)
Parkinson disease	1/152 (0.7%)		0/144 (0%)
Radicular pain	1/152 (0.7%)		0/144 (0%)
Syncope	0/152 (0%)		1/144 (0.7%)
Psychiatric disorders
Hallucination	0/152 (0%)		1/144 (0.7%)
Renal and urinary disorders
Anuria	0/152 (0%)		1/144 (0.7%)
Other (Not Including Serious) Adverse Events
	Placebo		Pramipexole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	58/ (NaN)		71/ (NaN)
Ear and labyrinth disorders
Vertigo	4/152 (2.6%)		10/144 (6.9%)
Gastrointestinal disorders
Nausea	26/152 (17.1%)		24/144 (16.7%)
General disorders
Fatigue	9/152 (5.9%)		8/144 (5.6%)
Nervous system disorders
Dizziness	9/152 (5.9%)		16/144 (11.1%)
Headache	12/152 (7.9%)		16/144 (11.1%)
Somnolence	12/152 (7.9%)		15/144 (10.4%)
Dyskinesia	4/152 (2.6%)		10/144 (6.9%)
Psychiatric disorders
Insomnia	4/152 (2.6%)		8/144 (5.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.