Pramipexole in Out-patients With Idiopathic Restless Legs Syndrome (IRLS)

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00654498
• Collaborator: (none)
• Enrollment: 306
• Locations: 16
• Arms: 2
• Duration (Months): 14
• Patients Per Site: 19.1
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

To determine efficacy and safety of Pramipexole 0.125mg to 0.75mg daily for 6 weeks compared to placebo in the treatment of idiopathic Restless Legs Syndrome (RLS)

Condition or Disease	Intervention/Treatment	Phase
Restless Legs Syndrome	Drug: Pramipexole; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 306 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 Dose Titration Trial With 0.125-0.75 mg Pramipexole (Sifrol®) Orally q.n. to Investigate the Safety and Efficacy in Out-patients With Idiopathic Restless Legs Syndrome for 6 Weeks
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Other: Pramipexole 4 weeks of individual dose titration starting with Pramipexole 0.125 mg, next dose steps 0.25 mg, 0.5 mg and 0.75 mg, fixed dose for 2 weeks, once daily	Drug: Pramipexole
Other: Placebo 4 weeks of individual dose titration as for the investigational product, once daily	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. The Change From Baseline to Week 6 in the Total Score of Restless Legs Syndrome Rating Scale for Severity of the International Restless Legs Syndrome Study Group (IRLS). [Baseline and 6 weeks of treatment]

   The IRLS was a 10-item self patient's rating scale for assessing severity of restless legs syndrome symptoms with each item ranging from 0 (no symptoms) to 4 (very severe symptoms). The total IRLS score ranges from 0 (no symptoms) to 40 (worst possible symptoms).

2. The Proportion of Patients With Clinical Global Impressions -Improvement Scale (CGI-I) Assessment of "Much Improved" and "Very Much Improved" [6 weeks of treatment]

   CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved)and 2 (much improved.

Secondary Outcome Measures

1. The Proportion of IRLS Responders [6 weeks of treatment]

   responders is defined as the total score in IRLS changed ≥ 50%from baseline calculated in the full analysis set population.

2. The Proportion of Patient Global Impression(PGI) Responders [6 weeks of treatment]

   PGI was a one-question scale with 7 degrees to assess patient's overall condition, ranging from very much better to very much worse. The responder are defined as patients with their assessment of "much better" or "very much better".

3. The Proportion of Patients With Epworth Sleepiness Scale (ESS) Categorised >10 [week 6 of treatment]

   The ESS is a self-administered instrument to assess the patients likelihood of falling asleep in various activities of daily living; the maximum score is 24 indicating a very high level of daytime sleepiness and a high likelihood of falling asleep.

4. the Mean Change From Baseline to Week 6 in Satisfaction of Sleep at Night of RLS-6 Rating Scales [Baseline and 6 weeks of treatment]

   RLS-6 rating scales comprises 6 questions Satisfaction of sleep is one of the 6 questions. The patient should give a rate between 0 (none/Not at all) to 10 (very severe) for the satisfaction of sleep.

5. The Mean Change From Baseline in the Severity of RLS at Time of Falling Sleep of RLS-6 Rating Scales. [Baseline and 6 weeks of treatment]

   RLS-6 rating scales comprises 6 questions. The severity of RLS at time of falling sleep is one of the 6 questions. The patient should give a rate between 0 (none/Not at all) to 10 (very severe) for the severity of RLS at time of falling sleep

6. The Mean Change From Baseline in the Severity of RLS During the Night of RLS-6 Rating Scales. [Baseline and 6 weeks of treatment]

   RLS-6 rating scales comprises 6 questions. The severity of RLS during the night is one of the 6 questions. The patient should give a rate between 0 ("none/Not at all") to 10 ("very severe") for the severity of RLS during the night.

7. The Mean Change From Baseline in the Severity of RLS During the Rest at Day of RLS-6 Rating Scales. [Baseline and 6 weeks of treatment]

   RLS-6 rating scales comprises 6 questions. The severity of RLS during the test at day is one of the 6 questions. The patient should give a rate between 0 ("none/Not at all") to 10 ("very severe") for the severity of RLS during the rest at day.

8. The Mean Change From Baseline in the Severity of RLS During the Activities at Day of RLS-6 Rating Scale [Baseline and 6 weeks of treatment]

   RLS-6 rating scales comprises 6 questions. The severity of RLS during the activities at day is one of the 6 questions. The patient should give a rate between 0 ("none/Not at all") to 10 ("very severe") for the severity of RLS during the activity at day.

9. The Mean Change From Baseline in the Intensity of Tiredness and Sleepiness at Day of RLS-6 Rating Scale [Baseline and 6 weeks of treatment]

   RLS-6 rating scales comprises 6 questions. The intensity of tiredness and sleepiness at day is one of the 6 questions. The patient should give a rate between 0 ("none/Not at all") to 10 ("very severe") for the intensity of tiredness and sleepiness at day.

10. The Change From Baseline in Visual Analogue Scales (VAS) [Baseline and 6 weeks of treatment]

    VAS is for assessment of RLS-associated pain. The patient was asked "How severe was your RLS associated pain in legs or arms during the past week?". No pain:0; very worst pain:10

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Written informed consent consistent with International Conference on Harmonisation (ICH) / Good Clinical Practice (GCP) and local legislation given prior to any study procedures.

2. Ability and willingness to comply with study treatment regimen and to attend study assessments.

3. Male or female out-patients aged 18-80 years.

4. Diagnosis of idiopathic Restless Legs Syndrome (IRLS) according to the clinical Restless Legs Syndrome (RLS) criteria of the International Restless Legs Syndrome Study Group (IRLSSG)

All four criteria must be present to fulfil the diagnosis of RLS:

• An urge to move the legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs. (Sometimes the urge to move is present without the uncomfortable sensations and sometimes the arms or other body parts are involved in addition to the legs).

• The urge to move or unpleasant sensations begin or worsen during periods of rest or inactivity such as lying or sitting.

• The urge to move or unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues.

• The urge to move or unpleasant sensations are worse in the evening or night than during the day or only occur in the evening or night. (When symptoms are very severe, the worsening at night may not be noticeable but must have been previously present).

1. Restless Legs Syndrome (RLS)rating scale for severity total score >15.

2. Restless Legs Syndrome (RLS) symptoms present at least 2 to 3 days per week during the last 3 months.

Exclusion Criteria:

1. Women of child-bearing potential (i.e. premenopausal women, or postmenopausal women less than 2 years after last menses) who do not use during the clinical trial an adequate method of contraception such as: hormonal therapy (combined oral contraceptives, injectables, or subcutaneous implants), hormonal intrauterine devices, sexual abstinence, surgical sterilization of patient and/or partner, hysterectomy, bilateral ovariectomy or partners vasectomy

2. Any woman of child-bearing potential not having a negative pregnancy test at screening

3. Patients who are breastfeeding

4. Concomitant or previous pharmacologically therapy of RLS as follows:

• Any intake of levodopa within 5 days prior to baseline visit (V2)

• Any intake of dopamine agonists within 14 days prior to baseline visit (V2)

1. Current (less than 14 days before treatment with trial medication or concomitant) treatment with medication or dietary supplements, which could significantly influence RLS symptoms, e.g. dopaminergic (other than levodopa or dopamine agonists) or anti-dopaminergic drugs, non-selective Monoamine Oxidase (MAO) inhibitors, sympathomimetics, neuroleptics, anti-depressants, hypnotics, any benzodiazepines, antiepileptics, opioids, clonidine, magnesium, ferrous salts, Folic acid, vitamin B12, antihistaminics, lithium, metoclopramide or Withdrawal symptoms caused by stopping any of the drugs above

2. Confirmed diagnose of diabetic nephropathy or clinically significant renal disease

3. Creatinine higher than upper limit of normal (ULN) at screening

4. Clinical significant hepatic disease or Alanine aminotransferase (ALT) >2 times the upper limit of normal range at screening

5. Clinical or laboratory signs of microcytic anaemia, or ferritin in serum below the lower bound of the reference range

6. Any of the following lab results at screening:

• Basal Thyroid Stimulating Hormone (TSH), T3 or T4 clinically significantly (at the investigators discretion) out of normal range at screening (if not caused by substitution therapy according the investigators opinion)

• Patients with any clinically significant abnormalities in laboratory parameters at screening at the investigators discretion

1. Other clinically significant metabolic-endocrine, haematological, gastro-intestinal disease or pulmonary disease (such as severe COPD). Poorly controlled cardiovascular disease (including hypotension and severe coronary artery disease)

2. History or clinical signs of peripheral neuropathy (PNP) of any origin in physical, neuro-logical examination, myelopathy or multiple sclerosis or any other neurological disease, with potential to secondarily cause RLS symptoms

3. Presence of any other sleep disorder, such as, Rapid Eye Movement (REM) sleep behaviour disorder, narcolepsy or sleep apnoea syndrome

4. History of Schizophrenia or any psychotic disorder, history of mental disorders due to a general medical condition or any present axis I psychiatric disorder according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM IV) requiring any medical therapy

5. History of alcohol abuse or drug addiction within the last 2 years before screening

6. Participation in a drug study within two months prior to the start of this study

7. History of or clinical signs for any form of epilepsy or seizures apart from fever related seizures in early childhood

8. History of or clinical signs of malign neoplasm

9. Patients on a shift-work-schedule, or who are otherwise unable to follow a regular sleep-wake cycle enabling use of study medication at times indicated

10. Any other conditions that in the opinion of the investigator would interfere with the evaluation of the results or constitute a health hazard for the subject

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	248.630.04 Boehringer Ingelheim Investigational Site	Beijing		China
2	248.630.05 Boehringer Ingelheim Investigational Site	Beijing		China
3	248.630.06 Boehringer Ingelheim Investigational Site	Beijing		China
4	248.630.07 Boehringer Ingelheim Investigational Site	Beijing		China
5	248.630.08 Boehringer Ingelheim Investigational Site	Beijing		China
6	248.630.15 Boehringer Ingelheim Investigational Site	Guangzhou		China
7	248.630.14 Boehringer Ingelheim Investigational Site	Haerbin		China
8	248.630.10 Boehringer Ingelheim Investigational Site	Hangzhou		China
9	248.630.09 Boehringer Ingelheim Investigational Site	Nanjing		China
10	248.630.12 Boehringer Ingelheim Investigational Site	Qingdao		China
11	248.630.01 Boehringer Ingelheim Investigational Site	Shanghai		China
12	248.630.02 Boehringer Ingelheim Investigational Site	Shanghai		China
13	248.630.03 Boehringer Ingelheim Investigational Site	Shanghai		China
14	248.630.16 Boehringer Ingelheim Investigational Site	Suzhou		China
15	248.630.13 Boehringer Ingelheim Investigational Site	Wuhan		China
16	248.630.11 Boehringer Ingelheim Investigational Site	Xian, Shanxi Province		China

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT00654498
• Other Study ID Numbers: 248.630
• First Posted: Apr 8, 2008
• Last Update Posted: Jun 9, 2014
• Last Verified: Mar 1, 2014

• Additional relevant MeSH terms: Psychomotor Agitation; Restless Legs Syndrome; Syndrome; Pramipexole

Study Results

Participant Flow

Arm/Group Title	Pramipexole	Placebo
Arm/Group Description	4 weeks of individual dose titration starting with 0.125 mg pramipexole, next dose steps 0.25 mg, 0.5 mg and 0.75 mg, fixed dose for 2 weeks, once daily	1 tablet (Pramipexole 0.125 mg matching placebo tablet), or 1 or 2 or 3 tablets (Pramipexole 0.25 mg matching placebo tablet), once daily
Period Title: Overall Study
STARTED	203	103
COMPLETED	189	91
NOT COMPLETED	14	12

Baseline Characteristics

Arm/Group Title	Pramipexole	Placebo	Total
Arm/Group Description	Total of all reporting groups
Overall Participants	202	103	305
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.46 (11.88)	56.86 (11.89)	56.6 (11.87)
Sex: Female, Male (Count of Participants)
Female	122 60.4%	75 72.8%	197 64.6%
Male	80 39.6%	28 27.2%	108 35.4%

Outcome Measures

1. Primary Outcome

Title	The Change From Baseline to Week 6 in the Total Score of Restless Legs Syndrome Rating Scale for Severity of the International Restless Legs Syndrome Study Group (IRLS).
Description	The IRLS was a 10-item self patient's rating scale for assessing severity of restless legs syndrome symptoms with each item ranging from 0 (no symptoms) to 4 (very severe symptoms). The total IRLS score ranges from 0 (no symptoms) to 40 (worst possible symptoms).
Time Frame	Baseline and 6 weeks of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS), All patients randomized, treated, having data for primary endpoint

Arm/Group Title	Pramipexole	Placebo
Arm/Group Description
Measure Participants	195	92
Least Squares Mean (Standard Error) [Score on a scale]	-15.87 (0.66)	-11.35 (0.92)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA with treatment and center as fixed factors and baseline as a covariate
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.52
	Confidence Interval	(2-Sided) 95%; -6.58 to -2.46
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.05
	Estimation Comments

2. Primary Outcome

Title	The Proportion of Patients With Clinical Global Impressions -Improvement Scale (CGI-I) Assessment of "Much Improved" and "Very Much Improved"
Description	CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved)and 2 (much improved.
Time Frame	6 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pramipexole	Placebo
Arm/Group Description
Measure Participants	193	92
Number [Proportion of Patients]	0.819	0.543

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	test stratified by centre

3. Secondary Outcome

Title	The Proportion of IRLS Responders
Description	responders is defined as the total score in IRLS changed ≥ 50%from baseline calculated in the full analysis set population.
Time Frame	6 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pramipexole	Placebo
Arm/Group Description
Measure Participants	195	92
Number [Proportion of Patients]	0.738	0.489

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	test stratified by centre

4. Secondary Outcome

Title	The Proportion of Patient Global Impression(PGI) Responders
Description	PGI was a one-question scale with 7 degrees to assess patient's overall condition, ranging from very much better to very much worse. The responder are defined as patients with their assessment of "much better" or "very much better".
Time Frame	6 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pramipexole	Placebo
Arm/Group Description
Measure Participants	194	92
Number [Proportion of participants]	0.686 0.3%	0.435 0.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	test stratified by centre

5. Secondary Outcome

Title	The Proportion of Patients With Epworth Sleepiness Scale (ESS) Categorised >10
Description	The ESS is a self-administered instrument to assess the patients likelihood of falling asleep in various activities of daily living; the maximum score is 24 indicating a very high level of daytime sleepiness and a high likelihood of falling asleep.
Time Frame	week 6 of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pramipexole	Placebo
Arm/Group Description
Measure Participants	194	92
Number [Proportion of Patients]	0.108	0.054

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1386
	Comments
	Method	Chi-squared
	Comments

6. Secondary Outcome

Title	the Mean Change From Baseline to Week 6 in Satisfaction of Sleep at Night of RLS-6 Rating Scales
Description	RLS-6 rating scales comprises 6 questions Satisfaction of sleep is one of the 6 questions. The patient should give a rate between 0 (none/Not at all) to 10 (very severe) for the satisfaction of sleep.
Time Frame	Baseline and 6 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pramipexole	Placebo
Arm/Group Description
Measure Participants	194	92
Mean (Standard Deviation) [Score on a scale]	-4.52 (0.21)	-3.04 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA with treatment and center as fixed factors and baseline as a covariate
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.48
	Confidence Interval	(2-Sided) 95%; -2.14 to -0.83
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.33
	Estimation Comments

7. Secondary Outcome

Title	The Mean Change From Baseline in the Severity of RLS at Time of Falling Sleep of RLS-6 Rating Scales.
Description	RLS-6 rating scales comprises 6 questions. The severity of RLS at time of falling sleep is one of the 6 questions. The patient should give a rate between 0 (none/Not at all) to 10 (very severe) for the severity of RLS at time of falling sleep
Time Frame	Baseline and 6 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pramipexole	Placebo
Arm/Group Description
Measure Participants	194	92
Mean (Standard Deviation) [Score on a scale]	-4.9 (0.21)	-3.53 (0.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA with treatment and center as fixed factors and baseline as a covariate
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.36
	Confidence Interval	(2-Sided) 95%; -1.99 to -0.73
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.32
	Estimation Comments

8. Secondary Outcome

Title	The Mean Change From Baseline in the Severity of RLS During the Night of RLS-6 Rating Scales.
Description	RLS-6 rating scales comprises 6 questions. The severity of RLS during the night is one of the 6 questions. The patient should give a rate between 0 ("none/Not at all") to 10 ("very severe") for the severity of RLS during the night.
Time Frame	Baseline and 6 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pramipexole	Placebo
Arm/Group Description
Measure Participants	194	92
Mean (Standard Deviation) [Score on a scale]	-4.68 (0.21)	-3.32 (0.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA with treatment and center as fixed factors and baseline as a covariate
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.36
	Confidence Interval	(2-Sided) 95%; -2.00 to -0.72
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.33
	Estimation Comments

9. Secondary Outcome

Title	The Mean Change From Baseline in the Severity of RLS During the Rest at Day of RLS-6 Rating Scales.
Description	RLS-6 rating scales comprises 6 questions. The severity of RLS during the test at day is one of the 6 questions. The patient should give a rate between 0 ("none/Not at all") to 10 ("very severe") for the severity of RLS during the rest at day.
Time Frame	Baseline and 6 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pramipexole	Placebo
Arm/Group Description
Measure Participants	194	92
Mean (Standard Deviation) [Score on a scale]	-2.9 (0.17)	-2.36 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0402
	Comments
	Method	ANCOVA
	Comments	ANCOVA with treatment and center as fixed factors and baseline as a covariate
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.54
	Confidence Interval	(2-Sided) 95%; -1.06 to -0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.26
	Estimation Comments

10. Secondary Outcome

Title	The Mean Change From Baseline in the Severity of RLS During the Activities at Day of RLS-6 Rating Scale
Description	RLS-6 rating scales comprises 6 questions. The severity of RLS during the activities at day is one of the 6 questions. The patient should give a rate between 0 ("none/Not at all") to 10 ("very severe") for the severity of RLS during the activity at day.
Time Frame	Baseline and 6 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pramipexole	Placebo
Arm/Group Description
Measure Participants	194	92
Mean (Standard Deviation) [Score on a scale]	-0.93 (0.12)	-0.61 (0.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0771
	Comments
	Method	ANCOVA
	Comments	ANCOVA with treatment and center as fixed factors and baseline as a covariate
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.33
	Confidence Interval	(2-Sided) 95%; -0.69 to 0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.18
	Estimation Comments

11. Secondary Outcome

Title	The Mean Change From Baseline in the Intensity of Tiredness and Sleepiness at Day of RLS-6 Rating Scale
Description	RLS-6 rating scales comprises 6 questions. The intensity of tiredness and sleepiness at day is one of the 6 questions. The patient should give a rate between 0 ("none/Not at all") to 10 ("very severe") for the intensity of tiredness and sleepiness at day.
Time Frame	Baseline and 6 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pramipexole	Placebo
Arm/Group Description
Measure Participants	194	92
Mean (Standard Deviation) [Score on a scale]	-2.96 (0.16)	-2.25 (0.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0048
	Comments
	Method	ANCOVA
	Comments	ANCOVA with treatment and center as fixed factors and baseline as a covariate
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.71
	Confidence Interval	(2-Sided) 95%; -1.20 to -0.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.25
	Estimation Comments

12. Secondary Outcome

Title	The Change From Baseline in Visual Analogue Scales (VAS)
Description	VAS is for assessment of RLS-associated pain. The patient was asked "How severe was your RLS associated pain in legs or arms during the past week?". No pain:0; very worst pain:10
Time Frame	Baseline and 6 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pramipexole	Placebo
Arm/Group Description
Measure Participants	194	92
Mean (Standard Deviation) [Score on a scale]	2.6 (2.5)	3.9 (3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA with treatment and center as fixed factors and baseline as a covariate

Adverse Events

Time Frame	6 Weeks
Arm/Group Title	Pramipexole		Placebo
Arm/Group Description
All Cause Mortality
	Pramipexole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Pramipexole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/202 (1.5%)		0/103 (0%)
Infections and infestations
Pneumonia	1/202 (0.5%)		0/103 (0%)
Injury, poisoning and procedural complications
Injury	1/202 (0.5%)		0/103 (0%)
Nervous system disorders
Transient ischaemic attack	1/202 (0.5%)		0/103 (0%)
Other (Not Including Serious) Adverse Events
	Pramipexole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	81/202 (40.1%)		25/103 (24.3%)
Gastrointestinal disorders
Nausea	26/202 (12.9%)		8/103 (7.8%)
Nervous system disorders
Dizziness	35/202 (17.3%)		9/103 (8.7%)
Headache	20/202 (9.9%)		2/103 (1.9%)
Somnolence	28/202 (13.9%)		9/103 (8.7%)
Psychiatric disorders
Insomnia	4/202 (2%)		6/103 (5.8%)

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.