AURORA: Effect on RLS Symptom Severity After Switching to Neupro® in Patients Who Previously Experienced Augmentation

• Sponsor: UCB Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01386944
• Collaborator: (none)
• Enrollment: 102
• Locations: 18
• Duration (Months): 25
• Patients Per Site: 5.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The objective is to assess the effect of Neupro® on the severity of Restless Leg Syndrome (RLS) symptoms and augmentation in patients with augmentation associated with previous oral dopaminergic therapy. In addition, the change in treatment regimen used when switching to Neupro® will be evaluated.

Condition or Disease	Intervention/Treatment	Phase
Restless Legs Syndrome

Study Design

• Study Type: Observational
• Actual Enrollment: 102 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Non Interventional Observational Study to Collect Data for the Effect of Switching to Neupro® on Severity of Restless Leg Syndrome (RLS) Symptoms and Augmentation as Well as the Change in Treatment Regimen Used, in RLS Patients With Previous Augmentation
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Aug 1, 2013
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Neupro® Treatment Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).

Outcome Measures

Primary Outcome Measures

1. Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 2 [From Baseline up to 7 days]

   The CGI scales document a global assessment of the severity of RLS at single visits according to the treating physician. To this end the physician judges severity of disease by following a simple seven step severity rating scale: = Normal, not ill at all = Borderline ill = Mildly ill = Moderately ill = Markedly ill = Severely ill = Among the most extremely ill subjects A negative change from Baseline to Visit 2 indicates an improvement in CGI Item 1.

2. Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 3 [From Baseline up to 28 days]

   The CGI scales document a global assessment of the severity of RLS at single visits according to the treating physician. To this end the physician judges severity of disease by following a simple seven step severity rating scale: = Normal, not ill at all = Borderline ill = Mildly ill = Moderately ill = Markedly ill = Severely ill = Among the most extremely ill subjects A negative change from Baseline to Visit 3 indicates an improvement in CGI Item 1.

3. Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 4 [From Baseline up to 4 months]

   The CGI scales document a global assessment of the severity of RLS at single visits according to the treating physician. To this end the physician judges severity of disease by following a simple seven step severity rating scale: = Normal, not ill at all = Borderline ill = Mildly ill = Moderately ill = Markedly ill = Severely ill = Among the most extremely ill subjects A negative change from Baseline to Visit 4 indicates an improvement in CGI Item 1.

4. Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 5 [From Baseline up to 7 months]

   The CGI scales document a global assessment of the severity of RLS at single visits according to the treating physician. To this end the physician judges severity of disease by following a simple seven step severity rating scale: = Normal, not ill at all = Borderline ill = Mildly ill = Moderately ill = Markedly ill = Severely ill = Among the most extremely ill subjects A negative change from Baseline to Visit 2 indicates an improvement in CGI Item 1.

5. Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 6 [From Baseline up to 10 months]

   The CGI scales document a global assessment of the severity of RLS at single visits according to the treating physician. To this end the physician judges severity of disease by following a simple seven step severity rating scale: = Normal, not ill at all = Borderline ill = Mildly ill = Moderately ill = Markedly ill = Severely ill = Among the most extremely ill subjects A negative change from Baseline to Visit 6 indicates an improvement in CGI Item 1.

6. Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 7 [From Baseline up to 13 months]

   The CGI scales document a global assessment of the severity of RLS at single visits according to the treating physician. To this end the physician judges severity of disease by following a simple seven step severity rating scale: = Normal, not ill at all = Borderline ill = Mildly ill = Moderately ill = Markedly ill = Severely ill = Among the most extremely ill subjects A negative change from Baseline to Visit 7 indicates an improvement in CGI Item 1.

Secondary Outcome Measures

1. Change in Treatment Regimen Used for Switching to Neupro® up to 28 Days After Entering in the Study [From Baseline up to 28 days]

   Case reports from clinical practice refer to different switching regimens for patients taking oral dopaminergics who experienced augmentation and then switched to Neupro®. The previous dopaminergic treatment might have been partly or completely down-titrated prior to switching to Neupro®. Physicians were requested to document the change of treatment at each recommended visit in the electronic Case Report Form (eCRF) considering their total clinical experience with this particular Restless Legs Syndrome (RLS) patients population. Documentation comprised changes in the RLS medication last prescribed, and the dosage of Neupro® and concomitant medications. The change of treatment regimen was entirely at the physicians' discretion.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The adult patient has a diagnosis of moderate to severe idiopathic Restless Leg Syndrome (RLS)

• The patient must be experiencing augmentation due to a prior dopaminergic treatment

• The decision to prescribe Neupro® has been made by the physician independently of his/her decision to enroll the patient in the study

• Patient is informed and given ample time and opportunity to think about his/her participation in the study and has given written informed data consent

Exclusion Criteria:

• Patients diagnosed with secondary Restless Leg Syndrome (RLS) should not be enrolled in this observational study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	12	Berlin		Germany
2	4	Bremen		Germany
3	18	Dresden		Germany
4	20	Flensburg		Germany
5	1	Kassel		Germany
6	11	Marburg		Germany
7	17	Marburg		Germany
8	2	Mönchengladbach		Germany
9	6	Münster		Germany
10	7	Regensburg		Germany
11	21	Remscheid		Germany
12	15	Schriesheim		Germany
13	10	Schwalmstadt		Germany
14	3	Schwerin		Germany
15	8	Tuebingen		Germany
16	16	Ulm		Germany
17	9	Ulm		Germany
18	19	Westerstede		Germany

Sponsors and Collaborators

• UCB Pharma

Investigators

• Study Director: UCB Clinical Trial Call Center, [phone] (UCB)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: UCB Pharma
• ClinicalTrials.gov Identifier: NCT01386944
• Other Study ID Numbers: SP1009
• First Posted: Jul 1, 2011
• Last Update Posted: Apr 4, 2018
• Last Verified: Mar 1, 2018

• Keywords provided by UCB Pharma: Rotigotine; Neupro®; Augmentation; Restless Legs Syndrome; Moderate to severe; idiopathic; adults
• Additional relevant MeSH terms: Psychomotor Agitation; Restless Legs Syndrome; Syndrome

Study Results

Participant Flow

Recruitment Details	This non-interventional study (NIS) was conducted in 18 specialized centres (medical practice and outpatient department) for neurology throughout Germany. The Participant Flow refers to the Enrolled Set (ES). The ES consists of all patients who provided informed consent.
Pre-assignment Detail	The physician was to decide freely to treat the patient with Neupro®. In this context, the physician was not to change routine practice in reaching treatment decisions and in treating his/her patients because of the study. The observational period was 13 months per patient (adjustment period of medication switch plus 12 months of observation).

Arm/Group Title	Neupro® Treatment
Arm/Group Description	Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Period Title: Overall Study
STARTED	102
COMPLETED	46
NOT COMPLETED	56

Baseline Characteristics

Arm/Group Title	Neupro® Treatment
Arm/Group Description	Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Overall Participants	97
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.2 (11.1)
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	45 46.4%
>=65 years	52 53.6%
Sex: Female, Male (Count of Participants)
Female	66 68%
Male	31 32%
Race/Ethnicity, Customized (participants) [Number]
Scandinavian/Central European	90 92.8%
Southern European	5 5.2%
Missing	2 2.1%
Height (centimeter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter]	168.43 (9.48)
Weight (kilogram) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram]	81.69 (15.93)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 2
Description	The CGI scales document a global assessment of the severity of RLS at single visits according to the treating physician. To this end the physician judges severity of disease by following a simple seven step severity rating scale: = Normal, not ill at all = Borderline ill = Mildly ill = Moderately ill = Markedly ill = Severely ill = Among the most extremely ill subjects A negative change from Baseline to Visit 2 indicates an improvement in CGI Item 1.
Time Frame	From Baseline up to 7 days

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Full Analysis Set (FAS). The FAS is a subset of the Safety Set and consists of all patients who received treatment with Neupro at least once and had a Visit 1 and at least one post-Visit 1 measurement on the primary variable documented.

Arm/Group Title	Neupro® Treatment
Arm/Group Description	Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Measure Participants	89
Mean (Standard Deviation) [score on a scale]	-0.8 (1.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neupro® Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehmann Estimate
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.0 to -0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 3
Description	The CGI scales document a global assessment of the severity of RLS at single visits according to the treating physician. To this end the physician judges severity of disease by following a simple seven step severity rating scale: = Normal, not ill at all = Borderline ill = Mildly ill = Moderately ill = Markedly ill = Severely ill = Among the most extremely ill subjects A negative change from Baseline to Visit 3 indicates an improvement in CGI Item 1.
Time Frame	From Baseline up to 28 days

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Full Analysis Set (FAS). The FAS is a subset of the Safety Set and consists of all patients who received treatment with Neupro at least once and had a Visit 1 and at least one post-Visit 1 measurement on the primary variable documented.

Arm/Group Title	Neupro® Treatment
Arm/Group Description	Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Measure Participants	77
Mean (Standard Deviation) [score on a scale]	-1.4 (1.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neupro® Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehmann Estimate
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -1.5 to -1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 4
Description	The CGI scales document a global assessment of the severity of RLS at single visits according to the treating physician. To this end the physician judges severity of disease by following a simple seven step severity rating scale: = Normal, not ill at all = Borderline ill = Mildly ill = Moderately ill = Markedly ill = Severely ill = Among the most extremely ill subjects A negative change from Baseline to Visit 4 indicates an improvement in CGI Item 1.
Time Frame	From Baseline up to 4 months

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Full Analysis Set (FAS). The FAS is a subset of the Safety Set and consists of all patients who received treatment with Neupro at least once and had a Visit 1 and at least one post-Visit 1 measurement on the primary variable documented.

Arm/Group Title	Neupro® Treatment
Arm/Group Description	Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Measure Participants	58
Mean (Standard Deviation) [score on a scale]	-1.8 (1.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neupro® Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehmann Estimate
	Estimated Value	-2.0
	Confidence Interval	() 95%; -2.0 to -1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 5
Description	The CGI scales document a global assessment of the severity of RLS at single visits according to the treating physician. To this end the physician judges severity of disease by following a simple seven step severity rating scale: = Normal, not ill at all = Borderline ill = Mildly ill = Moderately ill = Markedly ill = Severely ill = Among the most extremely ill subjects A negative change from Baseline to Visit 2 indicates an improvement in CGI Item 1.
Time Frame	From Baseline up to 7 months

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Full Analysis Set (FAS). The FAS is a subset of the Safety Set and consists of all patients who received treatment with Neupro at least once and had a Visit 1 and at least one post-Visit 1 measurement on the primary variable documented.

Arm/Group Title	Neupro® Treatment
Arm/Group Description	Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Measure Participants	52
Mean (Standard Deviation) [score on a scale]	-2.0 (1.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neupro® Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehmann Estimate
	Estimated Value	-2.0
	Confidence Interval	() 95%; -2.5 to -1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 6
Description	The CGI scales document a global assessment of the severity of RLS at single visits according to the treating physician. To this end the physician judges severity of disease by following a simple seven step severity rating scale: = Normal, not ill at all = Borderline ill = Mildly ill = Moderately ill = Markedly ill = Severely ill = Among the most extremely ill subjects A negative change from Baseline to Visit 6 indicates an improvement in CGI Item 1.
Time Frame	From Baseline up to 10 months

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Full Analysis Set (FAS). The FAS is a subset of the Safety Set and consists of all patients who received treatment with Neupro at least once and had a Visit 1 and at least one post-Visit 1 measurement on the primary variable documented.

Arm/Group Title	Neupro® Treatment
Arm/Group Description	Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Measure Participants	45
Mean (Standard Deviation) [score on a scale]	-2.0 (1.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neupro® Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehmann Estimate
	Estimated Value	-2.0
	Confidence Interval	() 95%; -2.5 to -1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Primary Outcome

Title	Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 7
Description	The CGI scales document a global assessment of the severity of RLS at single visits according to the treating physician. To this end the physician judges severity of disease by following a simple seven step severity rating scale: = Normal, not ill at all = Borderline ill = Mildly ill = Moderately ill = Markedly ill = Severely ill = Among the most extremely ill subjects A negative change from Baseline to Visit 7 indicates an improvement in CGI Item 1.
Time Frame	From Baseline up to 13 months

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Full Analysis Set (FAS). The FAS is a subset of the Safety Set and consists of all patients who received treatment with Neupro at least once and had a Visit 1 and at least one post-Visit 1 measurement on the primary variable documented.

Arm/Group Title	Neupro® Treatment
Arm/Group Description	Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Measure Participants	46
Mean (Standard Deviation) [score on a scale]	-1.8 (1.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Neupro® Treatment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehmann Estimate
	Estimated Value	-2.0
	Confidence Interval	() 95%; -2.0 to -1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change in Treatment Regimen Used for Switching to Neupro® up to 28 Days After Entering in the Study
Description	Case reports from clinical practice refer to different switching regimens for patients taking oral dopaminergics who experienced augmentation and then switched to Neupro®. The previous dopaminergic treatment might have been partly or completely down-titrated prior to switching to Neupro®. Physicians were requested to document the change of treatment at each recommended visit in the electronic Case Report Form (eCRF) considering their total clinical experience with this particular Restless Legs Syndrome (RLS) patients population. Documentation comprised changes in the RLS medication last prescribed, and the dosage of Neupro® and concomitant medications. The change of treatment regimen was entirely at the physicians' discretion.
Time Frame	From Baseline up to 28 days

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Eligibility Completer Set (ECS). The ECS is a subset of the Completer Set excluding patients with Parkinson's disease and/or treated Polyneuropathy as concomitant disease identified by the preferred term (PT) of the MedDRA coding and patients treated with Neupro up to 4 weeks before Visit 1.

Arm/Group Title	Neupro® Treatment
Arm/Group Description	Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
Measure Participants	43
Switch after "Drug holiday"	5 5.2%
Overnight Switch	23 23.7%
Overlapping Switch	9 9.3%
No Switch	6 6.2%

Adverse Events

Time Frame	Adverse Events were reported from Day 1 up to 13 months.
Adverse Event Reporting Description	The Analysis Population refers to the Safety Set (SS). The Safety Set (SS) consists of all patients who have signed the consent form and who received treatment with Neupro at least once. Every Adverse Event occurring during the conduct of the study had to be entered in the respective electronic AE/SAE documentation form irrespective of causality.
Arm/Group Title	Neupro® Treatment
Arm/Group Description	Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU).
All Cause Mortality
	Neupro® Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Neupro® Treatment
	Affected / at Risk (%)	# Events
Total	9/99 (9.1%)
Gastrointestinal disorders
Hiatus hernia	1/99 (1%)	1
Diverticulum	1/99 (1%)	1
Gastrointestinal haemorrhage	1/99 (1%)	1
Acquired oesophageal web	1/99 (1%)	1
General disorders
Irritability	1/99 (1%)	1
Infections and infestations
Pneumonia	1/99 (1%)	1
Urinary tract infection	1/99 (1%)	1
Metabolism and nutrition disorders
Hypokalaemia	1/99 (1%)	1
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome	1/99 (1%)	1
Osteoarthritis	1/99 (1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	2/99 (2%)	2
Malignant melanoma	1/99 (1%)	1
Psychiatric disorders
Depression	2/99 (2%)	2
Personality change	1/99 (1%)	1
Acute stress disorder	1/99 (1%)	1
Thinking abnormal	1/99 (1%)	1
Renal and urinary disorders
Micturition urgency	1/99 (1%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary fibrosis	1/99 (1%)	1
Respiratory failure	1/99 (1%)	1
Surgical and medical procedures
Thyroidectomy	1/99 (1%)	1
Vascular disorders
Arterial thrombosis limb	1/99 (1%)	1
Other (Not Including Serious) Adverse Events
	Neupro® Treatment
	Affected / at Risk (%)	# Events
Total	40/99 (40.4%)
Gastrointestinal disorders
Nausea	13/99 (13.1%)	15
General disorders
Application site erythema	15/99 (15.2%)	17
Application site reaction	9/99 (9.1%)	9
Application site pruritus	8/99 (8.1%)	8
Fatigue	9/99 (9.1%)	9
Nervous system disorders
Headache	6/99 (6.1%)	6
Psychiatric disorders
Depression	5/99 (5.1%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.