Restless Legs Syndrome
Conditions
Keywords
Rotigotine, Neupro®, Augmentation, Restless Legs Syndrome, Moderate to severe, idiopathic, adults
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.
Interventions
None listed
Sponsors
UCB Pharma
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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: 1. = Normal, not ill at all 2. = Borderline ill 3. = Mildly ill 4. = Moderately ill 5. = Markedly ill 6. = Severely ill 7. = Among the most extremely ill subjects A negative change from Baseline to Visit 4 indicates an improvement in CGI Item 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: 1. = Normal, not ill at all 2. = Borderline ill 3. = Mildly ill 4. = Moderately ill 5. = Markedly ill 6. = Severely ill 7. = Among the most extremely ill subjects A negative change from Baseline to Visit 2 indicates an improvement in CGI Item 1. |
| 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: 1. = Normal, not ill at all 2. = Borderline ill 3. = Mildly ill 4. = Moderately ill 5. = Markedly ill 6. = Severely ill 7. = Among the most extremely ill subjects A negative change from Baseline to Visit 3 indicates an improvement in CGI Item 1. |
| 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: 1. = Normal, not ill at all 2. = Borderline ill 3. = Mildly ill 4. = Moderately ill 5. = Markedly ill 6. = Severely ill 7. = Among the most extremely ill subjects A negative change from Baseline to Visit 7 indicates an improvement in CGI Item 1. |
| 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: 1. = Normal, not ill at all 2. = Borderline ill 3. = Mildly ill 4. = Moderately ill 5. = Markedly ill 6. = Severely ill 7. = Among the most extremely ill subjects A negative change from Baseline to Visit 2 indicates an improvement in CGI Item 1. |
| 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: 1. = Normal, not ill at all 2. = Borderline ill 3. = Mildly ill 4. = Moderately ill 5. = Markedly ill 6. = Severely ill 7. = Among the most extremely ill subjects A negative change from Baseline to Visit 6 indicates an improvement in CGI Item 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Germany
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 details
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).
Participants by arm
| Arm | Count |
|---|---|
| Neupro® Treatment Routine treatment (1,2,3 mg/24 h) as per approved label in the European Union (EU). | 97 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 26 |
| Overall Study | Lack of Efficacy | 14 |
| Overall Study | Lost to Follow-up | 8 |
| Overall Study | Unspecified reason | 8 |
Baseline characteristics
| Characteristic | Neupro® Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 52 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants |
| Age, Continuous | 64.2 years STANDARD_DEVIATION 11.1 |
| Height | 168.43 centimeter STANDARD_DEVIATION 9.48 |
| Race/Ethnicity, Customized Missing | 2 participants |
| Race/Ethnicity, Customized Scandinavian/Central European | 90 participants |
| Race/Ethnicity, Customized Southern European | 5 participants |
| Sex: Female, Male Female | 66 Participants |
| Sex: Female, Male Male | 31 Participants |
| Weight | 81.69 kilogram STANDARD_DEVIATION 15.93 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 40 / 99 |
| serious Total, serious adverse events | 9 / 99 |
Outcome results
Primary
Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 2
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: 1. = Normal, not ill at all 2. = Borderline ill 3. = Mildly ill 4. = Moderately ill 5. = Markedly ill 6. = Severely ill 7. = 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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Neupro® Treatment | Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 2 | -0.8 score on a scale | Standard Deviation 1.1 |
95% CI: [-1, -0.5]
Primary
Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 3
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: 1. = Normal, not ill at all 2. = Borderline ill 3. = Mildly ill 4. = Moderately ill 5. = Markedly ill 6. = Severely ill 7. = 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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Neupro® Treatment | Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 3 | -1.4 score on a scale | Standard Deviation 1.3 |
95% CI: [-1.5, -1]
Primary
Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 4
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: 1. = Normal, not ill at all 2. = Borderline ill 3. = Mildly ill 4. = Moderately ill 5. = Markedly ill 6. = Severely ill 7. = 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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Neupro® Treatment | Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 4 | -1.8 score on a scale | Standard Deviation 1.2 |
95% CI: [-2, -1.5]
Primary
Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 5
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: 1. = Normal, not ill at all 2. = Borderline ill 3. = Mildly ill 4. = Moderately ill 5. = Markedly ill 6. = Severely ill 7. = 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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Neupro® Treatment | Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 5 | -2.0 score on a scale | Standard Deviation 1.4 |
95% CI: [-2.5, -1.5]
Primary
Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 6
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: 1. = Normal, not ill at all 2. = Borderline ill 3. = Mildly ill 4. = Moderately ill 5. = Markedly ill 6. = Severely ill 7. = 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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Neupro® Treatment | Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 6 | -2.0 score on a scale | Standard Deviation 1.3 |
95% CI: [-2.5, -1.5]
Primary
Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 7
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: 1. = Normal, not ill at all 2. = Borderline ill 3. = Mildly ill 4. = Moderately ill 5. = Markedly ill 6. = Severely ill 7. = 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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Neupro® Treatment | Change From Baseline (Visit 1) in Clinical Global Impression (CGI) (Item 1 - Severity of Illness) to Visit 7 | -1.8 score on a scale | Standard Deviation 1.3 |
95% CI: [-2, -1.5]
Secondary
Change in Treatment Regimen Used for Switching to Neupro® up to 28 Days After Entering in the Study
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Neupro® Treatment | Change in Treatment Regimen Used for Switching to Neupro® up to 28 Days After Entering in the Study | Switch after Drug holiday | 5 participants |
| Neupro® Treatment | Change in Treatment Regimen Used for Switching to Neupro® up to 28 Days After Entering in the Study | Overnight Switch | 23 participants |
| Neupro® Treatment | Change in Treatment Regimen Used for Switching to Neupro® up to 28 Days After Entering in the Study | Overlapping Switch | 9 participants |
| Neupro® Treatment | Change in Treatment Regimen Used for Switching to Neupro® up to 28 Days After Entering in the Study | No Switch | 6 participants |