Restless Legs Syndrome
Conditions
Brief summary
The objectives of the Post Market Surveillance (PMS) study are to evaluate the treatment effect of pramipexole on Restless Legs Syndrome (RLS) severity as measured by International Restless Legs Rating Scale and Global Clinical Impression - Improvement, to evaluate the time to reaching maintenance dose of pramipexole
Interventions
DRUGSifrol® (pramipexole dihydrochloride)
Sponsors
Boehringer Ingelheim
Study design
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Primary Restless Legs Syndrome (i.e. idiopathic RLS) * Indication for treatment with pramipexole * Male or female patients older than 18 years
Exclusion criteria
* Any contraindications according to the Summary of Product Characteristics (SPC): hypersensitivity to pramipexole or to any of the excipients * Current treatment with pramipexole
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency Analysis for Baseline Pattern of RLS Symptoms | Baseline | Severity of RLS was rated using the International RLS Severity Scale. This scale measures the severity of RLS symptoms and comprises of 10 questions with 5 possible answers, each answer scored from 0-4 points and is classified into 5 RLS severity groups: 0 points = no symptoms, 1-10 points = mild, 11-20 points = moderate, 21-30 points = severe, 31-40 points = very severe. |
| Change in Total Scores of IRLS (International Restless Legs Rating Scale) | Baseline and final visit (week12) | The International Restless Legs Syndrome Rating Scale (IRLS) is a rating scale used to assess the severity of RLS symptoms. The IRLS consists of 10 items, each of which is rated from 0 to 4 points, higher values denoting an increased severity of symptoms. Maximum total score is 40. Score totals are grouped into four levels of severity: 1-10 points = mild RLS, 11-20 points = moderate RLS, 21-30 points = severe RLS, and 31-40 = very severe RLS. The change from baseline was calculated as baseline minus the week 12 value. |
| Change in Global Clinical Impression - Improvement (CGI-I) Scale | baseline and final visit (week 12) | The Clinical Global Impression Improvement scale (CGI-I) requires the clinician to rate how much the patient's illness has improved or worsened relative to a baseline state. A patient's illness is compared to change over time and rated as: very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse |
| Frequency of Adverse Events | Up to 16 weeks | Frequency of patients with any adverse event, causally related adverse events and serious adverse events |
| Correlation of the Change in IRLS at End of Titration and at Final Visit | Up to 12 weeks | Correlation of the change in IRLS at end of titration and at final visit |
Countries
Austria
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| De-novo Patients Patients that had not been treated for RLS at baseline | 452 |
| Pre-treated Patients Patients that had been treated for RLS at baseline | 97 |
| Total | 549 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 6 | 3 |
| Overall Study | Other | 12 | 16 |
| Overall Study | Tolerability insufficient | 5 | 2 |
| Overall Study | Withdrawal by Subject | 13 | 3 |
Baseline characteristics
| Characteristic | De-novo Patients | Pre-treated Patients | Total |
|---|---|---|---|
| Age, Continuous | 66.48 years STANDARD_DEVIATION 12.87 | 67.81 years STANDARD_DEVIATION 12.61 | 66.69 years STANDARD_DEVIATION 12.82 |
| Sex/Gender, Customized Female | 317 participants | 66 participants | 383 participants |
| Sex/Gender, Customized Male | 131 participants | 23 participants | 154 participants |
| Sex/Gender, Customized missing | 4 participants | 8 participants | 12 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 452 | 0 / 97 |
| serious Total, serious adverse events | 0 / 452 | 2 / 97 |
Outcome results
Primary
Change in Global Clinical Impression - Improvement (CGI-I) Scale
The Clinical Global Impression Improvement scale (CGI-I) requires the clinician to rate how much the patient's illness has improved or worsened relative to a baseline state. A patient's illness is compared to change over time and rated as: very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse
Time frame: baseline and final visit (week 12)
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| De-novo Patients | Change in Global Clinical Impression - Improvement (CGI-I) Scale | Very much improved | 47.0 percentage of participants |
| De-novo Patients | Change in Global Clinical Impression - Improvement (CGI-I) Scale | Much improved | 45.5 percentage of participants |
| De-novo Patients | Change in Global Clinical Impression - Improvement (CGI-I) Scale | Minimally improved | 3.0 percentage of participants |
| De-novo Patients | Change in Global Clinical Impression - Improvement (CGI-I) Scale | No change | 1.8 percentage of participants |
| De-novo Patients | Change in Global Clinical Impression - Improvement (CGI-I) Scale | Minimally worse | 0.0 percentage of participants |
| De-novo Patients | Change in Global Clinical Impression - Improvement (CGI-I) Scale | Much worse | 0.2 percentage of participants |
| De-novo Patients | Change in Global Clinical Impression - Improvement (CGI-I) Scale | Very much worse | 0.0 percentage of participants |
| De-novo Patients | Change in Global Clinical Impression - Improvement (CGI-I) Scale | missing | 2.5 percentage of participants |
| Pre-treated Patients | Change in Global Clinical Impression - Improvement (CGI-I) Scale | missing | 2.4 percentage of participants |
| Pre-treated Patients | Change in Global Clinical Impression - Improvement (CGI-I) Scale | Very much improved | 44.6 percentage of participants |
| Pre-treated Patients | Change in Global Clinical Impression - Improvement (CGI-I) Scale | Minimally worse | 0.0 percentage of participants |
| Pre-treated Patients | Change in Global Clinical Impression - Improvement (CGI-I) Scale | Much improved | 42.2 percentage of participants |
| Pre-treated Patients | Change in Global Clinical Impression - Improvement (CGI-I) Scale | Very much worse | 0.0 percentage of participants |
| Pre-treated Patients | Change in Global Clinical Impression - Improvement (CGI-I) Scale | Minimally improved | 8.4 percentage of participants |
| Pre-treated Patients | Change in Global Clinical Impression - Improvement (CGI-I) Scale | Much worse | 0.0 percentage of participants |
| Pre-treated Patients | Change in Global Clinical Impression - Improvement (CGI-I) Scale | No change | 2.4 percentage of participants |
Primary
Change in Total Scores of IRLS (International Restless Legs Rating Scale)
The International Restless Legs Syndrome Rating Scale (IRLS) is a rating scale used to assess the severity of RLS symptoms. The IRLS consists of 10 items, each of which is rated from 0 to 4 points, higher values denoting an increased severity of symptoms. Maximum total score is 40. Score totals are grouped into four levels of severity: 1-10 points = mild RLS, 11-20 points = moderate RLS, 21-30 points = severe RLS, and 31-40 = very severe RLS. The change from baseline was calculated as baseline minus the week 12 value.
Time frame: Baseline and final visit (week12)
Population: Only those patients of the full analysis set with an evaluation of the IRLS at visit 3 were included
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| De-novo Patients | Change in Total Scores of IRLS (International Restless Legs Rating Scale) | 17 scores on a scale |
| Pre-treated Patients | Change in Total Scores of IRLS (International Restless Legs Rating Scale) | 16 scores on a scale |
Primary
Correlation of the Change in IRLS at End of Titration and at Final Visit
Correlation of the change in IRLS at end of titration and at final visit
Time frame: Up to 12 weeks
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| De-novo Patients | Correlation of the Change in IRLS at End of Titration and at Final Visit | End of titration - Deterioration (n=517) | 0.0 percentage of patients |
| De-novo Patients | Correlation of the Change in IRLS at End of Titration and at Final Visit | End of titration - No change (n=517) | 19.7 percentage of patients |
| De-novo Patients | Correlation of the Change in IRLS at End of Titration and at Final Visit | End of titration - Improvement (n=517) | 80.3 percentage of patients |
| De-novo Patients | Correlation of the Change in IRLS at End of Titration and at Final Visit | Final Visit - Deterioration | 0.2 percentage of patients |
| De-novo Patients | Correlation of the Change in IRLS at End of Titration and at Final Visit | Final Visit - No change | 5.4 percentage of patients |
| De-novo Patients | Correlation of the Change in IRLS at End of Titration and at Final Visit | Final Visit - Improvement | 94.5 percentage of patients |
Primary
Frequency Analysis for Baseline Pattern of RLS Symptoms
Severity of RLS was rated using the International RLS Severity Scale. This scale measures the severity of RLS symptoms and comprises of 10 questions with 5 possible answers, each answer scored from 0-4 points and is classified into 5 RLS severity groups: 0 points = no symptoms, 1-10 points = mild, 11-20 points = moderate, 21-30 points = severe, 31-40 points = very severe.
Time frame: Baseline
Population: Full analysis set (FAS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| De-novo Patients | Frequency Analysis for Baseline Pattern of RLS Symptoms | Mild | 0.7 percentage of participants |
| De-novo Patients | Frequency Analysis for Baseline Pattern of RLS Symptoms | Moderate | 19.3 percentage of participants |
| De-novo Patients | Frequency Analysis for Baseline Pattern of RLS Symptoms | Severe | 62.0 percentage of participants |
| De-novo Patients | Frequency Analysis for Baseline Pattern of RLS Symptoms | Very Severe | 18.0 percentage of participants |
| Pre-treated Patients | Frequency Analysis for Baseline Pattern of RLS Symptoms | Very Severe | 24.1 percentage of participants |
| Pre-treated Patients | Frequency Analysis for Baseline Pattern of RLS Symptoms | Mild | 2.4 percentage of participants |
| Pre-treated Patients | Frequency Analysis for Baseline Pattern of RLS Symptoms | Severe | 55.4 percentage of participants |
| Pre-treated Patients | Frequency Analysis for Baseline Pattern of RLS Symptoms | Moderate | 18.1 percentage of participants |
Primary
Frequency of Adverse Events
Frequency of patients with any adverse event, causally related adverse events and serious adverse events
Time frame: Up to 16 weeks
Population: Safety Analysis Set (SAF)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| De-novo Patients | Frequency of Adverse Events | Any adverse event | 25 participants |
| De-novo Patients | Frequency of Adverse Events | Causally related adverse event | 7 participants |
| De-novo Patients | Frequency of Adverse Events | serious adverse events | 2 participants |