Restless Legs Syndrome
Conditions
Brief summary
The primary objective of the current study will be the evaluation of long-term efficacy of a 26-weeks treatment with pramipexole in patients with idiopathic moderate to severe Restless Legs Syndrome (RLS) in comparison to placebo. The key secondary objectives are to assess the effects on clinical global impressions - global improvement (CGI-I) (based on CGI-I responder rate) and on RLS (based on IRLS responder rate) for 26 weeks under pramipexole in comparison to placebo. Further secondary objectives are to investigate the incidence and severity of augmentation and rebound and to assess the effects on patient global impression (PGI) (based on PGI responder rate), on RLS symptoms (based on the RLS-6 scales), on associated mood disturbance (based on item 10 of the IRLS), on pain in limbs (based on a visual analogue scale (VAS)), on quality of life in RLS (based on Johns Hopkins RLS-QoL), on general quality of life Short Form 36 (SF-36) and on safety (based on adverse events (AE) profile) of pramipexole in comparison to placebo.
Interventions
DRUGPramipexole
DRUGPlacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Written informed consent consistent with International Conference on Harmonization - Good Clinical Practice (ICH-GCP) and local Institutional Review Board/Independent Ethics Committee (IRB/IEC) requirements obtained prior to any study procedures being performed and the ability and willingness to comply with study treatment regimen and to attend study assessments 2. Male or female out-patients aged 18-85 years 3. Diagnosis of idiopathic RLS according to the clinical RLS criteria of the International Restless Legs Syndrome Study Group (IRLSSG) \[P03-03355\]. All four criteria must be present to fulfil the diagnosis of RLS. 4. RLS symptoms present at least 2 to 3 days per week during the last 3 months prior to baseline (Visit 2) 5. IRLS total score \>15 at baseline (Visit 2)
Exclusion criteria
1. Women of child-bearing potential (i.e. premenopausal women, or postmenopausal women less than 6 months after last menses) who do not use during the clinical trial an adequate method of contraception such as: double barrier protection (e.g. diaphragm or condom and spermicide), intrauterine device, hormonal therapy (oral, injectable, or subcutaneous), or partner's surgical sterilization 2. Any woman of child-bearing potential not having a negative pregnancy test at screening 3. Breastfeeding women 4. Patients with known hypersensitivity to pramipexole or any other component of the investigational product or placebo tablets 5. Diagnosis of augmentation under previous pharmacological RLS treatment 6. Concomitant or previous pharmacologic therapy as follows: Any intake of dopamine agonists within 14 days prior to baseline (Visit 2); Any intake of levodopa within 14 days prior to baseline (Visit 2); Unsuccessful prior treatment with non-ergot dopamine agonists (e.g. pramipexole, ropinirole);
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Total Score After 26 Weeks | Baseline and 26 weeks | IRLS total score ranging from 0 (no RLS symptoms) to 40 (very severe RLS symptoms) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| International Restless Legs Syndrome (IRLS) Study Group Rating Scale Responder Rate | after 26 weeks of treatment | IRLS response was defined as at least 50% reduction in IRLS total score from baseline. IRLS total score ranging from 0 (no RLS symptoms) to 40 (very severe symptoms) |
| Patient Global Impression (PGI) Responder Rate | after 26 weeks of treatment | PGI scores ranging from '1' (very much better) to '7' (very much worse), PGI responder have scoring 1 or 2 (at least much better) |
| Change From Baseline in Restless Legs Syndrome-6 (RLS-6) Score Satisfaction With Sleep After 26 Weeks | baseline and 26 weeks of treatment | The score is an 11-point Likert scale, ranging from none/not at all (0) to very severe (10), to reflect the patient's condition during the previous week |
| Change From Baseline in RLS-6 Score Severity Falling Asleep After 26 Weeks | Baseline and 26 weeks of treatment | The score is an 11-point Likert scale, ranging from none/not at all (0) to very severe (10), to reflect the patient's condition during the previous week |
| Change From Baseline in RLS-6 Score Severity During the Night After 26 Weeks | baseline and 26 weeks of treatment | The question was rated on an 11-point Likert scale, ranging from none/not at all (0) to very severe (10), to reflect the patient's condition during the previous week |
| Change From Baseline in RLS-6 Score Severity During the Day When at Rest After 26 Weeks | Baseline and 26 weeks of treatment | The score is an 11-point Likert scale, ranging from none/not at all (0) to very severe (10), to reflect the patient's condition during the previous week |
| Change From Baseline RLS-6 Score Severity During the Day Engaged in Activities After 26 Weeks | Baseline and 26 weeks of treatment | The score is an 11-point Likert scale, ranging from none/not at all (0) to very severe (10), to reflect the patient's condition during the previous week |
| Change From Baseline in RLS-6 Score Tired or Sleepy During the Day After 26 Weeks | Baseline and 26 weeks of treatment | The score is an 11-point Likert scale, ranging from none/not at all (0) to very severe (10), to reflect the patient's condition during the previous week |
| Change From Baseline in IRLS Mood Disturbance Score (Item 10) After 26 Weeks | Baseline and 26 weeks of treatment | Mood disturbance associated with RLS symptoms ranging from 0 (none) to 4 (very severe) |
| Change From Baseline in Visual Analogue Scale (VAS) Score for Pain in Limbs After 26 Weeks | Baseline and 26 weeks of treatment | The scale measures pain on a continuous 100 mm axis ranging from no pain (0 mm) to unbearable pain (100 mm) |
| Change From Baseline in Quality of Life in RLS (RLS QoL) Score After 26 Weeks | Baseline and 26 weeks of treatment | RLS QoL total score ranging from 0 to 100 with higher values indicating better quality of life |
| Change From Baseline in Short Form-36 (SF-36) Dimension Bodily Pain After 26 Weeks | Baseline and 26 weeks | Score ranging from 0 to 100 with higher scores indicating less bodily pain |
| Change From Baseline in SF-36 Dimension General Health After 26 Weeks | Baseline and 26 weeks | Score ranging from 0 to 100 with higher scores indicating better health status |
| Change From Baseline in SF-36 Dimension Mental Health After 26 Weeks | Baseline and 26 weeks | Score ranging from 0 to 100 with higher scores indicating better mental health |
| Clinical Global Impression - Global Improvement (CGI-I) Responder Rate | after 26 weeks of treatment | CGI-I scores ranging from '1' (very much improved) to '7' (very much worse), CGI-I responder have scoring 1 or 2 (at least much improved) |
| Change From Baseline in SF-36 Dimension Role Limitations Due to Emotional Problems After 26 Weeks | Baseline and 26 weeks | Score ranging from 0 to 100 with higher scores indicating less limitations due to emotional problems |
| Change From Baseline in SF-36 Dimension Role Limitations Due to Physical Problems After 26 Weeks | Baseline and 26 weeks | Score ranging from 0 to 100 with higher scores indicating less limitations due to physical problems |
| Change From Baseline in SF-36 Dimension Social Functioning After 26 Weeks | Baseline and 26 weeks | Score ranging from 0 to 100 with higher scores indicating better social functioning |
| Change From Baseline in SF-36 Dimension Vitality After 26 Weeks | Baseline and 26 weeks | Score ranging from 0 to 100 with higher scores indicating better vitality |
| Change From Baseline in SF-36 Dimension Mental Component Summary After 26 Weeks | Baseline and 26 weeks | Score ranging from 0 to 100 with higher scores indicating better health |
| Change From Baseline in SF-36 Dimension Physical Component Summary After 26 Weeks | Baseline and 26 weeks | Score ranging from 0 to 100 with higher scores indicating better health |
| Diagnosis of Classified Augmentation According to Independent Expert Panel | after at least 4 weeks of treatment | Augmentation is a worsening of RLS symptoms and may manifest as increased severity and the involvement of other extremities or as a shift of RLS symptoms to a time period that is 2 or more hours earlier than was typical of the time of symptom onset during the initial course of beneficial stable treatment or the state before recently starting treatment. |
| Worsening of RLS Symptoms (by at Least 4 Points in the IRLS Total Score Compared to Baseline) After Treatment Discontinuation | after at least 1 week of treatment discontinuation | Worsening of RLS symptoms, in comparison to baseline, following abrupt treatment discontinuation (for patients with no added RLS therapy after study drug discontinuation). Assessment of worsening of RLS was based on the IRLS total score assessed 7 ± 1 days after treatment discontinuation (the end of the study or premature discontinuation) compared with that at baseline. Analysis considered the number of patients experiencing a clinically relevant deterioration of ≥4 points in total IRLS score 7 ± 1 days after discontinuation of trial medication compared with baseline. |
| Baseline, Week 26 Mean Supine Systolic Blood Pressure | Baseline, Week 26 | — |
| Baseline, Week 26 Mean Standing Systolic Blood Pressure | Baseline, Week 26 | — |
| Baseline, Week 26 Mean Supine Diastolic Blood Pressure | Baseline, Week 26 | — |
| Baseline, Week 26 Mean Standing Diastolic Blood Pressure | Baseline, Week 26 | — |
| Baseline, Week 26 Mean Supine Pulse Rate | Baseline, Week 26 | — |
| Baseline, Week 26 Mean Standing Pulse Rate | Baseline, Week 26 | — |
| Change From Baseline in SF-36 Dimension Physical Functioning After 26 Weeks | Baseline and 26 weeks | Score ranging from 0 to 100 with higher scores indicating better physical functioning |
Countries
Austria, Belgium, Finland, Germany, Ireland, Netherlands, Slovakia, Spain, United Kingdom
Participant flow
Pre-assignment details
Of 331 patients enrolled, 329 were treated with study drug. Two patients were randomized, but before their first intake of trial medication they decided to not participate in the study.
Participants by arm
| Arm | Count |
|---|---|
| Pramipexole 4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets | 166 |
| Placebo 4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets | 163 |
| Total | 329 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 19 | 23 |
| Overall Study | Lack of Efficacy | 4 | 25 |
| Overall Study | Lost to Follow-up | 2 | 4 |
| Overall Study | patient was asymptomatic | 1 | 0 |
| Overall Study | personal reason | 0 | 1 |
| Overall Study | Protocol Violation | 3 | 2 |
| Overall Study | Withdrawal by Subject | 6 | 5 |
Baseline characteristics
| Characteristic | Pramipexole | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 57.9 years STANDARD_DEVIATION 12.7 | 55.8 years STANDARD_DEVIATION 11.4 | 56.8 years STANDARD_DEVIATION 12.1 |
| Sex: Female, Male Female | 102 Participants | 94 Participants | 196 Participants |
| Sex: Female, Male Male | 64 Participants | 69 Participants | 133 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 70 / 166 | 58 / 163 |
| serious Total, serious adverse events | 8 / 166 | 3 / 163 |
Outcome results
Primary
Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Total Score After 26 Weeks
IRLS total score ranging from 0 (no RLS symptoms) to 40 (very severe RLS symptoms)
Time frame: Baseline and 26 weeks
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pramipexole | Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Total Score After 26 Weeks | -13.7 Scores on a scale | Standard Error 0.8 |
| Placebo | Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Total Score After 26 Weeks | -11.1 Scores on a scale | Standard Error 0.8 |
Comparison: Analysis of covariance for changes from baseline with factors treatment and country and using baseline as covariatep-value: 0.007795% CI: [-4.6, -0.7]ANCOVA
Secondary
Baseline, Week 26 Mean Standing Diastolic Blood Pressure
Time frame: Baseline, Week 26
Population: Treated Set, all patients who were documented to have taken at least one dose of study medication
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pramipexole | Baseline, Week 26 Mean Standing Diastolic Blood Pressure | Baseline | 82.7 mm Hg | Standard Deviation 10.5 |
| Pramipexole | Baseline, Week 26 Mean Standing Diastolic Blood Pressure | Week 26 | 80.5 mm Hg | Standard Deviation 10.6 |
| Placebo | Baseline, Week 26 Mean Standing Diastolic Blood Pressure | Baseline | 81.7 mm Hg | Standard Deviation 10.7 |
| Placebo | Baseline, Week 26 Mean Standing Diastolic Blood Pressure | Week 26 | 80.8 mm Hg | Standard Deviation 10 |
Secondary
Baseline, Week 26 Mean Standing Pulse Rate
Time frame: Baseline, Week 26
Population: Treated Set, all patients who were documented to have taken at least one dose of study medication
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pramipexole | Baseline, Week 26 Mean Standing Pulse Rate | Baseline | 74.6 bpm | Standard Deviation 10.2 |
| Pramipexole | Baseline, Week 26 Mean Standing Pulse Rate | Week 26 | 74.1 bpm | Standard Deviation 8.9 |
| Placebo | Baseline, Week 26 Mean Standing Pulse Rate | Baseline | 74.0 bpm | Standard Deviation 10.7 |
| Placebo | Baseline, Week 26 Mean Standing Pulse Rate | Week 26 | 75.0 bpm | Standard Deviation 10.6 |
Secondary
Baseline, Week 26 Mean Standing Systolic Blood Pressure
Time frame: Baseline, Week 26
Population: Treated Set, all patients who were documented to have taken at least one dose of study medication
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pramipexole | Baseline, Week 26 Mean Standing Systolic Blood Pressure | Baseline | 132.6 mm Hg | Standard Deviation 17.3 |
| Pramipexole | Baseline, Week 26 Mean Standing Systolic Blood Pressure | Week 26 | 132.4 mm Hg | Standard Deviation 18.2 |
| Placebo | Baseline, Week 26 Mean Standing Systolic Blood Pressure | Baseline | 130.6 mm Hg | Standard Deviation 18.2 |
| Placebo | Baseline, Week 26 Mean Standing Systolic Blood Pressure | Week 26 | 130.1 mm Hg | Standard Deviation 17.1 |
Secondary
Baseline, Week 26 Mean Supine Diastolic Blood Pressure
Time frame: Baseline, Week 26
Population: Treated Set, all patients who were documented to have taken at least one dose of study medication
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pramipexole | Baseline, Week 26 Mean Supine Diastolic Blood Pressure | Baseline | 79.2 mm Hg | Standard Deviation 9.7 |
| Pramipexole | Baseline, Week 26 Mean Supine Diastolic Blood Pressure | Week 26 | 78.3 mm Hg | Standard Deviation 9.7 |
| Placebo | Baseline, Week 26 Mean Supine Diastolic Blood Pressure | Baseline | 79.6 mm Hg | Standard Deviation 9.7 |
| Placebo | Baseline, Week 26 Mean Supine Diastolic Blood Pressure | Week 26 | 79.5 mm Hg | Standard Deviation 9.4 |
Secondary
Baseline, Week 26 Mean Supine Pulse Rate
Time frame: Baseline, Week 26
Population: Treated Set, all patients who were documented to have taken at least one dose of study medication
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pramipexole | Baseline, Week 26 Mean Supine Pulse Rate | Baseline | 68.5 bpm | Standard Deviation 9.6 |
| Pramipexole | Baseline, Week 26 Mean Supine Pulse Rate | Week 26 | 69.1 bpm | Standard Deviation 8.9 |
| Placebo | Baseline, Week 26 Mean Supine Pulse Rate | Baseline | 68.7 bpm | Standard Deviation 10.6 |
| Placebo | Baseline, Week 26 Mean Supine Pulse Rate | Week 26 | 68.3 bpm | Standard Deviation 10.6 |
Secondary
Baseline, Week 26 Mean Supine Systolic Blood Pressure
Time frame: Baseline, Week 26
Population: Treated Set, all patients who were documented to have taken at least one dose of study medication
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pramipexole | Baseline, Week 26 Mean Supine Systolic Blood Pressure | Baseline | 133.4 mm Hg | Standard Deviation 16.9 |
| Pramipexole | Baseline, Week 26 Mean Supine Systolic Blood Pressure | Week 26 | 132.3 mm Hg | Standard Deviation 16.4 |
| Placebo | Baseline, Week 26 Mean Supine Systolic Blood Pressure | Baseline | 132.7 mm Hg | Standard Deviation 18.4 |
| Placebo | Baseline, Week 26 Mean Supine Systolic Blood Pressure | Week 26 | 132.2 mm Hg | Standard Deviation 16.5 |
Secondary
Change From Baseline in IRLS Mood Disturbance Score (Item 10) After 26 Weeks
Mood disturbance associated with RLS symptoms ranging from 0 (none) to 4 (very severe)
Time frame: Baseline and 26 weeks of treatment
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole | Change From Baseline in IRLS Mood Disturbance Score (Item 10) After 26 Weeks | -1 scores on a scale |
| Placebo | Change From Baseline in IRLS Mood Disturbance Score (Item 10) After 26 Weeks | -1 scores on a scale |
p-value: 0.058395% CI: [0, 0]Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Quality of Life in RLS (RLS QoL) Score After 26 Weeks
RLS QoL total score ranging from 0 to 100 with higher values indicating better quality of life
Time frame: Baseline and 26 weeks of treatment
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole | Change From Baseline in Quality of Life in RLS (RLS QoL) Score After 26 Weeks | 15 Scores on a scale |
| Placebo | Change From Baseline in Quality of Life in RLS (RLS QoL) Score After 26 Weeks | 12.5 Scores on a scale |
p-value: 0.590595% CI: [2.2, 2.8]Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Restless Legs Syndrome-6 (RLS-6) Score Satisfaction With Sleep After 26 Weeks
The score is an 11-point Likert scale, ranging from none/not at all (0) to very severe (10), to reflect the patient's condition during the previous week
Time frame: baseline and 26 weeks of treatment
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole | Change From Baseline in Restless Legs Syndrome-6 (RLS-6) Score Satisfaction With Sleep After 26 Weeks | -2.5 Scores on a scale |
| Placebo | Change From Baseline in Restless Legs Syndrome-6 (RLS-6) Score Satisfaction With Sleep After 26 Weeks | -2 Scores on a scale |
p-value: 0.048995% CI: [-1.1, -0.9]Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in RLS-6 Score Severity During the Day When at Rest After 26 Weeks
The score is an 11-point Likert scale, ranging from none/not at all (0) to very severe (10), to reflect the patient's condition during the previous week
Time frame: Baseline and 26 weeks of treatment
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole | Change From Baseline in RLS-6 Score Severity During the Day When at Rest After 26 Weeks | -3 Scores on a scale |
| Placebo | Change From Baseline in RLS-6 Score Severity During the Day When at Rest After 26 Weeks | -1 Scores on a scale |
p-value: 0.84195% CI: [0, 0]Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in RLS-6 Score Severity During the Night After 26 Weeks
The question was rated on an 11-point Likert scale, ranging from none/not at all (0) to very severe (10), to reflect the patient's condition during the previous week
Time frame: baseline and 26 weeks of treatment
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole | Change From Baseline in RLS-6 Score Severity During the Night After 26 Weeks | -3 Scores on a scale |
| Placebo | Change From Baseline in RLS-6 Score Severity During the Night After 26 Weeks | -2 Scores on a scale |
p-value: 0.073595% CI: [0, 0]Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in RLS-6 Score Severity Falling Asleep After 26 Weeks
The score is an 11-point Likert scale, ranging from none/not at all (0) to very severe (10), to reflect the patient's condition during the previous week
Time frame: Baseline and 26 weeks of treatment
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole | Change From Baseline in RLS-6 Score Severity Falling Asleep After 26 Weeks | -3 Scores on a scale |
| Placebo | Change From Baseline in RLS-6 Score Severity Falling Asleep After 26 Weeks | -1 Scores on a scale |
p-value: 0.031595% CI: [0, 0]Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in RLS-6 Score Tired or Sleepy During the Day After 26 Weeks
The score is an 11-point Likert scale, ranging from none/not at all (0) to very severe (10), to reflect the patient's condition during the previous week
Time frame: Baseline and 26 weeks of treatment
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole | Change From Baseline in RLS-6 Score Tired or Sleepy During the Day After 26 Weeks | -1 Scores on a scale |
| Placebo | Change From Baseline in RLS-6 Score Tired or Sleepy During the Day After 26 Weeks | -1 Scores on a scale |
p-value: 0.809395% CI: [0, 0]Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in SF-36 Dimension General Health After 26 Weeks
Score ranging from 0 to 100 with higher scores indicating better health status
Time frame: Baseline and 26 weeks
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole | Change From Baseline in SF-36 Dimension General Health After 26 Weeks | 0 Scores on a scale |
| Placebo | Change From Baseline in SF-36 Dimension General Health After 26 Weeks | 0 Scores on a scale |
p-value: 0.54595% CI: [1.7, 2.3]Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in SF-36 Dimension Mental Component Summary After 26 Weeks
Score ranging from 0 to 100 with higher scores indicating better health
Time frame: Baseline and 26 weeks
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole | Change From Baseline in SF-36 Dimension Mental Component Summary After 26 Weeks | 1.7 Scores on a scale |
| Placebo | Change From Baseline in SF-36 Dimension Mental Component Summary After 26 Weeks | 1.9 Scores on a scale |
p-value: 0.560295% CI: [0.4, 0.8]Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in SF-36 Dimension Mental Health After 26 Weeks
Score ranging from 0 to 100 with higher scores indicating better mental health
Time frame: Baseline and 26 weeks
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole | Change From Baseline in SF-36 Dimension Mental Health After 26 Weeks | 5 Scores on a scale |
| Placebo | Change From Baseline in SF-36 Dimension Mental Health After 26 Weeks | 5 Scores on a scale |
p-value: 0.145695% CI: [-0.3, 0.3]Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in SF-36 Dimension Physical Component Summary After 26 Weeks
Score ranging from 0 to 100 with higher scores indicating better health
Time frame: Baseline and 26 weeks
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole | Change From Baseline in SF-36 Dimension Physical Component Summary After 26 Weeks | 2.1 Scores on a scale |
| Placebo | Change From Baseline in SF-36 Dimension Physical Component Summary After 26 Weeks | 2 Scores on a scale |
p-value: 0.13695% CI: [0.8, 1.1]Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in SF-36 Dimension Physical Functioning After 26 Weeks
Score ranging from 0 to 100 with higher scores indicating better physical functioning
Time frame: Baseline and 26 weeks
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole | Change From Baseline in SF-36 Dimension Physical Functioning After 26 Weeks | 0 Scores on a scale |
| Placebo | Change From Baseline in SF-36 Dimension Physical Functioning After 26 Weeks | 0 Scores on a scale |
p-value: 0.291595% CI: [-0.4, 0.4]Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in SF-36 Dimension Role Limitations Due to Emotional Problems After 26 Weeks
Score ranging from 0 to 100 with higher scores indicating less limitations due to emotional problems
Time frame: Baseline and 26 weeks
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole | Change From Baseline in SF-36 Dimension Role Limitations Due to Emotional Problems After 26 Weeks | 0 Scores on a scale |
| Placebo | Change From Baseline in SF-36 Dimension Role Limitations Due to Emotional Problems After 26 Weeks | 0 Scores on a scale |
p-value: 0.313195% CI: [-0.4, 0.4]Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in SF-36 Dimension Role Limitations Due to Physical Problems After 26 Weeks
Score ranging from 0 to 100 with higher scores indicating less limitations due to physical problems
Time frame: Baseline and 26 weeks
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole | Change From Baseline in SF-36 Dimension Role Limitations Due to Physical Problems After 26 Weeks | 6.3 Scores on a scale |
| Placebo | Change From Baseline in SF-36 Dimension Role Limitations Due to Physical Problems After 26 Weeks | 6.3 Scores on a scale |
p-value: 0.571395% CI: [-0.4, 0.4]Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in SF-36 Dimension Social Functioning After 26 Weeks
Score ranging from 0 to 100 with higher scores indicating better social functioning
Time frame: Baseline and 26 weeks
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole | Change From Baseline in SF-36 Dimension Social Functioning After 26 Weeks | 0 Scores on a scale |
| Placebo | Change From Baseline in SF-36 Dimension Social Functioning After 26 Weeks | 0 Scores on a scale |
p-value: 0.843295% CI: [-0.4, 0.4]Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in SF-36 Dimension Vitality After 26 Weeks
Score ranging from 0 to 100 with higher scores indicating better vitality
Time frame: Baseline and 26 weeks
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole | Change From Baseline in SF-36 Dimension Vitality After 26 Weeks | 6.3 Scores on a scale |
| Placebo | Change From Baseline in SF-36 Dimension Vitality After 26 Weeks | 3.1 Scores on a scale |
p-value: 0.020695% CI: [5.9, 6.6]Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Short Form-36 (SF-36) Dimension Bodily Pain After 26 Weeks
Score ranging from 0 to 100 with higher scores indicating less bodily pain
Time frame: Baseline and 26 weeks
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole | Change From Baseline in Short Form-36 (SF-36) Dimension Bodily Pain After 26 Weeks | 12 Scores on a scale |
| Placebo | Change From Baseline in Short Form-36 (SF-36) Dimension Bodily Pain After 26 Weeks | 9 Scores on a scale |
p-value: 0.017995% CI: [1.6, 2.4]Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Visual Analogue Scale (VAS) Score for Pain in Limbs After 26 Weeks
The scale measures pain on a continuous 100 mm axis ranging from no pain (0 mm) to unbearable pain (100 mm)
Time frame: Baseline and 26 weeks of treatment
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole | Change From Baseline in Visual Analogue Scale (VAS) Score for Pain in Limbs After 26 Weeks | -26 Scores on a scale |
| Placebo | Change From Baseline in Visual Analogue Scale (VAS) Score for Pain in Limbs After 26 Weeks | -15 Scores on a scale |
p-value: 0.091695% CI: [-5.5, -4.5]Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline RLS-6 Score Severity During the Day Engaged in Activities After 26 Weeks
The score is an 11-point Likert scale, ranging from none/not at all (0) to very severe (10), to reflect the patient's condition during the previous week
Time frame: Baseline and 26 weeks of treatment
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pramipexole | Change From Baseline RLS-6 Score Severity During the Day Engaged in Activities After 26 Weeks | 0 Scores on a scale |
| Placebo | Change From Baseline RLS-6 Score Severity During the Day Engaged in Activities After 26 Weeks | 0 Scores on a scale |
p-value: 0.924195% CI: [0, 0]Wilcoxon (Mann-Whitney)
Secondary
Clinical Global Impression - Global Improvement (CGI-I) Responder Rate
CGI-I scores ranging from '1' (very much improved) to '7' (very much worse), CGI-I responder have scoring 1 or 2 (at least much improved)
Time frame: after 26 weeks of treatment
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pramipexole | Clinical Global Impression - Global Improvement (CGI-I) Responder Rate | CGI-I responder (at least much improved) | 111 participants |
| Pramipexole | Clinical Global Impression - Global Improvement (CGI-I) Responder Rate | CGI-I non-responder | 51 participants |
| Placebo | Clinical Global Impression - Global Improvement (CGI-I) Responder Rate | CGI-I responder (at least much improved) | 80 participants |
| Placebo | Clinical Global Impression - Global Improvement (CGI-I) Responder Rate | CGI-I non-responder | 79 participants |
p-value: 0.001Cochran-Mantel-Haenszel
Secondary
Diagnosis of Classified Augmentation According to Independent Expert Panel
Augmentation is a worsening of RLS symptoms and may manifest as increased severity and the involvement of other extremities or as a shift of RLS symptoms to a time period that is 2 or more hours earlier than was typical of the time of symptom onset during the initial course of beneficial stable treatment or the state before recently starting treatment.
Time frame: after at least 4 weeks of treatment
Population: Treated Set and where patients received study medication for at least 4 weeks (Treated Set includes all patients who were documented to have taken at least one dose of of treatment)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pramipexole | Diagnosis of Classified Augmentation According to Independent Expert Panel | 18 participants |
| Placebo | Diagnosis of Classified Augmentation According to Independent Expert Panel | 14 participants |
Secondary
International Restless Legs Syndrome (IRLS) Study Group Rating Scale Responder Rate
IRLS response was defined as at least 50% reduction in IRLS total score from baseline. IRLS total score ranging from 0 (no RLS symptoms) to 40 (very severe symptoms)
Time frame: after 26 weeks of treatment
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pramipexole | International Restless Legs Syndrome (IRLS) Study Group Rating Scale Responder Rate | IRLS responder | 95 participants |
| Pramipexole | International Restless Legs Syndrome (IRLS) Study Group Rating Scale Responder Rate | IRLS non-responder | 67 participants |
| Placebo | International Restless Legs Syndrome (IRLS) Study Group Rating Scale Responder Rate | IRLS responder | 68 participants |
| Placebo | International Restless Legs Syndrome (IRLS) Study Group Rating Scale Responder Rate | IRLS non-responder | 91 participants |
p-value: 0.0044Cochran-Mantel-Haenszel
Secondary
Patient Global Impression (PGI) Responder Rate
PGI scores ranging from '1' (very much better) to '7' (very much worse), PGI responder have scoring 1 or 2 (at least much better)
Time frame: after 26 weeks of treatment
Population: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pramipexole | Patient Global Impression (PGI) Responder Rate | PGI responder (much better or very much better) | 101 participants |
| Pramipexole | Patient Global Impression (PGI) Responder Rate | PGI non-responder | 61 participants |
| Placebo | Patient Global Impression (PGI) Responder Rate | PGI responder (much better or very much better) | 70 participants |
| Placebo | Patient Global Impression (PGI) Responder Rate | PGI non-responder | 89 participants |
p-value: 0.0011Cochran-Mantel-Haenszel
Secondary
Worsening of RLS Symptoms (by at Least 4 Points in the IRLS Total Score Compared to Baseline) After Treatment Discontinuation
Worsening of RLS symptoms, in comparison to baseline, following abrupt treatment discontinuation (for patients with no added RLS therapy after study drug discontinuation). Assessment of worsening of RLS was based on the IRLS total score assessed 7 ± 1 days after treatment discontinuation (the end of the study or premature discontinuation) compared with that at baseline. Analysis considered the number of patients experiencing a clinically relevant deterioration of ≥4 points in total IRLS score 7 ± 1 days after discontinuation of trial medication compared with baseline.
Time frame: after at least 1 week of treatment discontinuation
Population: Treated Set, all patients who were documented to have taken at least one dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pramipexole | Worsening of RLS Symptoms (by at Least 4 Points in the IRLS Total Score Compared to Baseline) After Treatment Discontinuation | 14 participants |
| Placebo | Worsening of RLS Symptoms (by at Least 4 Points in the IRLS Total Score Compared to Baseline) After Treatment Discontinuation | 2 participants |
p-value: 0.0022Mantel Haenszel