Restless Legs Syndrome
Conditions
Keywords
Moderate, Restless Legs Syndrome, Severe, ropinirole
Brief summary
This is an initial placebo-controlled study followed by open treatment evaluating the effectiveness and tolerability of ropinirole long-term in patients with moderate to severe Restless Legs Syndrome.
Detailed description
A randomised, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of ropinirole for 26 weeks and to further evaluate the incidence of augmentation and rebound for a further 40 weeks open-label extension treatment period in subjects suffering from moderate to severe Restless Legs Syndrome.
Interventions
DRUGPlacebo
Matching Placebo
DRUGRopinirole
Ropinirole IR 0.25mg/day to 4mg/day for RLS
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Male and female subjects, between the ages of 18 and 79, inclusive A female is eligible to enter and participate in the study if she is of: 1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or, 2. Childbearing potential, has a negative result on all required pregnancy tests prior to randomisation, and agrees to an acceptable contraceptive method. * Subjects with a diagnosis of idiopathic RLS using the RLS Diagnostic Clinical Interview and the International RLS Study Group (IRLSSG) Diagnostic Criteria during the Screening Visit. * Subjects have had RLS symptoms with a history of a minimum of 15 RLS episodes during the previous month. If this is not possible due to the subject being on previous medication to treat RLS the investigator should ensure that the subject should have experienced 4-5 episodes of RLS symptoms during the last 7 days of the wash-out phase (see below). The subject must discontinue and wash-out any previous medication for the treatment of RLS or sleep prior to the Baseline Visit (Day 0). The minimum discontinuation period for wash-out is generally 5 half-lives of the medication or 7 consecutive evenings/nights medication-free prior to baseline, whichever is the longer period. * During the Wash-out and Screening Phase, RLS symptoms must be present for at least 4 of the last 7 nights immediately prior to the Baseline Visit (e.g., any combination of evenings and /or nights for = 4 days). * Subjects with a total score = 24 on the IRLS Rating Scale at baseline (Day 0). * Subjects with RLS symptoms that cause significant sleep impairment based on clinical judgment and guided by subject response to Question 4 of the IRLS Rating Scale (e.g., ordinarily this will include a response of (3) severe or (4) very severe sleep disturbance) at the Baseline Visit OR RLS symptoms that cause severe/very severe discomfort in the limbs based on clinical judgment and guided by subject response to Question 1 of the IRLS Rating Scale (e.g., this will include a response of (3) severe or (4) very severe discomfort in limbs) at the Baseline Visit (Day 0). * Subjects must be experiencing RLS symptoms requiring treatment at night-time. * Subjects must have given written informed consent prior to any specific study procedures.
Exclusion criteria
* Subjects suffering from augmentation and/ or 'end of treatment' rebound RLS symptoms at baseline (Day 0). Augmentation is defined as RLS symptoms that occurred while on treatment and occur earlier in the afternoon/evening than they did before, symptoms which are more severe than when not treated, symptoms which start after less time at rest than they did before treatment, or symptoms which involve other parts of the body, such as the arms or trunk. 'End of treatment' rebound describes worsening of symptoms from baseline that occur after pharmacological treatment is stopped. * Subjects with a previous history of augmentation. * Subjects who have exhibited intolerance to ropinirole or any other dopamine agonist. * Subjects requiring treatment of daytime RLS symptoms (daytime defined as 10:00 hours until 17:00 hours). * Signs of secondary RLS (e.g., end stage renal disease, iron deficient anaemia or pregnancy at Baseline Visit). * Subjects with a serum ferritin level of \< 10 mcg/L (ng/mL) at Screening Visit. * Subjects who suffer from a primary sleep disorder other than RLS that may significantly affect the symptoms of RLS (e.g. narcolepsy, sleep terror disorder, sleepwalking disorder, breathing related sleep disorder). * Subjects diagnosed with movement disorders (e.g., Parkinson's Disease, dyskinesias, and dystonias). * Subjects who have medical conditions which could affect efficacy assessments or clinically significant or unstable medical conditions that present a safety concern. These may include, but are not limited to, the following disorders: diabetes, peripheral neuropathy, rheumatoid arthritis, fibromyalgia syndrome, symptomatic orthostatic hypotension, severe cardiovascular disease, hepatic or renal failure, pleuro-pulmonary fibrosis, major psychotic illness. * Subjects having a clinically significant abnormal laboratory value, ECG, or physical examination findings not resolved by the time of the baseline examinations (Day 0). Abnormal 12-lead ECG findings include, but are not limited to, the following: myocardial ischemia, clinically significant conduction abnormalities, or clinically significant arrhythmias. * Subjects with a diastolic blood pressure = 110mmHg or = 50mmHg or systolic blood pressure = 180mmHg or = 90mmHg at the Screening or Baseline Visit. * Subjects with a history of alcohol or substance abuse within the past year. * Subjects taking any medication known to induce drowsiness, affect RLS or sleep and which have not been discontinued prior to the Baseline Visit. These medications include the following: Atypical and typical antipsychotics, anticonvulsants, opioids (including propoxyphene and oxycodone), anxiolytics, all sedatives/hypnotics (including benzodiazepines), lithium, oral neuroleptics, stimulants (including methylphenidate), dopamine agonists (including ropinirole), dopamine antagonists (e.g., typical neuroleptics, metoclopramide), levodopa/carbidopa, clonidine, and sedating antihistamines (e.g., chlorpheniramine, diphenhydramine, hydroxyzine) or any preparations containing these antihistamines. The minimum discontinuation period is generally 5 half lives or 7 consecutive evenings/nights medication free, prior to baseline, whichever is the longer period. Exceptions to this general rule are: fluoxetine, monoamine oxidase inhibitors: 4 weeks. For subjects entering the 40-week, open-label treatment phase, the GSK Medical Monitor can be contacted to discuss individual cases where adherence to the above may not have occurred. * Withdrawal, introduction, or change in dose of hormone replacement therapy (HRT) and/or any drug known to substantially inhibit CYP1A2 (e.g., ciprofloxacin, cimetidine, fluvoxamine, HRT) or induce CYP1A2 (e.g., tobacco, omeprazole) within 7 days prior to enrolment. Subjects already on these agents may be enrolled, but must remain on stable doses of the agents from 7 days prior to enrolment through to the follow-up visit at the end of the study. * Night workers or any others whose sleeping habits are incompatible with the study design, or who would be required to make significant changes to their bedtime during the course of the study. * Participation in any clinical drug or device trial in the one month prior to the Baseline Visit. * Subjects who, in the opinion of the investigator, would be non-compliant with the visit schedules or other study procedures. * Women who have a positive pregnancy test or who are lactating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26 | Baseline and Weeks 12 and 26 | A 10-item, participant-reported scale covering different symptoms of the condition. Each item is scored from 0 to 4; 0 represents the absence of a problem and 4 reflects a very severe problem. The best and worst possible scores are 0 and 40, respectively; higher scores represent a greater severity of symptoms. A negative change from baseline indicates improvement, and a negative treatment difference indicates a benefit of Ropinirole IR over placebo. The primary assessment was made by calculating the difference in the average score obtained at Baseline with scores at Week 12 and then Week 26. |
| Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases | During 15-month study duration at scheduled (Weeks 16, 20, 26, or early withdrawal for DB phase; Weeks 39, 47, 55, 63, 67, or early withdrawal for the OL phase) and unscheduled (26-week DB phase and 40-week OL phase) visits | Clinically meaningful augmentation and early morning rebound (EMR) were assessed and confirmed by an independent Adjudication Board. EMR describes the development of RLS symptoms during the early morning, following therapeutic intervention. EMR is differentiated from augmentation, in which the earlier onset of symptoms occurs in the evening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Sleep Quantity, a Domain of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale, at Weeks 12 and 26 | Baseline and Weeks 12 and 26 | The MOS-12 Sleep Scale is a comprehensive battery, which measures specific aspects of sleep in participants that may have varying co-morbidities, and, as a result, is appropriate for a medically diverse participant population.Scores were adjusted for baseline MOS sleep scale domain value, treatment group, visit, visit by treatment interaction, and center group. |
| Change From Baseline in the Johns Hopkins RLS Quality of Life (RLS QoL) Questionnaire Overall Life Impact Score at Weeks 12 and 26 | Baseline and Weeks 12 and 26 | The Johns Hopkins RLS QoL Questionnaire is a disease-specific instrument that assesses the impact of RLS on the daily life, emotional well-being, social life, and work life of participants. The overall life impact score for the John Hopkins RLS QoL scale ranges from a lowest possible score of 0 to a highest possible score of 100. Higher scores represent better quality of life. Scores were adjusted for baseline RLS Quality of Life score, treatment group, visit, visit by treatment interaction, and center group. |
| Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Baseline and Weeks 12 and 26 | The MOS SF-36 is a generic QoL instrument measuring functional status and well-being. Positive change from baseline for all domains indicates improvement. For all MOS SF-36 domains, the minimum and maximum scores are 0 and 100, respectively, for the transformed scale. Scores were adjusted for baseline domain score, treatment group, visit, visit by treatment interaction, and center group. |
| Percentage of Participants With a Score of Much/Very Much Improved on the Clinical Global Impression-Global Improvement (CGI-I) Scale at Weeks 1, 12 and 26 | Weeks 1, 12 and 26 | The CGI-I is a psychometric instrument that is used to measure general clinical status in a variety of disease states. The CGI-I allows the investigator to rate the participant's global improvement or worsening compared with the condition at Baseline (Day 0). The scale is rated from 1-7 (1 = very much improved; 7 = very much worse). Typically, a participant with a score of 1 or 2 (much improved) is considered a responder. |
| Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at Weeks 1, 4, 8, 16, and 20 | Baseline and Weeks 1, 4, 8, 16, and 20 | A 10-item, participant-reported scale covering different RLS symptoms. Each item is scored from 0 to 4; 0 represents the absence of a problem and 4 reflects a very severe problem. The best and worst possible scores are 0 and 40, respectively; higher scores represent a greater severity of symptoms. The primary assessment from this study was made by calculating the difference in the average score obtained at Baseline with scores at Weeks 1, 4, 8, 16, and 20. Scores were adjusted for baseline IRLS total score, treatment group, visit, visit by treatment group interaction, and center group. |
| Number of Participants Rated as Normal or Borderline Ill on the CGI Severity of Illness (CGI-S) Scale at Week 26 | Week 26 | The CGI-S scale is a psychometric instrument that is used to measure general clinical status in a variety of disease states. The CGI-S allows the investigator to rate the severity of the participant's illness considering their total clinical experience with the subject population being studied and on all information available at the time of rating. The scale is rated from 1-7 (1 = normal, not at all ill; 2 = borderline ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severly ill; 7 = among the most extremely ill participants). |
| Median Time to First CGI-I Response of Much/Very Much Improved During the Double-blind Phase | Baseline to Week 26 | The median time to first CGI-I response of much/very much improved was calculated. The CGI-I is a psychometric instrument that is used to measure general clinical status in a variety of disease states. The CGI-I allows the investigator to rate the participant's global improvement or worsening compared with the condition at Baseline (Day 0). The scale is rated from 1-7 (1 = very much improved; 7 = very much worse). Typically, a participant with a score of 1 or 2 (much improved) is considered a responder. |
| Number of Participants With a Score of Much/Very Much Improved on the CGI-I Scale at Week 67 | Week 67 | The CGI-I is a psychometric instrument that is used to measure general clinical status in a variety of disease states. The CGI-I allows the investigator to rate the participant's global improvement or worsening compared with the condition at Baseline (Day 0). The scale is rated from 1-7 (1 = very much improved; 7 = very much worse). Typically, a participant with a score of 1 or 2 (much improved) is considered a responder. |
| Mean Change From Baseline in the IRLS Rating Scale Total Score at Week 67 | Baseline and Week 67 | A 10-item, participant-reported scale covering different symptoms of the condition. Each item is scored from 0 to 4, with 0 representing the absence of a problem and 4 reflecting a very severe problem. The best and worst possible scores are 0 and 40, respectively. The primary assessment was made by calculating the difference in the average score obtained at Baseline with score at Week 67. |
| Number of Participants Withdrawing Due to Lack of Efficacy During the First 26 Weeks of the Study | Baseline to Week 26 | Lack of efficacy is defined as up to a 10% improvement in the IRLS Rating Scale total score from the participant's Baseline value and at least 12 weeks of treatment during the double-blind phase. |
| Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26 | Baseline and Weeks 12 and 26 | The MOS-12 Sleep Scale is a comprehensive battery, which measures specific aspects of sleep in participants that may have varying co-morbidities, and, as a result, is appropriate for a medically diverse participant population. Domain values are presented on a 0-100 scale, where a higher score means a greater degree of the attribute implied by the scale name. Scores were adjusted for baseline MOS sleep scale domain value, treatment group, visit, visit by treatment interaction, and center group. |
Countries
Australia, Czechia, Denmark, Germany, Italy, Norway, Portugal, Slovakia, Spain, Sweden, Switzerland
Participant flow
Recruitment details
Participants (par.) could enter the Open-Label (OL) phase at the end of the Double-Blind (DB) phase. If a par. did not complete the DB phase due to lack of efficacy, he/she could also be considered for entry into the OL phase if the investigator considered it appropriate and the par. met the protocol-defined criteria in describing lack of efficacy.
Participants by arm
| Arm | Count |
|---|---|
| Double-Blind Placebo Matching placebo tablets | 207 |
| Double-Blind Ropinirole IR Ropinirole IR (immediate release) tablets containing ropinirole hydrochloride equivalent to 0.25 mg, 0.5 mg, 1.0 mg, or 2.0 mg of the active drug substance, taken once a day | 197 |
| Total | 404 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| 26-Week Double-Blind Treatment Phase | Did not complete phase; reason unknown | 119 | 99 | 0 |
| 40-Week Open-Label Treatment Phase | Adverse Event | 0 | 0 | 20 |
| 40-Week Open-Label Treatment Phase | Captured as Other | 0 | 0 | 4 |
| 40-Week Open-Label Treatment Phase | Lack of Efficacy | 0 | 0 | 9 |
| 40-Week Open-Label Treatment Phase | Lost to Follow-up | 0 | 0 | 1 |
| 40-Week Open-Label Treatment Phase | Protocol Violation | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Double-Blind Ropinirole IR | Total | Double-Blind Placebo |
|---|---|---|---|
| Age, Continuous | 56.5 years STANDARD_DEVIATION 11.97 | 56.2 years STANDARD_DEVIATION 11.73 | 55.9 years STANDARD_DEVIATION 11.53 |
| Race/Ethnicity, Customized Asian | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized Hawaiian or other Pacific Islander | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 197 participants | 401 participants | 204 participants |
| Sex: Female, Male Female | 124 Participants | 256 Participants | 132 Participants |
| Sex: Female, Male Male | 73 Participants | 148 Participants | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 71 / 207 | 123 / 197 | 122 / 269 |
| serious Total, serious adverse events | 6 / 207 | 6 / 197 | 11 / 269 |
Outcome results
Primary
Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26
A 10-item, participant-reported scale covering different symptoms of the condition. Each item is scored from 0 to 4; 0 represents the absence of a problem and 4 reflects a very severe problem. The best and worst possible scores are 0 and 40, respectively; higher scores represent a greater severity of symptoms. A negative change from baseline indicates improvement, and a negative treatment difference indicates a benefit of Ropinirole IR over placebo. The primary assessment was made by calculating the difference in the average score obtained at Baseline with scores at Week 12 and then Week 26.
Time frame: Baseline and Weeks 12 and 26
Population: Intention-to-Treat (ITT) Population: all randomised participants who received at least one dose of study medication, and for whom at least one valid post-baseline efficacy assessment was available. Analysis is based on the observed cases for each visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind Placebo | Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26 | Week 12, n=165, 164 | -12.1 points on a scale | Standard Error 0.7 |
| Double-blind Placebo | Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26 | Week 26, n=119, 123 | -13.4 points on a scale | Standard Error 0.77 |
| Double-blind Ropinirole IR | Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26 | Week 12, n=165, 164 | -14.2 points on a scale | Standard Error 0.71 |
| Double-blind Ropinirole IR | Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26 | Week 26, n=119, 123 | -15.9 points on a scale | Standard Error 0.76 |
p-value: 0.039Repeated Measures Mixed Model
p-value: 0.023Repeated Measures Mixed Model
Primary
Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases
Clinically meaningful augmentation and early morning rebound (EMR) were assessed and confirmed by an independent Adjudication Board. EMR describes the development of RLS symptoms during the early morning, following therapeutic intervention. EMR is differentiated from augmentation, in which the earlier onset of symptoms occurs in the evening.
Time frame: During 15-month study duration at scheduled (Weeks 16, 20, 26, or early withdrawal for DB phase; Weeks 39, 47, 55, 63, 67, or early withdrawal for the OL phase) and unscheduled (26-week DB phase and 40-week OL phase) visits
Population: Safety Population: all participants who received at least one dose of study medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-blind Placebo | Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases | Confirmed augmentation | 15 participants |
| Double-blind Placebo | Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases | Confirmed EMR | 7 participants |
| Double-blind Placebo | Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases | Clinically meaningful augmentation | 11 participants |
| Double-blind Ropinirole IR | Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases | Confirmed augmentation | 1 participants |
| Double-blind Ropinirole IR | Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases | Confirmed EMR | 1 participants |
| Double-blind Ropinirole IR | Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases | Clinically meaningful augmentation | 1 participants |
| Double-blind Ropinirole IR | Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases | Clinically meaningful augmentation | 5 participants |
| Double-blind Ropinirole IR | Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases | Confirmed augmentation | 7 participants |
| Double-blind Ropinirole IR | Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases | Confirmed EMR | 4 participants |
| Open-label Ropinirole IR | Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases | Confirmed augmentation | 8 participants |
| Open-label Ropinirole IR | Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases | Confirmed EMR | 2 participants |
| Open-label Ropinirole IR | Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases | Clinically meaningful augmentation | 5 participants |
Secondary
Change From Baseline in Sleep Quantity, a Domain of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale, at Weeks 12 and 26
The MOS-12 Sleep Scale is a comprehensive battery, which measures specific aspects of sleep in participants that may have varying co-morbidities, and, as a result, is appropriate for a medically diverse participant population.Scores were adjusted for baseline MOS sleep scale domain value, treatment group, visit, visit by treatment interaction, and center group.
Time frame: Baseline and Weeks 12 and 26
Population: Intention-to-Treat (ITT) Population: all randomised participants who received at least one dose of study medication, and for whom at least one valid post-baseline efficacy assessment was available. Analysis is based on the observed cases for each visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind Placebo | Change From Baseline in Sleep Quantity, a Domain of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale, at Weeks 12 and 26 | Week 12, n=153, 143 | 0.5 hours | Standard Error 0.1 |
| Double-blind Placebo | Change From Baseline in Sleep Quantity, a Domain of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale, at Weeks 12 and 26 | Week 26, n=105, 97 | 0.5 hours | Standard Error 0.11 |
| Double-blind Ropinirole IR | Change From Baseline in Sleep Quantity, a Domain of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale, at Weeks 12 and 26 | Week 12, n=153, 143 | 0.7 hours | Standard Error 0.11 |
| Double-blind Ropinirole IR | Change From Baseline in Sleep Quantity, a Domain of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale, at Weeks 12 and 26 | Week 26, n=105, 97 | 0.7 hours | Standard Error 0.11 |
Secondary
Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26
The MOS-12 Sleep Scale is a comprehensive battery, which measures specific aspects of sleep in participants that may have varying co-morbidities, and, as a result, is appropriate for a medically diverse participant population. Domain values are presented on a 0-100 scale, where a higher score means a greater degree of the attribute implied by the scale name. Scores were adjusted for baseline MOS sleep scale domain value, treatment group, visit, visit by treatment interaction, and center group.
Time frame: Baseline and Weeks 12 and 26
Population: Intention-to-Treat (ITT) Population: all randomised participants who received at least one dose of study medication, and for whom at least one valid post-baseline efficacy assessment was available. Analysis is based on the observed cases for each visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind Placebo | Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26 | Sleep disturbance, Week 12, n=153, 143 | -15.0 points on a scale | Standard Error 1.62 |
| Double-blind Placebo | Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26 | Sleep disturbance, Week 26, n=105, 97 | -16.4 points on a scale | Standard Error 1.8 |
| Double-blind Placebo | Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26 | Sleep adequacy, Week 12, n=153, 143 | 15.0 points on a scale | Standard Error 1.91 |
| Double-blind Placebo | Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26 | Sleep adequacy, Week 26, n=105, 97 | 14.9 points on a scale | Standard Error 2.16 |
| Double-blind Placebo | Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26 | Daytime somnolence, Week 12, n=153, 143 | -7.5 points on a scale | Standard Error 1.28 |
| Double-blind Placebo | Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26 | Daytime somnolence, Week 26, n=105, 97 | -9.1 points on a scale | Standard Error 1.59 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26 | Daytime somnolence, Week 12, n=153, 143 | -11.4 points on a scale | Standard Error 1.33 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26 | Sleep disturbance, Week 12, n=153, 143 | -24.0 points on a scale | Standard Error 1.67 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26 | Sleep adequacy, Week 26, n=105, 97 | 26.0 points on a scale | Standard Error 2.25 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26 | Sleep disturbance, Week 26, n=105, 97 | -24.6 points on a scale | Standard Error 1.87 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26 | Daytime somnolence, Week 26, n=105, 97 | -11.4 points on a scale | Standard Error 1.65 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26 | Sleep adequacy, Week 12, n=153, 143 | 22.8 points on a scale | Standard Error 1.98 |
Secondary
Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26
The MOS SF-36 is a generic QoL instrument measuring functional status and well-being. Positive change from baseline for all domains indicates improvement. For all MOS SF-36 domains, the minimum and maximum scores are 0 and 100, respectively, for the transformed scale. Scores were adjusted for baseline domain score, treatment group, visit, visit by treatment interaction, and center group.
Time frame: Baseline and Weeks 12 and 26
Population: Intention-to-Treat (ITT) Population: all randomised participants who received at least one dose of study medication, and for whom at least one valid post-baseline efficacy assessment was available. Analysis is based on the observed cases for each visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind Placebo | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Bodily pain, Week 12, n=149, 142 | 12.3 points on a scale | Standard Error 1.72 |
| Double-blind Placebo | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Bodily pain, Week 26, n=104, 94 | 13.3 points on a scale | Standard Error 2.01 |
| Double-blind Placebo | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | General health, Week 12, n=149, 142 | 3.0 points on a scale | Standard Error 1.08 |
| Double-blind Placebo | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | General health, Week 26, n=104, 94 | 2.6 points on a scale | Standard Error 1.31 |
| Double-blind Placebo | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Mental health, Week 12, n=149, 142 | 5.0 points on a scale | Standard Error 1.22 |
| Double-blind Placebo | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Mental health, Week 26, n=104, 94 | 4.6 points on a scale | Standard Error 1.25 |
| Double-blind Placebo | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Physical functioning, Week 12, n=149, 142 | 2.4 points on a scale | Standard Error 1.22 |
| Double-blind Placebo | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Physical functioning, Week 26, n=104, 94 | 3.5 points on a scale | Standard Error 1.48 |
| Double-blind Placebo | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Role emotional, Week 12, n=149, 142 | 5.1 points on a scale | Standard Error 1.62 |
| Double-blind Placebo | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Role emotional, Week 26, n=104, 94 | 5.9 points on a scale | Standard Error 1.66 |
| Double-blind Placebo | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Role physical, Week 12, n=149, 142 | 5.2 points on a scale | Standard Error 1.66 |
| Double-blind Placebo | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Role physical, Week 26, n=104, 94 | 7.5 points on a scale | Standard Error 1.85 |
| Double-blind Placebo | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Social functioning, Week 12, n=149, 142 | 6.3 points on a scale | Standard Error 1.58 |
| Double-blind Placebo | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Social functioning, Week 26, n=104, 94 | 7.1 points on a scale | Standard Error 1.56 |
| Double-blind Placebo | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Vitality, Week 12, n=149, 142 | 8.0 points on a scale | Standard Error 1.37 |
| Double-blind Placebo | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Vitality, Week 26, n=104, 94 | 6.0 points on a scale | Standard Error 1.54 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Vitality, Week 26, n=104, 94 | 9.2 points on a scale | Standard Error 1.61 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Bodily pain, Week 12, n=149, 142 | 14.4 points on a scale | Standard Error 1.76 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Role emotional, Week 12, n=149, 142 | 7.0 points on a scale | Standard Error 1.67 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Bodily pain, Week 26, n=104, 94 | 14.0 points on a scale | Standard Error 2.11 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Social functioning, Week 12, n=149, 142 | 9.8 points on a scale | Standard Error 1.62 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | General health, Week 12, n=149, 142 | 4.5 points on a scale | Standard Error 1.11 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Role emotional, Week 26, n=104, 94 | 6.6 points on a scale | Standard Error 1.74 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | General health, Week 26, n=104, 94 | 4.1 points on a scale | Standard Error 1.37 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Vitality, Week 12, n=149, 142 | 9.3 points on a scale | Standard Error 1.41 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Mental health, Week 12, n=149, 142 | 7.6 points on a scale | Standard Error 1.26 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Role physical, Week 12, n=149, 142 | 7.7 points on a scale | Standard Error 1.71 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Mental health, Week 26, n=104, 94 | 6.2 points on a scale | Standard Error 1.31 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Social functioning, Week 26, n=104, 94 | 8.8 points on a scale | Standard Error 1.63 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Physical functioning, Week 12, n=149, 142 | 5.5 points on a scale | Standard Error 1.25 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Role physical, Week 26, n=104, 94 | 6.7 points on a scale | Standard Error 1.94 |
| Double-blind Ropinirole IR | Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26 | Physical functioning, Week 26, n=104, 94 | 2.6 points on a scale | Standard Error 1.54 |
Secondary
Change From Baseline in the Johns Hopkins RLS Quality of Life (RLS QoL) Questionnaire Overall Life Impact Score at Weeks 12 and 26
The Johns Hopkins RLS QoL Questionnaire is a disease-specific instrument that assesses the impact of RLS on the daily life, emotional well-being, social life, and work life of participants. The overall life impact score for the John Hopkins RLS QoL scale ranges from a lowest possible score of 0 to a highest possible score of 100. Higher scores represent better quality of life. Scores were adjusted for baseline RLS Quality of Life score, treatment group, visit, visit by treatment interaction, and center group.
Time frame: Baseline and Weeks 12 and 26
Population: Intention-to-Treat (ITT) Population: all randomised participants who received at least one dose of study medication, and for whom at least one valid post-baseline efficacy assessment was available. Analysis is based on the observed cases for each visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind Placebo | Change From Baseline in the Johns Hopkins RLS Quality of Life (RLS QoL) Questionnaire Overall Life Impact Score at Weeks 12 and 26 | Week 12, n=149, 141 | 14.0 points on a scale | Standard Error 1.29 |
| Double-blind Placebo | Change From Baseline in the Johns Hopkins RLS Quality of Life (RLS QoL) Questionnaire Overall Life Impact Score at Weeks 12 and 26 | Week 26, n=103, 94 | 16.5 points on a scale | Standard Error 1.35 |
| Double-blind Ropinirole IR | Change From Baseline in the Johns Hopkins RLS Quality of Life (RLS QoL) Questionnaire Overall Life Impact Score at Weeks 12 and 26 | Week 12, n=149, 141 | 18.0 points on a scale | Standard Error 1.33 |
| Double-blind Ropinirole IR | Change From Baseline in the Johns Hopkins RLS Quality of Life (RLS QoL) Questionnaire Overall Life Impact Score at Weeks 12 and 26 | Week 26, n=103, 94 | 18.5 points on a scale | Standard Error 1.41 |
Secondary
Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at Weeks 1, 4, 8, 16, and 20
A 10-item, participant-reported scale covering different RLS symptoms. Each item is scored from 0 to 4; 0 represents the absence of a problem and 4 reflects a very severe problem. The best and worst possible scores are 0 and 40, respectively; higher scores represent a greater severity of symptoms. The primary assessment from this study was made by calculating the difference in the average score obtained at Baseline with scores at Weeks 1, 4, 8, 16, and 20. Scores were adjusted for baseline IRLS total score, treatment group, visit, visit by treatment group interaction, and center group.
Time frame: Baseline and Weeks 1, 4, 8, 16, and 20
Population: Intention-to-Treat (ITT) Population: all randomised participants who received at least one dose of study medication, and for whom at least one valid post-baseline efficacy assessment was available. Analysis is based on the observed cases for each visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind Placebo | Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at Weeks 1, 4, 8, 16, and 20 | Week 4, n=183, 180 | -10.5 points on a scale | Standard Error 0.6 |
| Double-blind Placebo | Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at Weeks 1, 4, 8, 16, and 20 | Week 16, n=137, 144 | -12.6 points on a scale | Standard Error 0.75 |
| Double-blind Placebo | Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at Weeks 1, 4, 8, 16, and 20 | Week 8, n=168, 170 | -13.0 points on a scale | Standard Error 0.66 |
| Double-blind Placebo | Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at Weeks 1, 4, 8, 16, and 20 | Week 20, n=125, 132 | -12.3 points on a scale | Standard Error 0.78 |
| Double-blind Placebo | Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at Weeks 1, 4, 8, 16, and 20 | Week 1, n=198, 194 | -5.5 points on a scale | Standard Error 0.52 |
| Double-blind Ropinirole IR | Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at Weeks 1, 4, 8, 16, and 20 | Week 20, n=125, 132 | -15.7 points on a scale | Standard Error 0.77 |
| Double-blind Ropinirole IR | Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at Weeks 1, 4, 8, 16, and 20 | Week 1, n=198, 194 | -7.8 points on a scale | Standard Error 0.52 |
| Double-blind Ropinirole IR | Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at Weeks 1, 4, 8, 16, and 20 | Week 4, n=183, 180 | -13.6 points on a scale | Standard Error 0.6 |
| Double-blind Ropinirole IR | Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at Weeks 1, 4, 8, 16, and 20 | Week 8, n=168, 170 | -15.3 points on a scale | Standard Error 0.66 |
| Double-blind Ropinirole IR | Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at Weeks 1, 4, 8, 16, and 20 | Week 16, n=137, 144 | -15.0 points on a scale | Standard Error 0.74 |
Secondary
Mean Change From Baseline in the IRLS Rating Scale Total Score at Week 67
A 10-item, participant-reported scale covering different symptoms of the condition. Each item is scored from 0 to 4, with 0 representing the absence of a problem and 4 reflecting a very severe problem. The best and worst possible scores are 0 and 40, respectively. The primary assessment was made by calculating the difference in the average score obtained at Baseline with score at Week 67.
Time frame: Baseline and Week 67
Population: Open-Label ITT Population: all participants who were enrolled into the Open-Label Phase of the study, received at least one dose of Open-Label study medication, and had a baseline IRLS total score and on-treatment IRLS assessment. Analysis is based on the observed cases for each visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Double-blind Placebo | Mean Change From Baseline in the IRLS Rating Scale Total Score at Week 67 | -20.4 points on a scale | Standard Deviation 8.36 |
Secondary
Median Time to First CGI-I Response of Much/Very Much Improved During the Double-blind Phase
The median time to first CGI-I response of much/very much improved was calculated. The CGI-I is a psychometric instrument that is used to measure general clinical status in a variety of disease states. The CGI-I allows the investigator to rate the participant's global improvement or worsening compared with the condition at Baseline (Day 0). The scale is rated from 1-7 (1 = very much improved; 7 = very much worse). Typically, a participant with a score of 1 or 2 (much improved) is considered a responder.
Time frame: Baseline to Week 26
Population: Intention-to-Treat (ITT) Population: all randomised participants who received at least one dose of study medication, and for whom at least one valid post-baseline efficacy assessment was available
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Double-blind Placebo | Median Time to First CGI-I Response of Much/Very Much Improved During the Double-blind Phase | 28 days |
| Double-blind Ropinirole IR | Median Time to First CGI-I Response of Much/Very Much Improved During the Double-blind Phase | 21 days |
Secondary
Number of Participants Rated as Normal or Borderline Ill on the CGI Severity of Illness (CGI-S) Scale at Week 26
The CGI-S scale is a psychometric instrument that is used to measure general clinical status in a variety of disease states. The CGI-S allows the investigator to rate the severity of the participant's illness considering their total clinical experience with the subject population being studied and on all information available at the time of rating. The scale is rated from 1-7 (1 = normal, not at all ill; 2 = borderline ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severly ill; 7 = among the most extremely ill participants).
Time frame: Week 26
Population: Intention-to-Treat (ITT) Population: all randomised participants who received at least one dose of study medication, and for whom at least one valid post-baseline efficacy assessment was available. Data are presented for the participants still in the study and assessed at Week 26, which is less than those randomised at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind Placebo | Number of Participants Rated as Normal or Borderline Ill on the CGI Severity of Illness (CGI-S) Scale at Week 26 | 50 participants |
| Double-blind Ropinirole IR | Number of Participants Rated as Normal or Borderline Ill on the CGI Severity of Illness (CGI-S) Scale at Week 26 | 50 participants |
Secondary
Number of Participants With a Score of Much/Very Much Improved on the CGI-I Scale at Week 67
The CGI-I is a psychometric instrument that is used to measure general clinical status in a variety of disease states. The CGI-I allows the investigator to rate the participant's global improvement or worsening compared with the condition at Baseline (Day 0). The scale is rated from 1-7 (1 = very much improved; 7 = very much worse). Typically, a participant with a score of 1 or 2 (much improved) is considered a responder.
Time frame: Week 67
Population: Open-Label (OL) ITT Population: all participants who were enrolled into the OL Phase of the study, received at least one dose of OL study medication, and had a baseline IRLS total score and on-treatment IRLS assessment. Data are presented for participants still in the study and assessed at Week 26, which is less than those randomized at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind Placebo | Number of Participants With a Score of Much/Very Much Improved on the CGI-I Scale at Week 67 | 184 participants |
Secondary
Number of Participants Withdrawing Due to Lack of Efficacy During the First 26 Weeks of the Study
Lack of efficacy is defined as up to a 10% improvement in the IRLS Rating Scale total score from the participant's Baseline value and at least 12 weeks of treatment during the double-blind phase.
Time frame: Baseline to Week 26
Population: Intention-to-Treat (ITT) Population: all randomised participants who received at least one dose of study medication, and for whom at least one valid post-baseline efficacy assessment was available
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind Placebo | Number of Participants Withdrawing Due to Lack of Efficacy During the First 26 Weeks of the Study | 2 participants |
| Double-blind Ropinirole IR | Number of Participants Withdrawing Due to Lack of Efficacy During the First 26 Weeks of the Study | 3 participants |
Secondary
Percentage of Participants With a Score of Much/Very Much Improved on the Clinical Global Impression-Global Improvement (CGI-I) Scale at Weeks 1, 12 and 26
The CGI-I is a psychometric instrument that is used to measure general clinical status in a variety of disease states. The CGI-I allows the investigator to rate the participant's global improvement or worsening compared with the condition at Baseline (Day 0). The scale is rated from 1-7 (1 = very much improved; 7 = very much worse). Typically, a participant with a score of 1 or 2 (much improved) is considered a responder.
Time frame: Weeks 1, 12 and 26
Population: Intention-to-Treat (ITT) Population. Analysis is based on the observed cases for each visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-blind Placebo | Percentage of Participants With a Score of Much/Very Much Improved on the Clinical Global Impression-Global Improvement (CGI-I) Scale at Weeks 1, 12 and 26 | Week 1, n=192, 192 | 39 percentage of participants |
| Double-blind Placebo | Percentage of Participants With a Score of Much/Very Much Improved on the Clinical Global Impression-Global Improvement (CGI-I) Scale at Weeks 1, 12 and 26 | Week 12, n=165, 160 | 86 percentage of participants |
| Double-blind Placebo | Percentage of Participants With a Score of Much/Very Much Improved on the Clinical Global Impression-Global Improvement (CGI-I) Scale at Weeks 1, 12 and 26 | Week 26, n=112, 108 | 72 percentage of participants |
| Double-blind Ropinirole IR | Percentage of Participants With a Score of Much/Very Much Improved on the Clinical Global Impression-Global Improvement (CGI-I) Scale at Weeks 1, 12 and 26 | Week 1, n=192, 192 | 50 percentage of participants |
| Double-blind Ropinirole IR | Percentage of Participants With a Score of Much/Very Much Improved on the Clinical Global Impression-Global Improvement (CGI-I) Scale at Weeks 1, 12 and 26 | Week 12, n=165, 160 | 109 percentage of participants |
| Double-blind Ropinirole IR | Percentage of Participants With a Score of Much/Very Much Improved on the Clinical Global Impression-Global Improvement (CGI-I) Scale at Weeks 1, 12 and 26 | Week 26, n=112, 108 | 91 percentage of participants |
Post Hoc
Post-hoc Analysis of Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26, Exploring the Impact of Center Group on Treatment Effect
A post-hoc analysis of the primary outcome measure, exploring the variation in treatment effects across center groups by excluding those with the most extreme treatment effects, was conducted. Centers were grouped into five center groups.
Time frame: Baseline and Weeks 12 and 26
Population: ITT Population excluding the two center groups with the most extreme treatment effects. Analysis is based on the observed cases for each visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Double-blind Placebo | Post-hoc Analysis of Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26, Exploring the Impact of Center Group on Treatment Effect | Week 12, n=136, 134 | -12.2 Points on a scale | Standard Error 0.78 |
| Double-blind Placebo | Post-hoc Analysis of Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26, Exploring the Impact of Center Group on Treatment Effect | Week 26, n=103, 105 | -14.0 Points on a scale | Standard Error 0.84 |
| Double-blind Ropinirole IR | Post-hoc Analysis of Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26, Exploring the Impact of Center Group on Treatment Effect | Week 12, n=136, 134 | -13.8 Points on a scale | Standard Error 0.79 |
| Double-blind Ropinirole IR | Post-hoc Analysis of Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26, Exploring the Impact of Center Group on Treatment Effect | Week 26, n=103, 105 | -15.7 Points on a scale | Standard Error 0.83 |
Post Hoc
Post-hoc Analysis of Percentage of Participants With a Score of Much/Very Much Improved on the Clinical Global Impression-Global Improvement (CGI-I) Scale at Weeks 12 and 26, Exploring the Impact of Center Group on Treatment Effect
A post-hoc analysis of CGI-I, exploring the variation in treatment effects across center groups by excluding the same two center groups as in the IRLS post-hoc analysis, was conducted. Centers were grouped into five center groups.
Time frame: Weeks 12 and 26
Population: ITT Population excluding the same two center groups as in the IRLS post-hoc analysis. Analysis is based on the observed cases for each visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-blind Placebo | Post-hoc Analysis of Percentage of Participants With a Score of Much/Very Much Improved on the Clinical Global Impression-Global Improvement (CGI-I) Scale at Weeks 12 and 26, Exploring the Impact of Center Group on Treatment Effect | Week 12, n=136, 134 | 75 Number of responders |
| Double-blind Placebo | Post-hoc Analysis of Percentage of Participants With a Score of Much/Very Much Improved on the Clinical Global Impression-Global Improvement (CGI-I) Scale at Weeks 12 and 26, Exploring the Impact of Center Group on Treatment Effect | Week 26, n=99, 96 | 63 Number of responders |
| Double-blind Ropinirole IR | Post-hoc Analysis of Percentage of Participants With a Score of Much/Very Much Improved on the Clinical Global Impression-Global Improvement (CGI-I) Scale at Weeks 12 and 26, Exploring the Impact of Center Group on Treatment Effect | Week 12, n=136, 134 | 93 Number of responders |
| Double-blind Ropinirole IR | Post-hoc Analysis of Percentage of Participants With a Score of Much/Very Much Improved on the Clinical Global Impression-Global Improvement (CGI-I) Scale at Weeks 12 and 26, Exploring the Impact of Center Group on Treatment Effect | Week 26, n=99, 96 | 82 Number of responders |