Idiopathic Restless Legs Syndrome
Conditions
Keywords
RLS
Brief summary
This purpose of this study is to investigate the efficacy and tolerability of pregabalin in treating idiopathic RLS patients for up to 12 months.
Interventions
DRUGplacebo and pregabalin
following 3 months placebo treatment, subjects are to be re-distributed to pregabalin 300 mg per day for 9 months. Both placebo and pregabalin are to be administered orally once a day, 1-3 hours before bedtime.
DRUGpramipexol
following 3 months placebo treatment, subjects are to be re-distributed to pramipexol 0.25mg per day for 9 months. Both placebo and pramipexol are to be administered orally once a day, 1-3 hours before bedtime.
DRUGPregabalin
pregabalin 300 mg, orally administered once a day, 1- 3 hours before the bedtime for 12 months
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* idiopathic RLS with the presence of all four clinical manifestations of RLS * RLS symptoms occur predominantly in the evening * RLS history at least 6 months * IRLS =\> 15 at the beginning and the end of placebo run-in * Have =\>15 nights with RLS symptoms in the month prior to screening
Exclusion criteria
* Any secondary RLS * Current augmentation due to RLS treatment * Placebo responders identified during the placebo run-in
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Restless Legs Syndrome (RLS) Symptom Severity | Baseline | International Restless Legs Syndrome Study Group Rating Scale (IRLS) is psychometrically and clinically valid and reliable clinician-administered instrument used to assess the severity of RLS. It assesses RLS symptom severity and impact on daily living and is comprised of 10 items, scored on 0 to 4 scale, where lower score indicates lower symptom severity/impact on living. Two subscale scores are symptom severity (6 items) ranging from 0-24 (lower score indicates lower symptom severity) and impact on daily living (3 items) ranging from 0-12 (lower score indicates lower impact on living). Item 3 is unrelated to the other items. The global score is calculated from all 10 items, range from 0 to 40, where lower scores reflect lower severity and better quality of life. |
| Change From Baseline in the RLS Symptom Severity at Week 12 | Baseline, Week 12 | IRLS is psychometrically and clinically valid and reliable clinician-administered instrument used to assess the severity of RLS. It assesses RLS symptom severity and impact on daily living and is comprised of 10 items, scored on 0 to 4 scale, where lower score indicates lower symptom severity/impact on living. Two subscale scores are symptom severity (6 items) ranging from 0-24 (lower score indicates lower symptom severity) and impact on daily living (3 items) ranging from 0-12 (lower score indicates lower impact on living). Item 3 is unrelated to the other items. The global score is calculated from all 10 items, range from 0 to 40, where lower scores reflect lower severity and better quality of life. |
| Percentage of Participants Responding to Treatment at Week 12 | Week 12 | CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. Responders were defined as participants who report CGI-I score of very much improved or much improved. |
| Percentage of Participants With Augmentation | Baseline up to Week 52 | Augmentation was worsening of RLS symptoms, attributable to a specific long-term therapeutic intervention for RLS. Percentage of participants with augmentation was evaluated by centralized evaluation board using a set of assessment criteria for potential augmentation which included structured interview for diagnosis of augmentation during RLS treatment (SIDA-RLS), augmentation severity rating scale (ASRS), clinical judgment. ASRS measures severity of augmentation and consist of three items to be completed by clinician. Clinician would score participants' answers by comparing post-baseline evaluations to those at baseline. ASRS total score range: 0-24, with higher score indicating more severe augmentation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subjective Sleep Questionnaire (SSQ): Number of Awakenings Subscale Score at Week 12 | Week 12 | SSQ: Participant-rated instrument used to assess previous night's sleep profile. It is used to measure sleep quantity and quality and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), total WASO (1 item), quality of sleep (1 item). Number of awakenings subscale: numerical rating completed by the participant 30 minutes after waking; recall period is the night before. Number of awakenings subscale score ranges from 0-30. Lower value indicates better sleep. |
| Subjective Sleep Questionnaire (SSQ): Quality of Sleep Subscale Score at Week 12 | Week 12 | SSQ: Participant-rated instrument used to assess previous night's sleep profile. It is used to measure sleep quantity and quality and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), total WASO (1 item), quality of sleep (1 item). Quality of sleep subscale: numerical rating completed by the participant 30 minutes after waking; recall period is the night before. Quality of sleep subscale score ranges from 0-100. Higher score indicates better quality of sleep. |
| RLS-Next Day Impact (RLS-NDI) | Baseline | The RLS-NDI is a participant-rated instrument designed to assess daytime performance as related to RLS and the participant's previous night's sleep. The instrument consists of 14 items that encompass 5 domains: tiredness; emotional functioning; social functioning; cognitive functioning; and activities of daily living. There is also 1 global item assessing overall well -being. Each item is scored on a 0-10 numeric rating scale. Total score is the sum of scores from question 1 to 14. The total score ranges from 0 to 140 where higher scores indicate a more severe impact. |
| Change From Baseline in RLS-NDI at Week 12 | Baseline, Week 12 | The RLS-NDI is a participant-rated instrument designed to assess daytime performance as related to RLS and the participant's previous night's sleep. The instrument consists of 14 items that encompass 5 domains: tiredness; emotional functioning; social functioning; cognitive functioning; and activities of daily living. There is also 1 global item assessing overall well -being. Each item is scored on a 0-10 numeric rating scale. Total score is the sum of scores from question 1 to 14. The total score ranges from 0 to 140 where higher scores indicate a more severe impact. |
| Limb Pain-Visual Analog Scale (Limb Pain-VAS) | Baseline | 100 millimeter (mm) line (Visual Analog Scale) marked by participant. Intensity of pain range (over past week): 0 mm = no pain to 100 mm = worst possible pain. |
| Change From Baseline in Limb Pain-VAS at Week 12 | Baseline, Week 12 | 100 mm line (VAS) marked by participant. Intensity of pain range (over past week): 0 mm = no pain to 100 mm = worst possible pain. Change = observation mean minus baseline mean. |
| Severity of Augmentation Symptoms at Week 12 | Week 12 | ASRS measures severity of augmentation and consist of three items to be completed by clinician. Clinician would score participants' answers by comparing post-baseline evaluations to those at baseline. ASRS total score range: 0-24, with higher score indicating more severe augmentation. |
| Subjective Sleep Questionnaire (SSQ): Subjective Waking After Sleep Onset (WASO) | Baseline | SSQ: Participant-rated instrument used to assess previous night's sleep profile. It is used to measure sleep quantity and quality and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), total WASO (1 item), quality of sleep (1 item). WASO is time spent awake from sleep onset to final awakening. Total WASO subscale (in minutes): numerical rating completed by the participant 30 minutes after waking; recall period is the night before. Total WASO subscale score ranges from 0-1440 minutes. Lower value indicates better sleep. |
| Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Week 12 | MOS-SS: Participant rated instrument to assess sleep quantity, quality; comprised of 12 items yielding 7 subscale scores: sleep disturbance, snoring, awakening short of breath/headache, sleep adequacy, somnolence, sleep quantity, optimal sleep, 2 composite index scores: sleep problems Index I, II. Sleep adequacy data was reported at week 12 and not for first 12 weeks (average). Subscale scores range: 0-100; exception quantity of sleep (range 0-24 hours). With exception of sleep quantity and sleep adequacy, higher scores reflect poorer sleep outcomes. |
| Number of Participants With Medical Outcomes Study-Sleep Scale (MOS-SS)- Optimal Sleep at Week 12 | Week 12 | MOS-SS: Participant rated instrument to assess sleep quantity, quality; comprised of 12 items yielding 7 subscale scores: sleep disturbance, snoring, awakening short of breath/ headache, sleep adequacy, somnolence, sleep quantity, optimal sleep, 2 composite index scores: sleep problems Index I, II. Optimal sleep subscale scores range: 0-1; Optimal sleep = 1 if 'Average hours sleep' = 7 or 8, is 0 if 'Average hours sleep' is non-missing and less than 7, and is missing if 'Average hours sleep' is missing. Higher scores reflect better sleep outcomes. |
| Profile of Mood State (POMS) at Week 12 | Week 12 | POMS are participant-rated instrument comprising 6 sub-scales (tension-anxiety, depression-dejection, anger-hostility, vigor-activity, fatigue-inertia, and confusion-bewilderment) and each subscale comprising 5 items, on 'How you feel right now?' (Scale: 0=not at all, 1=a little, 2=moderately, 3=quite a bit, 4=extremely). All items were rated in the same direction except for vigor-activity. A total score is obtained for each scale. The range of total score is 0 - 100, with higher score indicating more mood disturbance. |
| Restless Legs Syndrome-Quality of Life Scale (RLS-QoL) at Week 12 | Week 12 | RLS QoL: Participant rated instrument used to assess the impact of RLS on quality of life and health status function (symptom severity, daily activity, social functioning, sleep, concentrating and decision making, traveling, sexual activity, and work) yielding a summary score ranging from 0-100. Higher scores reflect better quality of life. |
| Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Week 12 | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being (physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health); 2 summary scores (physical and mental component); and self evaluated change in health status (summary of health status). The score for subscale scores and 2 summary score is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Summary of health status is a 5-point Likert scale ranging from 0=much worse now to 4=much better now. Higher subscale and summary score reflect better health status. |
| Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) at Week 12 | Week 12 | WPAI: 6 question participant rated questionnaire to determine degree to which SHP affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 10 (completely affected/impaired). WPAI outcomes expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. |
| Clinical Global Impressions-Severity (CGI-S) at Week 12 | Week 12 | CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal-not ill at all) to 7 (among the most extremely ill participants). Higher score = more affected. |
| Change From Baseline in SSQ: Subjective WASO at Week 12 | Baseline, Week 12 | SSQ: Participant-rated instrument used to assess previous night's sleep profile. It is used to measure sleep quantity and quality and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), total WASO (1 item), quality of sleep (1 item). WASO is time spent awake from sleep onset to final awakening. Total WASO subscale (in minutes): numerical rating completed by the participant 30 minutes after waking; recall period is the night before. Total WASO subscale score ranges from 0-1440 minutes. Lower value indicates better sleep. |
| Subjective Sleep Questionnaire (SSQ): Latency Subscale Score at Week 12 | Week 12 | SSQ: Participant-rated instrument used to assess previous night's sleep profile. It is used to measure sleep quantity and quality and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), total WASO (1 item), quality of sleep (1 item). Latency subscale (in minutes): numerical rating completed by the participant 30 minutes after waking; recall period is the night before. Latency subscale score ranges from 0-840 minutes. Lower value indicates better sleep. |
| Subjective Sleep Questionnaire (SSQ): Hours of Sleep Subscale Score at Week 12 | Week 12 | SSQ: Participant-rated instrument used to assess previous night's sleep profile. It is used to measure sleep quantity and quality and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), total WASO (1 item), quality of sleep (1 item). Hours of sleep subscale: numerical rating completed by the participant 30 minutes after waking; recall period is the night before. Hours of sleep subscale score ranges from 0-16 hours. Higher value indicates better sleep. |
Countries
Austria, Finland, Germany, Italy, Netherlands, Spain, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pregabalin 300 mg Pregabalin (PGB) capsule 300 milligram (mg) once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 52 weeks along with placebo (PBO) capsule matched to PGB 300 mg in week 13 and 14. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment. | 182 |
| Pramipexole 0.25 mg Pramipexole (PPX) 0.25 mg capsules administered once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6 onwards: 0.25 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.25 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment. | 178 |
| Pramipexole 0.5 mg PPX capsule 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 52 weeks along with PBO capsule matched to PPX 0.5 mg in week 13 and 14. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment. | 180 |
| Placebo to Pregabalin 300 mg PBO capsules matched to PGB 300 mg once daily following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) for 12 weeks, re-randomized to PGB 300 mg following a two week up escalation (Day 1-5: 75 mg once daily; Day 6-10: 150 mg once daily and Day 11 onwards: 300 mg once daily) up to 40 weeks. Participants were administered a tapering dose of PGB 150 mg once daily (Day 1-3); 75 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment. | 59 |
| Placebo to Pramipexole 0.25 mg PBO capsules matched to PPX 0.25 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily and Day 6 onwards: 0.25 mg once daily) for 12 weeks, re-randomized to PPX 0.25 mg following a two week up escalation (Day 1-5: 0.125 mg once daily and Day 6 onwards: 0.25 mg once daily) up to 40 weeks. Participants were administered a tapering dose of PPX 0.125 mg once daily (Day 1-3) and matching PBO capsule once daily (Day 4-7) after completion of 52 weeks treatment. | 59 |
| Placebo to Pramipexole 0.5 mg PBO capsules matched to PPX 0.5 mg once daily following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) for 12 weeks, re-randomized to PPX 0.5 mg following a two week up escalation (Day 1-5: 0.125 mg once daily; Day 6-10: 0.25 mg once daily and Day 11 onwards: 0.5 mg once daily) up to 40 weeks. Participants were administered a tapering dose of PPX 0.25 mg once daily (Day 1-3); 0.125 mg once daily (Day 4-6) and matching PBO capsule once daily on Day 7 after completion of 52 weeks treatment. | 61 |
| Total | 719 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 52 | 35 | 44 | 17 | 9 | 9 |
| Overall Study | Death | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Did not meet entrance criteria | 4 | 1 | 2 | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 5 | 18 | 13 | 4 | 8 | 7 |
| Overall Study | Lost to Follow-up | 8 | 15 | 8 | 2 | 6 | 6 |
| Overall Study | Other | 3 | 6 | 8 | 2 | 0 | 4 |
| Overall Study | Protocol Violation | 6 | 9 | 9 | 0 | 2 | 3 |
| Overall Study | Withdrawal by Subject | 14 | 17 | 9 | 2 | 5 | 3 |
Baseline characteristics
| Characteristic | Pregabalin 300 mg | Total | Placebo to Pramipexole 0.5 mg | Placebo to Pramipexole 0.25 mg | Placebo to Pregabalin 300 mg | Pramipexole 0.5 mg | Pramipexole 0.25 mg |
|---|---|---|---|---|---|---|---|
| Age, Customized 18 to 44 years | 37 Participants | 164 Participants | 20 Participants | 17 Participants | 11 Participants | 45 Participants | 34 Participants |
| Age, Customized 45 to 64 years | 101 Participants | 362 Participants | 31 Participants | 32 Participants | 29 Participants | 84 Participants | 85 Participants |
| Age, Customized Greater than and equal to 65 years | 44 Participants | 193 Participants | 10 Participants | 10 Participants | 19 Participants | 51 Participants | 59 Participants |
| Age, Customized Less than 18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 123 Participants | 441 Participants | 38 Participants | 36 Participants | 37 Participants | 99 Participants | 108 Participants |
| Sex: Female, Male Male | 59 Participants | 278 Participants | 23 Participants | 23 Participants | 22 Participants | 81 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 134 / 182 | 110 / 178 | 118 / 180 | 42 / 59 | 34 / 59 | 41 / 61 |
| serious Total, serious adverse events | 9 / 182 | 12 / 178 | 9 / 180 | 5 / 59 | 2 / 59 | 0 / 61 |
Outcome results
Primary
Change From Baseline in the RLS Symptom Severity at Week 12
IRLS is psychometrically and clinically valid and reliable clinician-administered instrument used to assess the severity of RLS. It assesses RLS symptom severity and impact on daily living and is comprised of 10 items, scored on 0 to 4 scale, where lower score indicates lower symptom severity/impact on living. Two subscale scores are symptom severity (6 items) ranging from 0-24 (lower score indicates lower symptom severity) and impact on daily living (3 items) ranging from 0-12 (lower score indicates lower impact on living). Item 3 is unrelated to the other items. The global score is calculated from all 10 items, range from 0 to 40, where lower scores reflect lower severity and better quality of life.
Time frame: Baseline, Week 12
Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin 300 mg | Change From Baseline in the RLS Symptom Severity at Week 12 | -11.80 Units on a Scale | Standard Error 0.47 |
| Pramipexole 0.25 mg | Change From Baseline in the RLS Symptom Severity at Week 12 | -7.90 Units on a Scale | Standard Error 0.49 |
| Pramipexole 0.5 mg | Change From Baseline in the RLS Symptom Severity at Week 12 | -10.50 Units on a Scale | Standard Error 0.47 |
| Placebo | Change From Baseline in the RLS Symptom Severity at Week 12 | -7.30 Units on a Scale | Standard Error 0.48 |
Comparison: For pregabalin 300 mg versus placebo: Mixed model analysis was used to analyze RLS symptom severity score with baseline value, region \[United states (US) or European union (EU)\], treatment, week and treatment by week interaction as fixed effects.p-value: <0.000195% CI: [-5.9, -3.2]Mixed Models Analysis
Comparison: For pramipexole 0.25 mg versus placebo: Mixed model analysis was used to analyze RLS symptom severity score with baseline value, region (US or EU), treatment, week and treatment by week interaction as fixed effects.p-value: 0.360395% CI: [-2, 0.7]Mixed Models Analysis
Comparison: For pramipexole 0.5 mg versus placebo: Mixed model analysis was used to analyze RLS symptom severity score with baseline value, region (US or EU), treatment, week and treatment by week interaction as fixed effects.p-value: <0.000195% CI: [-4.5, -1.9]Mixed Models Analysis
Primary
Percentage of Participants Responding to Treatment at Week 12
CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. Responders were defined as participants who report CGI-I score of very much improved or much improved.
Time frame: Week 12
Population: ITT population. Last observation carried forward (LOCF) method was used. Here, 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin 300 mg | Percentage of Participants Responding to Treatment at Week 12 | 71.40 Percentage of participants |
| Pramipexole 0.25 mg | Percentage of Participants Responding to Treatment at Week 12 | 51.20 Percentage of participants |
| Pramipexole 0.5 mg | Percentage of Participants Responding to Treatment at Week 12 | 62.70 Percentage of participants |
| Placebo | Percentage of Participants Responding to Treatment at Week 12 | 46.80 Percentage of participants |
Comparison: For pregabalin 300 mg versus placebo: Cochran-Mantel-Haenszel (CMH) test stratified by geographical region (US or EU) was used to analyze CGI-I responder status.p-value: <0.0001Cochran-Mantel-Haenszel
Comparison: For pramipexole 0.25 mg versus placebo: CMH test stratified by geographical region (US or EU) was used to analyze CGI-I responder status.p-value: 0.4393Cochran-Mantel-Haenszel
Comparison: For pramipexole 0.5 mg versus placebo: CMH test stratified by geographical region (US or EU) was used to analyze CGI-I responder status.p-value: 0.0022Cochran-Mantel-Haenszel
Primary
Percentage of Participants With Augmentation
Augmentation was worsening of RLS symptoms, attributable to a specific long-term therapeutic intervention for RLS. Percentage of participants with augmentation was evaluated by centralized evaluation board using a set of assessment criteria for potential augmentation which included structured interview for diagnosis of augmentation during RLS treatment (SIDA-RLS), augmentation severity rating scale (ASRS), clinical judgment. ASRS measures severity of augmentation and consist of three items to be completed by clinician. Clinician would score participants' answers by comparing post-baseline evaluations to those at baseline. ASRS total score range: 0-24, with higher score indicating more severe augmentation.
Time frame: Baseline up to Week 52
Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin 300 mg | Percentage of Participants With Augmentation | 1.70 Percentage of participants |
| Pramipexole 0.25 mg | Percentage of Participants With Augmentation | 6.60 Percentage of participants |
| Pramipexole 0.5 mg | Percentage of Participants With Augmentation | 9.00 Percentage of participants |
Comparison: For pramipexole 0.25 mg versus pregabalin 300 mg: Stratified log rank test by block (40 weeks versus 52 weeks of active treatment) was used to calculate p-value.p-value: 0.0826Log Rank
Comparison: For pramipexole 0.5 mg versus pregabalin 300 mg: Stratified log rank test by block (40 weeks versus 52 weeks of active treatment) was used to calculate p-value.p-value: 0.0012Log Rank
Primary
Restless Legs Syndrome (RLS) Symptom Severity
International Restless Legs Syndrome Study Group Rating Scale (IRLS) is psychometrically and clinically valid and reliable clinician-administered instrument used to assess the severity of RLS. It assesses RLS symptom severity and impact on daily living and is comprised of 10 items, scored on 0 to 4 scale, where lower score indicates lower symptom severity/impact on living. Two subscale scores are symptom severity (6 items) ranging from 0-24 (lower score indicates lower symptom severity) and impact on daily living (3 items) ranging from 0-12 (lower score indicates lower impact on living). Item 3 is unrelated to the other items. The global score is calculated from all 10 items, range from 0 to 40, where lower scores reflect lower severity and better quality of life.
Time frame: Baseline
Population: Intent-to-treat (ITT) population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin 300 mg | Restless Legs Syndrome (RLS) Symptom Severity | 22.30 Units on a Scale | Standard Deviation 5.73 |
| Pramipexole 0.25 mg | Restless Legs Syndrome (RLS) Symptom Severity | 22.40 Units on a Scale | Standard Deviation 5.37 |
| Pramipexole 0.5 mg | Restless Legs Syndrome (RLS) Symptom Severity | 22.10 Units on a Scale | Standard Deviation 5.19 |
| Placebo | Restless Legs Syndrome (RLS) Symptom Severity | 22.40 Units on a Scale | Standard Deviation 5.58 |
Secondary
Change From Baseline in Limb Pain-VAS at Week 12
100 mm line (VAS) marked by participant. Intensity of pain range (over past week): 0 mm = no pain to 100 mm = worst possible pain. Change = observation mean minus baseline mean.
Time frame: Baseline, Week 12
Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin 300 mg | Change From Baseline in Limb Pain-VAS at Week 12 | -3.20 mm | Standard Error 0.2 |
| Pramipexole 0.25 mg | Change From Baseline in Limb Pain-VAS at Week 12 | -2.64 mm | Standard Error 0.2 |
| Pramipexole 0.5 mg | Change From Baseline in Limb Pain-VAS at Week 12 | -2.75 mm | Standard Error 0.21 |
| Placebo | Change From Baseline in Limb Pain-VAS at Week 12 | -2.20 mm | Standard Error 0.2 |
Comparison: For pregabalin 300 mg versus placebo: Mixed model analysis was used to analyze limb pain-VAS with baseline value, region (US or EU), treatment, week and treatment by week interaction as fixed effects.p-value: 0.000495% CI: [-1.55, -0.45]Mixed Models Analysis
Comparison: For pramipexole 0.25 mg versus placebo: Mixed model analysis was used to analyze limb pain-VAS with baseline value, region (US or EU), treatment, week and treatment by week interaction as fixed effects.p-value: 0.124295% CI: [-0.99, 0.12]Mixed Models Analysis
Comparison: For pramipexole 0.5 mg versus placebo: Mixed model analysis was used to analyze limb pain-VAS with baseline value, region (US or EU), treatment, week and treatment by week interaction as fixed effects.p-value: 0.055395% CI: [-1.12, 0.01]Mixed Models Analysis
Secondary
Change From Baseline in RLS-NDI at Week 12
The RLS-NDI is a participant-rated instrument designed to assess daytime performance as related to RLS and the participant's previous night's sleep. The instrument consists of 14 items that encompass 5 domains: tiredness; emotional functioning; social functioning; cognitive functioning; and activities of daily living. There is also 1 global item assessing overall well -being. Each item is scored on a 0-10 numeric rating scale. Total score is the sum of scores from question 1 to 14. The total score ranges from 0 to 140 where higher scores indicate a more severe impact.
Time frame: Baseline, Week 12
Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin 300 mg | Change From Baseline in RLS-NDI at Week 12 | -8.10 Units on a Scale | Standard Error 2.88 |
| Pramipexole 0.25 mg | Change From Baseline in RLS-NDI at Week 12 | -4.30 Units on a Scale | Standard Error 2.65 |
| Pramipexole 0.5 mg | Change From Baseline in RLS-NDI at Week 12 | -14.50 Units on a Scale | Standard Error 2.5 |
| Placebo | Change From Baseline in RLS-NDI at Week 12 | -6.60 Units on a Scale | Standard Error 2.68 |
Comparison: For pregabalin 300 mg versus placebo: Mixed model analysis was used to analyze RLS-NDI with baseline value, region (US or EU), treatment, week and treatment by week interaction as fixed effects.p-value: 0.707395% CI: [-9.3, 6.3]Mixed Models Analysis
Comparison: For pramipexole 0.25 mg versus placebo: Mixed model analysis was used to analyze RLS-NDI with baseline value, region (US or EU), treatment, week and treatment by week interaction as fixed effects.p-value: 0.529995% CI: [-5.1, 9.9]Mixed Models Analysis
Comparison: For pramipexole 0.5 mg versus placebo: Mixed model analysis was used to analyze RLS-NDI with baseline value, region (US or EU), treatment, week and treatment by week interaction as fixed effects.p-value: 0.035495% CI: [-15.2, -0.5]Mixed Models Analysis
Secondary
Change From Baseline in SSQ: Subjective WASO at Week 12
SSQ: Participant-rated instrument used to assess previous night's sleep profile. It is used to measure sleep quantity and quality and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), total WASO (1 item), quality of sleep (1 item). WASO is time spent awake from sleep onset to final awakening. Total WASO subscale (in minutes): numerical rating completed by the participant 30 minutes after waking; recall period is the night before. Total WASO subscale score ranges from 0-1440 minutes. Lower value indicates better sleep.
Time frame: Baseline, Week 12
Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin 300 mg | Change From Baseline in SSQ: Subjective WASO at Week 12 | -49.86 minutes | Standard Error 3.06 |
| Pramipexole 0.25 mg | Change From Baseline in SSQ: Subjective WASO at Week 12 | -33.69 minutes | Standard Error 3.15 |
| Pramipexole 0.5 mg | Change From Baseline in SSQ: Subjective WASO at Week 12 | -37.18 minutes | Standard Error 3.04 |
| Placebo | Change From Baseline in SSQ: Subjective WASO at Week 12 | -32.61 minutes | Standard Error 3.1 |
Comparison: For pregabalin 300 mg versus placebo: Mixed model analysis was used to analyze SSQ-Subjective WASO score with baseline value, region (US or EU), treatment, week and treatment by week interaction as fixed effects.p-value: <0.000195% CI: [-25.76, -8.74]Mixed Models Analysis
Comparison: For pramipexole 0.25 mg versus placebo: Mixed model analysis was used to analyze SSQ-Subjective WASO score with baseline value, region (US or EU), treatment, week and treatment by week interaction as fixed effects.p-value: 0.807595% CI: [-9.73, 7.58]Mixed Models Analysis
Comparison: For pramipexole 0.5 mg versus placebo: Mixed model analysis was used to analyze SSQ-Subjective WASO score with baseline value, region (US or EU), treatment, week and treatment by week interaction as fixed effects.p-value: 0.290695% CI: [-13.05, 3.91]Mixed Models Analysis
Secondary
Clinical Global Impressions-Severity (CGI-S) at Week 12
CGI-S: 7-point clinician rated scale to assess severity of participant's current illness state; range: 1 (normal-not ill at all) to 7 (among the most extremely ill participants). Higher score = more affected.
Time frame: Week 12
Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin 300 mg | Clinical Global Impressions-Severity (CGI-S) at Week 12 | 2.90 Units on a Scale | Standard Deviation 1.18 |
| Pramipexole 0.25 mg | Clinical Global Impressions-Severity (CGI-S) at Week 12 | 3.50 Units on a Scale | Standard Deviation 1.22 |
| Pramipexole 0.5 mg | Clinical Global Impressions-Severity (CGI-S) at Week 12 | 3.10 Units on a Scale | Standard Deviation 1.17 |
| Placebo | Clinical Global Impressions-Severity (CGI-S) at Week 12 | 3.70 Units on a Scale | Standard Deviation 1.17 |
Secondary
Limb Pain-Visual Analog Scale (Limb Pain-VAS)
100 millimeter (mm) line (Visual Analog Scale) marked by participant. Intensity of pain range (over past week): 0 mm = no pain to 100 mm = worst possible pain.
Time frame: Baseline
Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin 300 mg | Limb Pain-Visual Analog Scale (Limb Pain-VAS) | 4.20 mm | Standard Deviation 2.7 |
| Pramipexole 0.25 mg | Limb Pain-Visual Analog Scale (Limb Pain-VAS) | 4.30 mm | Standard Deviation 2.58 |
| Pramipexole 0.5 mg | Limb Pain-Visual Analog Scale (Limb Pain-VAS) | 4.00 mm | Standard Deviation 2.53 |
| Placebo | Limb Pain-Visual Analog Scale (Limb Pain-VAS) | 4.10 mm | Standard Deviation 2.52 |
Secondary
Medical Outcomes Study-Short Form 36 (SF-36) at Week 12
SF-36 is a standardized survey evaluating 8 aspects of functional health and well being (physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health); 2 summary scores (physical and mental component); and self evaluated change in health status (summary of health status). The score for subscale scores and 2 summary score is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Summary of health status is a 5-point Likert scale ranging from 0=much worse now to 4=much better now. Higher subscale and summary score reflect better health status.
Time frame: Week 12
Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin 300 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Physical functioning | 83.70 Units on a Scale | Standard Deviation 18.3 |
| Pregabalin 300 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Social functioning | 87.20 Units on a Scale | Standard Deviation 18.01 |
| Pregabalin 300 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Role emotional | 85.10 Units on a Scale | Standard Deviation 18.91 |
| Pregabalin 300 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Mental health | 77.40 Units on a Scale | Standard Deviation 16.13 |
| Pregabalin 300 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Summary of health status | 3.10 Units on a Scale | Standard Deviation 0.47 |
| Pregabalin 300 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Role physical | 81.20 Units on a Scale | Standard Deviation 20.75 |
| Pregabalin 300 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Bodily pain | 73.30 Units on a Scale | Standard Deviation 20.51 |
| Pregabalin 300 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Summary mental score | 78.00 Units on a Scale | Standard Deviation 15.73 |
| Pregabalin 300 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | General health | 73.60 Units on a Scale | Standard Deviation 18.37 |
| Pregabalin 300 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Summary physical score | 78.00 Units on a Scale | Standard Deviation 16.5 |
| Pregabalin 300 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Vitality | 62.40 Units on a Scale | Standard Deviation 19.27 |
| Pramipexole 0.25 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Summary physical score | 74.20 Units on a Scale | Standard Deviation 15.92 |
| Pramipexole 0.25 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Role emotional | 83.90 Units on a Scale | Standard Deviation 17.77 |
| Pramipexole 0.25 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Role physical | 79.60 Units on a Scale | Standard Deviation 19.37 |
| Pramipexole 0.25 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Social functioning | 84.50 Units on a Scale | Standard Deviation 18.14 |
| Pramipexole 0.25 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Summary mental score | 75.50 Units on a Scale | Standard Deviation 15.6 |
| Pramipexole 0.25 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Vitality | 59.00 Units on a Scale | Standard Deviation 19.69 |
| Pramipexole 0.25 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Bodily pain | 65.20 Units on a Scale | Standard Deviation 20.14 |
| Pramipexole 0.25 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Mental health | 74.60 Units on a Scale | Standard Deviation 16.8 |
| Pramipexole 0.25 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | General health | 69.80 Units on a Scale | Standard Deviation 18.33 |
| Pramipexole 0.25 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Summary of health status | 3.10 Units on a Scale | Standard Deviation 0.49 |
| Pramipexole 0.25 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Physical functioning | 81.90 Units on a Scale | Standard Deviation 19.56 |
| Pramipexole 0.5 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Vitality | 59.80 Units on a Scale | Standard Deviation 20.17 |
| Pramipexole 0.5 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Physical functioning | 82.40 Units on a Scale | Standard Deviation 19.98 |
| Pramipexole 0.5 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | General health | 70.50 Units on a Scale | Standard Deviation 17.68 |
| Pramipexole 0.5 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Role physical | 79.10 Units on a Scale | Standard Deviation 20.71 |
| Pramipexole 0.5 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Bodily pain | 69.00 Units on a Scale | Standard Deviation 20.4 |
| Pramipexole 0.5 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Social functioning | 84.00 Units on a Scale | Standard Deviation 18.75 |
| Pramipexole 0.5 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Role emotional | 84.60 Units on a Scale | Standard Deviation 18.09 |
| Pramipexole 0.5 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Mental health | 76.10 Units on a Scale | Standard Deviation 16.29 |
| Pramipexole 0.5 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Summary physical score | 75.30 Units on a Scale | Standard Deviation 16.43 |
| Pramipexole 0.5 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Summary mental score | 76.10 Units on a Scale | Standard Deviation 15.32 |
| Pramipexole 0.5 mg | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Summary of health status | 3.20 Units on a Scale | Standard Deviation 0.54 |
| Placebo | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Mental health | 78.70 Units on a Scale | Standard Deviation 15.23 |
| Placebo | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | General health | 72.80 Units on a Scale | Standard Deviation 19.47 |
| Placebo | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Bodily pain | 65.50 Units on a Scale | Standard Deviation 20.03 |
| Placebo | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Summary mental score | 78.00 Units on a Scale | Standard Deviation 15.76 |
| Placebo | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Summary physical score | 75.70 Units on a Scale | Standard Deviation 16.03 |
| Placebo | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Role physical | 81.50 Units on a Scale | Standard Deviation 19.7 |
| Placebo | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Social functioning | 86.80 Units on a Scale | Standard Deviation 18.37 |
| Placebo | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Vitality | 59.30 Units on a Scale | Standard Deviation 20.51 |
| Placebo | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Physical functioning | 83.00 Units on a Scale | Standard Deviation 19.22 |
| Placebo | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Role emotional | 87.00 Units on a Scale | Standard Deviation 18.25 |
| Placebo | Medical Outcomes Study-Short Form 36 (SF-36) at Week 12 | Summary of health status | 3.10 Units on a Scale | Standard Deviation 0.53 |
Secondary
Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12
MOS-SS: Participant rated instrument to assess sleep quantity, quality; comprised of 12 items yielding 7 subscale scores: sleep disturbance, snoring, awakening short of breath/headache, sleep adequacy, somnolence, sleep quantity, optimal sleep, 2 composite index scores: sleep problems Index I, II. Sleep adequacy data was reported at week 12 and not for first 12 weeks (average). Subscale scores range: 0-100; exception quantity of sleep (range 0-24 hours). With exception of sleep quantity and sleep adequacy, higher scores reflect poorer sleep outcomes.
Time frame: Week 12
Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, 'n' is signifying those participants who were evaluable for particular category for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin 300 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Sleep disturbance (n = 175, 169, 178, 171) | 30.50 Units on a Scale | Standard Deviation 21.84 |
| Pregabalin 300 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Awakening short of breath (n = 175, 169, 178, 171) | 10.50 Units on a Scale | Standard Deviation 15.78 |
| Pregabalin 300 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Snoring (n = 172, 169, 178, 170) | 29.00 Units on a Scale | Standard Deviation 27.5 |
| Pregabalin 300 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Sleep quantity (n = 175, 169, 178, 171) | 6.80 Units on a Scale | Standard Deviation 1.08 |
| Pregabalin 300 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Sleep problem index I (n = 175, 169, 178, 171) | 29.40 Units on a Scale | Standard Deviation 17.26 |
| Pregabalin 300 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Sleep adequacy (n = 128, 120, 133, 125 ) | 61.30 Units on a Scale | Standard Deviation 28.57 |
| Pregabalin 300 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Sleep problem index II (n = 175, 169, 178, 171) | 30.70 Units on a Scale | Standard Deviation 17.15 |
| Pregabalin 300 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Somnolence (n = 175, 169, 178, 171) | 23.90 Units on a Scale | Standard Deviation 17.57 |
| Pramipexole 0.25 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Snoring (n = 172, 169, 178, 170) | 25.80 Units on a Scale | Standard Deviation 28.46 |
| Pramipexole 0.25 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Sleep quantity (n = 175, 169, 178, 171) | 6.50 Units on a Scale | Standard Deviation 1.25 |
| Pramipexole 0.25 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Sleep problem index II (n = 175, 169, 178, 171) | 36.60 Units on a Scale | Standard Deviation 18.9 |
| Pramipexole 0.25 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Sleep disturbance (n = 175, 169, 178, 171) | 39.30 Units on a Scale | Standard Deviation 23.72 |
| Pramipexole 0.25 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Awakening short of breath (n = 175, 169, 178, 171) | 12.30 Units on a Scale | Standard Deviation 17.09 |
| Pramipexole 0.25 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Somnolence (n = 175, 169, 178, 171) | 27.60 Units on a Scale | Standard Deviation 18.61 |
| Pramipexole 0.25 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Sleep adequacy (n = 128, 120, 133, 125 ) | 54.80 Units on a Scale | Standard Deviation 29.45 |
| Pramipexole 0.25 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Sleep problem index I (n = 175, 169, 178, 171) | 35.30 Units on a Scale | Standard Deviation 18.82 |
| Pramipexole 0.5 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Sleep quantity (n = 175, 169, 178, 171) | 6.60 Units on a Scale | Standard Deviation 1.16 |
| Pramipexole 0.5 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Sleep problem index II (n = 175, 169, 178, 171) | 34.10 Units on a Scale | Standard Deviation 17.05 |
| Pramipexole 0.5 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Somnolence (n = 175, 169, 178, 171) | 25.50 Units on a Scale | Standard Deviation 18.67 |
| Pramipexole 0.5 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Sleep adequacy (n = 128, 120, 133, 125 ) | 55.20 Units on a Scale | Standard Deviation 27.87 |
| Pramipexole 0.5 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Snoring (n = 172, 169, 178, 170) | 25.80 Units on a Scale | Standard Deviation 25.81 |
| Pramipexole 0.5 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Sleep disturbance (n = 175, 169, 178, 171) | 34.40 Units on a Scale | Standard Deviation 20.89 |
| Pramipexole 0.5 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Sleep problem index I (n = 175, 169, 178, 171) | 33.40 Units on a Scale | Standard Deviation 16.73 |
| Pramipexole 0.5 mg | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Awakening short of breath (n = 175, 169, 178, 171) | 13.80 Units on a Scale | Standard Deviation 18.22 |
| Placebo | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Sleep problem index II (n = 175, 169, 178, 171) | 36.30 Units on a Scale | Standard Deviation 16.81 |
| Placebo | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Sleep disturbance (n = 175, 169, 178, 171) | 38.60 Units on a Scale | Standard Deviation 21.43 |
| Placebo | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Snoring (n = 172, 169, 178, 170) | 24.60 Units on a Scale | Standard Deviation 24.57 |
| Placebo | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Awakening short of breath (n = 175, 169, 178, 171) | 9.60 Units on a Scale | Standard Deviation 15.13 |
| Placebo | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Sleep adequacy (n = 128, 120, 133, 125 ) | 50.00 Units on a Scale | Standard Deviation 28.74 |
| Placebo | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Somnolence (n = 175, 169, 178, 171) | 26.00 Units on a Scale | Standard Deviation 18.77 |
| Placebo | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Sleep quantity (n = 175, 169, 178, 171) | 6.50 Units on a Scale | Standard Deviation 1.26 |
| Placebo | Medical Outcomes Study-Sleep Scale (MOS-SS) at Week 12 | Sleep problem index I (n = 175, 169, 178, 171) | 35.00 Units on a Scale | Standard Deviation 16.54 |
Secondary
Number of Participants With Medical Outcomes Study-Sleep Scale (MOS-SS)- Optimal Sleep at Week 12
MOS-SS: Participant rated instrument to assess sleep quantity, quality; comprised of 12 items yielding 7 subscale scores: sleep disturbance, snoring, awakening short of breath/ headache, sleep adequacy, somnolence, sleep quantity, optimal sleep, 2 composite index scores: sleep problems Index I, II. Optimal sleep subscale scores range: 0-1; Optimal sleep = 1 if 'Average hours sleep' = 7 or 8, is 0 if 'Average hours sleep' is non-missing and less than 7, and is missing if 'Average hours sleep' is missing. Higher scores reflect better sleep outcomes.
Time frame: Week 12
Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin 300 mg | Number of Participants With Medical Outcomes Study-Sleep Scale (MOS-SS)- Optimal Sleep at Week 12 | 84 Participants |
| Pramipexole 0.25 mg | Number of Participants With Medical Outcomes Study-Sleep Scale (MOS-SS)- Optimal Sleep at Week 12 | 64 Participants |
| Pramipexole 0.5 mg | Number of Participants With Medical Outcomes Study-Sleep Scale (MOS-SS)- Optimal Sleep at Week 12 | 77 Participants |
| Placebo | Number of Participants With Medical Outcomes Study-Sleep Scale (MOS-SS)- Optimal Sleep at Week 12 | 68 Participants |
Secondary
Profile of Mood State (POMS) at Week 12
POMS are participant-rated instrument comprising 6 sub-scales (tension-anxiety, depression-dejection, anger-hostility, vigor-activity, fatigue-inertia, and confusion-bewilderment) and each subscale comprising 5 items, on 'How you feel right now?' (Scale: 0=not at all, 1=a little, 2=moderately, 3=quite a bit, 4=extremely). All items were rated in the same direction except for vigor-activity. A total score is obtained for each scale. The range of total score is 0 - 100, with higher score indicating more mood disturbance.
Time frame: Week 12
Population: Data for this pre-specified outcome measure was collected and reported in individual participant listings but not statistically summarized for analysis due to lack of sufficient knowledge as how to analyze mood data inferentially in RLS population.
Secondary
Restless Legs Syndrome-Quality of Life Scale (RLS-QoL) at Week 12
RLS QoL: Participant rated instrument used to assess the impact of RLS on quality of life and health status function (symptom severity, daily activity, social functioning, sleep, concentrating and decision making, traveling, sexual activity, and work) yielding a summary score ranging from 0-100. Higher scores reflect better quality of life.
Time frame: Week 12
Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin 300 mg | Restless Legs Syndrome-Quality of Life Scale (RLS-QoL) at Week 12 | 77.75 Units on Scale | Standard Deviation 10.92 |
| Pramipexole 0.25 mg | Restless Legs Syndrome-Quality of Life Scale (RLS-QoL) at Week 12 | 73.33 Units on Scale | Standard Deviation 13.02 |
| Pramipexole 0.5 mg | Restless Legs Syndrome-Quality of Life Scale (RLS-QoL) at Week 12 | 75.48 Units on Scale | Standard Deviation 12.69 |
| Placebo | Restless Legs Syndrome-Quality of Life Scale (RLS-QoL) at Week 12 | 73.23 Units on Scale | Standard Deviation 13.98 |
Secondary
RLS-Next Day Impact (RLS-NDI)
The RLS-NDI is a participant-rated instrument designed to assess daytime performance as related to RLS and the participant's previous night's sleep. The instrument consists of 14 items that encompass 5 domains: tiredness; emotional functioning; social functioning; cognitive functioning; and activities of daily living. There is also 1 global item assessing overall well -being. Each item is scored on a 0-10 numeric rating scale. Total score is the sum of scores from question 1 to 14. The total score ranges from 0 to 140 where higher scores indicate a more severe impact.
Time frame: Baseline
Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin 300 mg | RLS-Next Day Impact (RLS-NDI) | 49.30 Units on a Scale | Standard Deviation 22.03 |
| Pramipexole 0.25 mg | RLS-Next Day Impact (RLS-NDI) | 51.90 Units on a Scale | Standard Deviation 18.62 |
| Pramipexole 0.5 mg | RLS-Next Day Impact (RLS-NDI) | 58.40 Units on a Scale | Standard Deviation 20.27 |
| Placebo | RLS-Next Day Impact (RLS-NDI) | 50.00 Units on a Scale | Standard Deviation 22.64 |
Secondary
Severity of Augmentation Symptoms at Week 12
ASRS measures severity of augmentation and consist of three items to be completed by clinician. Clinician would score participants' answers by comparing post-baseline evaluations to those at baseline. ASRS total score range: 0-24, with higher score indicating more severe augmentation.
Time frame: Week 12
Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin 300 mg | Severity of Augmentation Symptoms at Week 12 | 0.90 Units on a Scale | Standard Deviation 1.6 |
| Pramipexole 0.25 mg | Severity of Augmentation Symptoms at Week 12 | 1.60 Units on a Scale | Standard Deviation 2.29 |
| Pramipexole 0.5 mg | Severity of Augmentation Symptoms at Week 12 | 1.30 Units on a Scale | Standard Deviation 1.87 |
| Placebo | Severity of Augmentation Symptoms at Week 12 | 1.40 Units on a Scale | Standard Deviation 1.95 |
Secondary
Subjective Sleep Questionnaire (SSQ): Hours of Sleep Subscale Score at Week 12
SSQ: Participant-rated instrument used to assess previous night's sleep profile. It is used to measure sleep quantity and quality and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), total WASO (1 item), quality of sleep (1 item). Hours of sleep subscale: numerical rating completed by the participant 30 minutes after waking; recall period is the night before. Hours of sleep subscale score ranges from 0-16 hours. Higher value indicates better sleep.
Time frame: Week 12
Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin 300 mg | Subjective Sleep Questionnaire (SSQ): Hours of Sleep Subscale Score at Week 12 | 7.00 hours | Standard Deviation 1.05 |
| Pramipexole 0.25 mg | Subjective Sleep Questionnaire (SSQ): Hours of Sleep Subscale Score at Week 12 | 6.70 hours | Standard Deviation 1.19 |
| Pramipexole 0.5 mg | Subjective Sleep Questionnaire (SSQ): Hours of Sleep Subscale Score at Week 12 | 6.80 hours | Standard Deviation 1.09 |
| Placebo | Subjective Sleep Questionnaire (SSQ): Hours of Sleep Subscale Score at Week 12 | 6.70 hours | Standard Deviation 1.16 |
Secondary
Subjective Sleep Questionnaire (SSQ): Latency Subscale Score at Week 12
SSQ: Participant-rated instrument used to assess previous night's sleep profile. It is used to measure sleep quantity and quality and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), total WASO (1 item), quality of sleep (1 item). Latency subscale (in minutes): numerical rating completed by the participant 30 minutes after waking; recall period is the night before. Latency subscale score ranges from 0-840 minutes. Lower value indicates better sleep.
Time frame: Week 12
Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin 300 mg | Subjective Sleep Questionnaire (SSQ): Latency Subscale Score at Week 12 | 41.60 minutes | Standard Deviation 35.76 |
| Pramipexole 0.25 mg | Subjective Sleep Questionnaire (SSQ): Latency Subscale Score at Week 12 | 43.10 minutes | Standard Deviation 35.84 |
| Pramipexole 0.5 mg | Subjective Sleep Questionnaire (SSQ): Latency Subscale Score at Week 12 | 35.90 minutes | Standard Deviation 33.08 |
| Placebo | Subjective Sleep Questionnaire (SSQ): Latency Subscale Score at Week 12 | 47.70 minutes | Standard Deviation 44.89 |
Secondary
Subjective Sleep Questionnaire (SSQ): Number of Awakenings Subscale Score at Week 12
SSQ: Participant-rated instrument used to assess previous night's sleep profile. It is used to measure sleep quantity and quality and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), total WASO (1 item), quality of sleep (1 item). Number of awakenings subscale: numerical rating completed by the participant 30 minutes after waking; recall period is the night before. Number of awakenings subscale score ranges from 0-30. Lower value indicates better sleep.
Time frame: Week 12
Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin 300 mg | Subjective Sleep Questionnaire (SSQ): Number of Awakenings Subscale Score at Week 12 | 1.10 awakenings | Standard Deviation 1.14 |
| Pramipexole 0.25 mg | Subjective Sleep Questionnaire (SSQ): Number of Awakenings Subscale Score at Week 12 | 1.70 awakenings | Standard Deviation 1.22 |
| Pramipexole 0.5 mg | Subjective Sleep Questionnaire (SSQ): Number of Awakenings Subscale Score at Week 12 | 1.50 awakenings | Standard Deviation 1.08 |
| Placebo | Subjective Sleep Questionnaire (SSQ): Number of Awakenings Subscale Score at Week 12 | 1.80 awakenings | Standard Deviation 2.14 |
Secondary
Subjective Sleep Questionnaire (SSQ): Quality of Sleep Subscale Score at Week 12
SSQ: Participant-rated instrument used to assess previous night's sleep profile. It is used to measure sleep quantity and quality and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), total WASO (1 item), quality of sleep (1 item). Quality of sleep subscale: numerical rating completed by the participant 30 minutes after waking; recall period is the night before. Quality of sleep subscale score ranges from 0-100. Higher score indicates better quality of sleep.
Time frame: Week 12
Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin 300 mg | Subjective Sleep Questionnaire (SSQ): Quality of Sleep Subscale Score at Week 12 | 66.50 Units on a scale | Standard Deviation 20 |
| Pramipexole 0.25 mg | Subjective Sleep Questionnaire (SSQ): Quality of Sleep Subscale Score at Week 12 | 57.40 Units on a scale | Standard Deviation 19.83 |
| Pramipexole 0.5 mg | Subjective Sleep Questionnaire (SSQ): Quality of Sleep Subscale Score at Week 12 | 60.20 Units on a scale | Standard Deviation 19.43 |
| Placebo | Subjective Sleep Questionnaire (SSQ): Quality of Sleep Subscale Score at Week 12 | 57.70 Units on a scale | Standard Deviation 20.27 |
Secondary
Subjective Sleep Questionnaire (SSQ): Subjective Waking After Sleep Onset (WASO)
SSQ: Participant-rated instrument used to assess previous night's sleep profile. It is used to measure sleep quantity and quality and is comprised of 5 items yielding 5 subscale scores: latency (1 item), hours of sleep (1 item), number of awakenings (1 item), total WASO (1 item), quality of sleep (1 item). WASO is time spent awake from sleep onset to final awakening. Total WASO subscale (in minutes): numerical rating completed by the participant 30 minutes after waking; recall period is the night before. Total WASO subscale score ranges from 0-1440 minutes. Lower value indicates better sleep.
Time frame: Baseline
Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, the 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure for each group respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin 300 mg | Subjective Sleep Questionnaire (SSQ): Subjective Waking After Sleep Onset (WASO) | 90.60 minutes | Standard Deviation 76.1 |
| Pramipexole 0.25 mg | Subjective Sleep Questionnaire (SSQ): Subjective Waking After Sleep Onset (WASO) | 100.20 minutes | Standard Deviation 85.92 |
| Pramipexole 0.5 mg | Subjective Sleep Questionnaire (SSQ): Subjective Waking After Sleep Onset (WASO) | 83.90 minutes | Standard Deviation 77.35 |
| Placebo | Subjective Sleep Questionnaire (SSQ): Subjective Waking After Sleep Onset (WASO) | 79.50 minutes | Standard Deviation 69.85 |
Secondary
Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) at Week 12
WPAI: 6 question participant rated questionnaire to determine degree to which SHP affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 10 (completely affected/impaired). WPAI outcomes expressed as impairment percentages with higher numbers indicating greater impairment and less productivity.
Time frame: Week 12
Population: ITT population included all randomized participants who took at least 1 dose of study medication and had at least one post-randomization efficacy assessment on any efficacy scale. Here, 'n' is signifying those participants who were evaluable for particular category for each group respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin 300 mg | Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) at Week 12 | Overall work (n= 10, 7, 11, 10) | 6.00 Percentage of impairment | Standard Deviation 9.66 |
| Pregabalin 300 mg | Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) at Week 12 | Work time missed (n= 10, 7, 11, 10) | 0.00 Percentage of impairment | Standard Deviation 0 |
| Pregabalin 300 mg | Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) at Week 12 | Activity (n= 18, 22, 25, 20) | 12.20 Percentage of impairment | Standard Deviation 19.27 |
| Pramipexole 0.25 mg | Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) at Week 12 | Overall work (n= 10, 7, 11, 10) | 5.70 Percentage of impairment | Standard Deviation 11.34 |
| Pramipexole 0.25 mg | Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) at Week 12 | Work time missed (n= 10, 7, 11, 10) | 0.00 Percentage of impairment | Standard Deviation 0 |
| Pramipexole 0.25 mg | Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) at Week 12 | Activity (n= 18, 22, 25, 20) | 20.90 Percentage of impairment | Standard Deviation 24.28 |
| Pramipexole 0.5 mg | Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) at Week 12 | Work time missed (n= 10, 7, 11, 10) | 0.00 Percentage of impairment | Standard Deviation 0 |
| Pramipexole 0.5 mg | Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) at Week 12 | Activity (n= 18, 22, 25, 20) | 22.80 Percentage of impairment | Standard Deviation 23.01 |
| Pramipexole 0.5 mg | Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) at Week 12 | Overall work (n= 10, 7, 11, 10) | 9.10 Percentage of impairment | Standard Deviation 20.71 |
| Placebo | Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) at Week 12 | Work time missed (n= 10, 7, 11, 10) | 1.50 Percentage of impairment | Standard Deviation 3.62 |
| Placebo | Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) at Week 12 | Activity (n= 18, 22, 25, 20) | 23.00 Percentage of impairment | Standard Deviation 24.52 |
| Placebo | Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) at Week 12 | Overall work (n= 10, 7, 11, 10) | 14.60 Percentage of impairment | Standard Deviation 23.39 |