Table 1IRLS severity scale
Questions were rated by the patient, considering the symptoms of RLS over the previous 2 weeks; rating was from 4 to 0: (4) very severe, (3) severe, (2) moderate, (1) mild, (0) none, except for questions 3, 7, and 8
1. Overall, how would you rate the RLS discomfort in your legs or arms?
2.Overall, how would you rate the need to move around because of your RLS symptoms?
3. Overall, how much relief of your RLS arm or leg discomfort do you get from moving around?
Rating: (4) no relief, (3) slight relief, (2) moderate relief, (1) either complete or almost complete relief, (0) no RLS symptoms*
4. Overall, how severe is your sleep disturbance from your RLS symptoms?
5. How severe is your tiredness or sleepiness from your RLS symptoms?
6. Overall, how severe is your RLS as a whole?
7. How often do you get RLS symptoms?
Rating: (4) very severe (6-7 days a week), (3) severe (4-5 days a week), (2) moderate (2-3 days a week), (1) mild (1 day a week or less), (0) nonexistent *
8. When you have RLS symptoms, how severe are they on an average day?
Rating: (4) very severe (8 hours per 24-hour day or more), (3) severe (3-8 hours per 24-hour day), (2) moderate (1-3 hours per 24-hour day), (1) mild (less than 1 hour per 24-hour day), (0) nonexistent *
9.Overall, how severe is the impact of your RLS symptoms on your ability to carry out your daily affairs, for example, carrying out a satisfactory family, home, social, school, or work life?
10.How severe is your mood disturbance from your RLS symptoms — for example angry, depressed, sad, anxious, or irritable?
*Response options for questions 3, 7, and 8 were modified to further define severity. Question 3 was rated as (4) no relief, (3) slight relief, (2) moderate relief, (1) either complete or almost complete relief, (0) no RLS symptoms and therefore question does not apply. Question 7 was rated as (4) very severe (6-7 days a week), (3) severe (4-5 days a week), (2) moderate (2-3 days a week), (1) mild (1 day a week or less), (0) nonexistent. Question 8 was rated as (4) very severe (8 hours per 24-hour day or more), (3) severe (3-8 hours per 24-hour day), (2) moderate (1-3 hours per 24-hour day), (1) mild (less than 1 hour per 24-hour day), (0) nonexistent.
RLS = restless legs syndrome.
Table 2 Baseline characteristics of the patients*
Variable / Pergolide / Placebo / Totaln = 47 / n = 53 / n = 100
Sex, No. (%)
Female / 32 (68.1) / 28 (52.8) / 60 (60.0)
Male / 15 (31.9) / 25 (47.2) / 40 (40.0)
Age, years
Mean ± SD / 58.1 9.3 / 54.4 11.3 / 56.2 10.6
Age range, years [ No. (%)]
<51 / 13 (27.7) / 21 (39.6) / 34 (34.0)
≥51 - <66 / 26 (55.3) / 24 (45.3) / 50 (50.0)
66 / 8 (17.0) / 8 (15.1) / 16 (16.0)
Duration of disease, months
Mean ± SD / 195.5 180.6 / 226.2 166.9 / 211.8 173.3
*There were no statistically significant differences between the pergolide and placebo groups.
Table 3 Treatment effects of pergolide (mean dose, 0.40 mg/day) and placebo after 6 weeks
N / Baseline (mean SD) / 6 weeks (mean SD) / p-value*Pergolide / Placebo / Pergolide / Placebo / Pergolide / Placebo
Primary efficacy measures
PLMS arousal index (PLMS with arousal per hour asleep) / 39 / 42 / 15.2 9.9 / 18.2 23.2 / 2.6 3.6 / 14.6 14.5 / 0.004
Sleep efficiency
(% TST per total time in bed) / 39 / 42 / 71.3 12.5 / 70.3 14.8 / 82.6 11.1 / 76.4 13.5 / 0.196
Secondary efficacy measures
Total sleep time (min) / 39 / 42 / 339.2 63.0 / 334.2 74.5 / 395.4 63.2 / 363.0 71.2 / 0.145
PLM Index (number of PLM per hour in bed) / 39 / 42 / 39.6 24.1 / 44.2 35.1 / 9.0 10.6 / 45.0 37.1 / <0.001
IRLS severity scale / 46 / 51 / 23.7 6.1 / 25.0 5.6 / 11.5 7.7 / 23.2 7.8 / <0.001
IRLS severity scale–item 9 / 46 / 51 / 1.8 1.1 / 1.7 1.0 / 0.6 0.8 / 1.5 1.1 / <0.001
Physician’s CGI rating1 / 43 / 51 / 4.4 1.1 / 4.6 1.1 / 2.7 1.3 / 4.2 1.5 / <0.001
CGI Improvement2 / 43 / 51 / -- / -- / 2.1 1.2 / 3.4 1.1 / <0.001
PGI improvement rating2 / 43 / 51 / -- / -- / 2.0 1.1 / 3.4 1.1 / <0.001
Patient diary measures
Subjective sleep quality3 / 40 / 47 / 3.7 0.8 / 3.6 1.0 / 4.8 1.0 / 3.8 0.8 / <0.001
Subjective sleep efficiency
(% TST per total time in bed) / 37 / 44 / 64.2 19.7 / 60.8 22.0 / 80.8 12.8 / 67.7 19.3 / 0.019
17 = amongst the most severely ill patients
27 = very much worse
37 = excellent
*Comparison of least-squares means from ANOVA; p-value for change from baseline.
CGI = Clinical Global Impressions; PLM = periodic limb movement; PLMS = periodic limb movement in sleep; RLS = restless legs syndrome; TST = total sleep time.
Table 4 Treatment effects of pergolide and placebo at one year*
Efficacy measure / Treatment group / N / Mean ± SD / Change at one year end point (pooled) / p-value†N / Mean ± SD
PLMS arousal index (PLMS with arousal per hour asleep) / Blinded pergolide / 29 / -14.4 ± 10.5 / 34 / -13.1 ± 11.1 / 0.028
Pergolide/open pergolide / 5 / -5.6 ± 12.9
Blinded placebo / 5 / -23.5 ± 46.6 / 39 / -4.0 ± 19.5
Placebo/open pergolide (6 wks) / 34 / -1.1 ± 10.5
Sleep efficiency (% TST per total TIB) / Blinded pergolide / 30 / 10.6 ± 12.9 / 35 / 11.3 ± 13.6 / 0.156
Pergolide/open pergolide / 5 / 15.3 ± 18.4
Blinded placebo / 5 / 3.2 ± 6.9 / 39 / 4.4 ± 18.9
Placebo/open pergolide (6 wks) / 34 / 4.5 ± 20.1
PLM Index (number per hour in bed) / Blinded pergolide / 29 / -32.9 ± 22.6 / 34 / -30.9 ± 23.2 / <0.0001
Pergolide/open pergolide / 5 / -19.6 ± 26.4
Blinded placebo / 5 / -15.3 ± 26.0 / 39 / 2.5 ± 25.2
Placebo/open pergolide (6 wks) / 34 / 5.1 ± 24.4
*Blinded and open-label treatment groups pooled and Week 6 results carried forward for patients who switched therapy after phase 1 (placebo nonresponders).
†Comparison of least-squares means from ANOVA for pooled blinded and open-label pergolide and placebo groups (therapy and country in the model).
PLM = periodic limb movement; PLMS = periodic limb movement in sleep; TIB = time in bed; TST = total sleep time.
Table 5 Treatment-emergent adverse events reported during the first 6 weeks*
Event / Pergolide (n=46) / Placebo(n=53) / p-value†
Overall
/ 31 (67.4%) / 29 (54.7%) / p=0.198Nausea
/ 19 (41.3%) / 8 (15.1%) / p=0.003Headache / 7 (15.2%) / 1 (1.9%) / p=0.015
Abdominal Pain / 4 (8.7%) / 2 (3.8%) / p=0.306
Asthenia / 4 (8.7%) / 3 (5.7%) / p=0.557
Postural hypotension / 3 (6.5%) / 0
Vomiting / 3 (6.5%) / 0
Dizziness / 3 (6.5%) / 2 (3.8%) / p=0.553
* Only includes those events reported by 5% or more of patients in either treatment group
† Chi Square test, only given where 4 or more patients have the event
Table 6 Treatment-emergent adverse events reported during the entire 12-month study period
Event* / Double-blindpergolide†
n = 39 / Double-blind
placebo
n = 17 / Open-label
pergolide‡
n = 43
Overall / 34 (87.2%) / 13 (76.5%) / 34 (79.1%)
Nausea / 23 (59.0%) / 5 (29.4%) / 22 (51.2%)
Headache / 8 (20.5%) / 1 (5.9%) / 7 (16.3%)
Asthenia / 7 (17.9%) / 0 / 4 (9.3%)
Rhinitis / 7 (17.9%) / 1 (5.9%) / 4 (9.3%)
Dizziness / 5 (12.8%) / 1 (5.9%) / 5 (11.6%)
Postural hypotension / 5 (12.8%) / 0 / 2 (4.7%)
Abdominal pain / 4 (10.3%) / 2 (11.8%) / 7 (16.3%)
Vomiting / 4 (10.3%) / 0 / 7 (16.3%)
Pharyngitis / 4 (10.3%) / 0 / 2 (4.7%)
Flu syndrome / 1 (2.6%) / 2 (11.8%) / 2 (4.7%)
Pain / 1 (2.6%) / 4 (23.5%) / 1 (2.3%)
*Events reported by 10% or more of patients in any group.
†One pergolide patient was not assessed after baseline.
‡Seven patients were randomized to pergolide and 36 to placebo. The baseline period is the first 6 weeks for these placebo patients.
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