Trial Outcomes & Findings for Long-term Efficacy, Safety and Tolerability of Pramipexole in Patients With Idiopathic Moderate to Severe Restless Legs Syndrome (RLS) (NCT NCT00472199)
NCT ID: NCT00472199
Last Updated: 2014-06-27
Results Overview
IRLS total score ranging from 0 (no RLS symptoms) to 40 (very severe RLS symptoms)
COMPLETED
PHASE4
331 participants
Baseline and 26 weeks
2014-06-27
Participant Flow
Of 331 patients enrolled, 329 were treated with study drug. Two patients were randomized, but before their first intake of trial medication they decided to not participate in the study.
Participant milestones
| Measure |
Pramipexole
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Overall Study
STARTED
|
166
|
163
|
|
Overall Study
COMPLETED
|
131
|
103
|
|
Overall Study
NOT COMPLETED
|
35
|
60
|
Reasons for withdrawal
| Measure |
Pramipexole
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Overall Study
Adverse Event
|
19
|
23
|
|
Overall Study
Lack of Efficacy
|
4
|
25
|
|
Overall Study
Lost to Follow-up
|
2
|
4
|
|
Overall Study
Protocol Violation
|
3
|
2
|
|
Overall Study
Withdrawal by Subject
|
6
|
5
|
|
Overall Study
personal reason
|
0
|
1
|
|
Overall Study
patient was asymptomatic
|
1
|
0
|
Baseline Characteristics
Long-term Efficacy, Safety and Tolerability of Pramipexole in Patients With Idiopathic Moderate to Severe Restless Legs Syndrome (RLS)
Baseline characteristics by cohort
| Measure |
Pramipexole
n=166 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=163 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Total
n=329 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
57.9 years
STANDARD_DEVIATION 12.7 • n=99 Participants
|
55.8 years
STANDARD_DEVIATION 11.4 • n=107 Participants
|
56.8 years
STANDARD_DEVIATION 12.1 • n=206 Participants
|
|
Sex: Female, Male
Female
|
102 Participants
n=99 Participants
|
94 Participants
n=107 Participants
|
196 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
64 Participants
n=99 Participants
|
69 Participants
n=107 Participants
|
133 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline and 26 weeksPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
IRLS total score ranging from 0 (no RLS symptoms) to 40 (very severe RLS symptoms)
Outcome measures
| Measure |
Pramipexole
n=162 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=159 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Total Score After 26 Weeks
|
-13.7 Scores on a scale
Standard Error 0.8
|
-11.1 Scores on a scale
Standard Error 0.8
|
SECONDARY outcome
Timeframe: after 26 weeks of treatmentPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values.
CGI-I scores ranging from '1' (very much improved) to '7' (very much worse), CGI-I responder have scoring 1 or 2 (at least much improved)
Outcome measures
| Measure |
Pramipexole
n=162 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=159 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Clinical Global Impression - Global Improvement (CGI-I) Responder Rate
CGI-I responder (at least much improved)
|
111 participants
|
80 participants
|
|
Clinical Global Impression - Global Improvement (CGI-I) Responder Rate
CGI-I non-responder
|
51 participants
|
79 participants
|
SECONDARY outcome
Timeframe: after 26 weeks of treatmentPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
IRLS response was defined as at least 50% reduction in IRLS total score from baseline. IRLS total score ranging from 0 (no RLS symptoms) to 40 (very severe symptoms)
Outcome measures
| Measure |
Pramipexole
n=162 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=159 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
International Restless Legs Syndrome (IRLS) Study Group Rating Scale Responder Rate
IRLS responder
|
95 participants
|
68 participants
|
|
International Restless Legs Syndrome (IRLS) Study Group Rating Scale Responder Rate
IRLS non-responder
|
67 participants
|
91 participants
|
SECONDARY outcome
Timeframe: after 26 weeks of treatmentPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
PGI scores ranging from '1' (very much better) to '7' (very much worse), PGI responder have scoring 1 or 2 (at least much better)
Outcome measures
| Measure |
Pramipexole
n=162 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=159 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Patient Global Impression (PGI) Responder Rate
PGI responder (much better or very much better)
|
101 participants
|
70 participants
|
|
Patient Global Impression (PGI) Responder Rate
PGI non-responder
|
61 participants
|
89 participants
|
SECONDARY outcome
Timeframe: baseline and 26 weeks of treatmentPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
The score is an 11-point Likert scale, ranging from "none/not at all" (0) to "very severe" (10), to reflect the patient's condition during the previous week
Outcome measures
| Measure |
Pramipexole
n=162 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=159 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Change From Baseline in Restless Legs Syndrome-6 (RLS-6) Score "Satisfaction With Sleep" After 26 Weeks
|
-2.5 Scores on a scale
Interval -5.0 to 0.0
|
-2 Scores on a scale
Interval -4.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline and 26 weeks of treatmentPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
The score is an 11-point Likert scale, ranging from "none/not at all" (0) to "very severe" (10), to reflect the patient's condition during the previous week
Outcome measures
| Measure |
Pramipexole
n=162 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=159 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Change From Baseline in RLS-6 Score "Severity Falling Asleep" After 26 Weeks
|
-3 Scores on a scale
Interval -5.0 to 0.0
|
-1 Scores on a scale
Interval -4.0 to 0.0
|
SECONDARY outcome
Timeframe: baseline and 26 weeks of treatmentPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
The question was rated on an 11-point Likert scale, ranging from "none/not at all" (0) to "very severe" (10), to reflect the patient's condition during the previous week
Outcome measures
| Measure |
Pramipexole
n=162 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=159 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Change From Baseline in RLS-6 Score "Severity During the Night" After 26 Weeks
|
-3 Scores on a scale
Interval -5.0 to 0.0
|
-2 Scores on a scale
Interval -5.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline and 26 weeks of treatmentPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
The score is an 11-point Likert scale, ranging from "none/not at all" (0) to "very severe" (10), to reflect the patient's condition during the previous week
Outcome measures
| Measure |
Pramipexole
n=162 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=159 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Change From Baseline in RLS-6 Score "Severity During the Day When at Rest" After 26 Weeks
|
-3 Scores on a scale
Interval -5.0 to 0.0
|
-1 Scores on a scale
Interval -4.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline and 26 weeks of treatmentPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
The score is an 11-point Likert scale, ranging from "none/not at all" (0) to "very severe" (10), to reflect the patient's condition during the previous week
Outcome measures
| Measure |
Pramipexole
n=162 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=159 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Change From Baseline RLS-6 Score "Severity During the Day Engaged in Activities" After 26 Weeks
|
0 Scores on a scale
Interval -1.0 to 0.0
|
0 Scores on a scale
Interval -1.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline and 26 weeks of treatmentPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
The score is an 11-point Likert scale, ranging from "none/not at all" (0) to "very severe" (10), to reflect the patient's condition during the previous week
Outcome measures
| Measure |
Pramipexole
n=162 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=159 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Change From Baseline in RLS-6 Score "Tired or Sleepy During the Day" After 26 Weeks
|
-1 Scores on a scale
Interval -3.0 to 0.0
|
-1 Scores on a scale
Interval -3.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline and 26 weeks of treatmentPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
Mood disturbance associated with RLS symptoms ranging from 0 (none) to 4 (very severe)
Outcome measures
| Measure |
Pramipexole
n=162 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=159 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Change From Baseline in IRLS Mood Disturbance Score (Item 10) After 26 Weeks
|
-1 scores on a scale
Interval -2.0 to 0.0
|
-1 scores on a scale
Interval -2.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline and 26 weeks of treatmentPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
The scale measures pain on a continuous 100 mm axis ranging from no pain (0 mm) to unbearable pain (100 mm)
Outcome measures
| Measure |
Pramipexole
n=162 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=158 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Change From Baseline in Visual Analogue Scale (VAS) Score for Pain in Limbs After 26 Weeks
|
-26 Scores on a scale
Interval -47.0 to -5.0
|
-15 Scores on a scale
Interval -46.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline and 26 weeks of treatmentPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
RLS QoL total score ranging from 0 to 100 with higher values indicating better quality of life
Outcome measures
| Measure |
Pramipexole
n=157 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=153 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Change From Baseline in Quality of Life in RLS (RLS QoL) Score After 26 Weeks
|
15 Scores on a scale
Interval 5.0 to 25.0
|
12.5 Scores on a scale
Interval 2.5 to 27.5
|
SECONDARY outcome
Timeframe: Baseline and 26 weeksPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
Score ranging from 0 to 100 with higher scores indicating less bodily pain
Outcome measures
| Measure |
Pramipexole
n=157 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=152 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Change From Baseline in Short Form-36 (SF-36) Dimension Bodily Pain After 26 Weeks
|
12 Scores on a scale
Interval 0.0 to 31.0
|
9 Scores on a scale
Interval -1.0 to 24.5
|
SECONDARY outcome
Timeframe: Baseline and 26 weeksPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
Score ranging from 0 to 100 with higher scores indicating better health status
Outcome measures
| Measure |
Pramipexole
n=155 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=152 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Change From Baseline in SF-36 Dimension General Health After 26 Weeks
|
0 Scores on a scale
Interval -5.0 to 10.0
|
0 Scores on a scale
Interval -5.0 to 10.0
|
SECONDARY outcome
Timeframe: Baseline and 26 weeksPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
Score ranging from 0 to 100 with higher scores indicating better mental health
Outcome measures
| Measure |
Pramipexole
n=155 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=152 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Change From Baseline in SF-36 Dimension Mental Health After 26 Weeks
|
5 Scores on a scale
Interval -5.0 to 15.0
|
5 Scores on a scale
Interval -5.0 to 10.0
|
SECONDARY outcome
Timeframe: Baseline and 26 weeksPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
Score ranging from 0 to 100 with higher scores indicating better physical functioning
Outcome measures
| Measure |
Pramipexole
n=156 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=152 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Change From Baseline in SF-36 Dimension Physical Functioning After 26 Weeks
|
0 Scores on a scale
Interval 0.0 to 10.0
|
0 Scores on a scale
Interval -5.0 to 10.0
|
SECONDARY outcome
Timeframe: Baseline and 26 weeksPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
Score ranging from 0 to 100 with higher scores indicating less limitations due to emotional problems
Outcome measures
| Measure |
Pramipexole
n=156 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=152 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Change From Baseline in SF-36 Dimension Role Limitations Due to Emotional Problems After 26 Weeks
|
0 Scores on a scale
Interval -8.3 to 16.7
|
0 Scores on a scale
Interval 0.0 to 16.7
|
SECONDARY outcome
Timeframe: Baseline and 26 weeksPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
Score ranging from 0 to 100 with higher scores indicating less limitations due to physical problems
Outcome measures
| Measure |
Pramipexole
n=156 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=152 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Change From Baseline in SF-36 Dimension Role Limitations Due to Physical Problems After 26 Weeks
|
6.3 Scores on a scale
Interval 0.0 to 18.8
|
6.3 Scores on a scale
Interval 0.0 to 18.8
|
SECONDARY outcome
Timeframe: Baseline and 26 weeksPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
Score ranging from 0 to 100 with higher scores indicating better social functioning
Outcome measures
| Measure |
Pramipexole
n=157 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=152 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Change From Baseline in SF-36 Dimension Social Functioning After 26 Weeks
|
0 Scores on a scale
Interval 0.0 to 12.5
|
0 Scores on a scale
Interval 0.0 to 25.0
|
SECONDARY outcome
Timeframe: Baseline and 26 weeksPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
Score ranging from 0 to 100 with higher scores indicating better vitality
Outcome measures
| Measure |
Pramipexole
n=155 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=152 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Change From Baseline in SF-36 Dimension Vitality After 26 Weeks
|
6.3 Scores on a scale
Interval 0.0 to 18.8
|
3.1 Scores on a scale
Interval -6.3 to 12.5
|
SECONDARY outcome
Timeframe: Baseline and 26 weeksPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
Score ranging from 0 to 100 with higher scores indicating better health
Outcome measures
| Measure |
Pramipexole
n=155 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=152 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Change From Baseline in SF-36 Dimension Mental Component Summary After 26 Weeks
|
1.7 Scores on a scale
Interval -2.4 to 8.3
|
1.9 Scores on a scale
Interval -2.3 to 6.7
|
SECONDARY outcome
Timeframe: Baseline and 26 weeksPopulation: Intent to treat analysis. Number of randomized patients with a baseline and at least one non-missing post-baseline measure. Imputation by last observation carried forward (LOCF) for post-baseline values
Score ranging from 0 to 100 with higher scores indicating better health
Outcome measures
| Measure |
Pramipexole
n=155 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=152 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Change From Baseline in SF-36 Dimension Physical Component Summary After 26 Weeks
|
2.1 Scores on a scale
Interval -0.5 to 7.5
|
2 Scores on a scale
Interval -2.0 to 5.9
|
SECONDARY outcome
Timeframe: after at least 4 weeks of treatmentPopulation: Treated Set and where patients received study medication for at least 4 weeks (Treated Set includes all patients who were documented to have taken at least one dose of of treatment)
Augmentation is a worsening of RLS symptoms and may manifest as increased severity and the involvement of other extremities or as a shift of RLS symptoms to a time period that is 2 or more hours earlier than was typical of the time of symptom onset during the initial course of beneficial stable treatment or the state before recently starting treatment.
Outcome measures
| Measure |
Pramipexole
n=152 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=149 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Diagnosis of Classified Augmentation According to Independent Expert Panel
|
18 participants
|
14 participants
|
SECONDARY outcome
Timeframe: after at least 1 week of treatment discontinuationPopulation: Treated Set, all patients who were documented to have taken at least one dose of study medication
Worsening of RLS symptoms, in comparison to baseline, following abrupt treatment discontinuation (for patients with no added RLS therapy after study drug discontinuation). Assessment of worsening of RLS was based on the IRLS total score assessed 7 ± 1 days after treatment discontinuation (the end of the study or premature discontinuation) compared with that at baseline. Analysis considered the number of patients experiencing a clinically relevant deterioration of ≥4 points in total IRLS score 7 ± 1 days after discontinuation of trial medication compared with baseline.
Outcome measures
| Measure |
Pramipexole
n=135 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=133 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Worsening of RLS Symptoms (by at Least 4 Points in the IRLS Total Score Compared to Baseline) After Treatment Discontinuation
|
14 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: Treated Set, all patients who were documented to have taken at least one dose of study medication
Outcome measures
| Measure |
Pramipexole
n=166 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=163 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Baseline, Week 26 Mean Supine Systolic Blood Pressure
Baseline
|
133.4 mm Hg
Standard Deviation 16.9
|
132.7 mm Hg
Standard Deviation 18.4
|
|
Baseline, Week 26 Mean Supine Systolic Blood Pressure
Week 26
|
132.3 mm Hg
Standard Deviation 16.4
|
132.2 mm Hg
Standard Deviation 16.5
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: Treated Set, all patients who were documented to have taken at least one dose of study medication
Outcome measures
| Measure |
Pramipexole
n=166 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=163 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Baseline, Week 26 Mean Standing Systolic Blood Pressure
Baseline
|
132.6 mm Hg
Standard Deviation 17.3
|
130.6 mm Hg
Standard Deviation 18.2
|
|
Baseline, Week 26 Mean Standing Systolic Blood Pressure
Week 26
|
132.4 mm Hg
Standard Deviation 18.2
|
130.1 mm Hg
Standard Deviation 17.1
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: Treated Set, all patients who were documented to have taken at least one dose of study medication
Outcome measures
| Measure |
Pramipexole
n=166 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=163 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Baseline, Week 26 Mean Supine Diastolic Blood Pressure
Baseline
|
79.2 mm Hg
Standard Deviation 9.7
|
79.6 mm Hg
Standard Deviation 9.7
|
|
Baseline, Week 26 Mean Supine Diastolic Blood Pressure
Week 26
|
78.3 mm Hg
Standard Deviation 9.7
|
79.5 mm Hg
Standard Deviation 9.4
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: Treated Set, all patients who were documented to have taken at least one dose of study medication
Outcome measures
| Measure |
Pramipexole
n=166 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=163 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Baseline, Week 26 Mean Standing Diastolic Blood Pressure
Baseline
|
82.7 mm Hg
Standard Deviation 10.5
|
81.7 mm Hg
Standard Deviation 10.7
|
|
Baseline, Week 26 Mean Standing Diastolic Blood Pressure
Week 26
|
80.5 mm Hg
Standard Deviation 10.6
|
80.8 mm Hg
Standard Deviation 10.0
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: Treated Set, all patients who were documented to have taken at least one dose of study medication
Outcome measures
| Measure |
Pramipexole
n=166 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=163 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Baseline, Week 26 Mean Supine Pulse Rate
Baseline
|
68.5 bpm
Standard Deviation 9.6
|
68.7 bpm
Standard Deviation 10.6
|
|
Baseline, Week 26 Mean Supine Pulse Rate
Week 26
|
69.1 bpm
Standard Deviation 8.9
|
68.3 bpm
Standard Deviation 10.6
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: Treated Set, all patients who were documented to have taken at least one dose of study medication
Outcome measures
| Measure |
Pramipexole
n=166 Participants
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=163 Participants
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Baseline, Week 26 Mean Standing Pulse Rate
Baseline
|
74.6 bpm
Standard Deviation 10.2
|
74.0 bpm
Standard Deviation 10.7
|
|
Baseline, Week 26 Mean Standing Pulse Rate
Week 26
|
74.1 bpm
Standard Deviation 8.9
|
75.0 bpm
Standard Deviation 10.6
|
Adverse Events
Pramipexole
Placebo
Serious adverse events
| Measure |
Pramipexole
n=166 participants at risk
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=163 participants at risk
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Infections and infestations
Appendicitis
|
0.00%
0/166 • 26 weeks
|
0.61%
1/163 • 26 weeks
|
|
Infections and infestations
Urinary tract infection
|
0.60%
1/166 • 26 weeks
|
0.00%
0/163 • 26 weeks
|
|
Infections and infestations
Viral infection
|
0.00%
0/166 • 26 weeks
|
0.61%
1/163 • 26 weeks
|
|
Cardiac disorders
Myocardial infarction
|
0.60%
1/166 • 26 weeks
|
0.00%
0/163 • 26 weeks
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/166 • 26 weeks
|
0.61%
1/163 • 26 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.60%
1/166 • 26 weeks
|
0.00%
0/163 • 26 weeks
|
|
Gastrointestinal disorders
Crohn's disease
|
0.00%
0/166 • 26 weeks
|
0.61%
1/163 • 26 weeks
|
|
Gastrointestinal disorders
Haemorrhoidal haemorrhage
|
0.60%
1/166 • 26 weeks
|
0.00%
0/163 • 26 weeks
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/166 • 26 weeks
|
0.61%
1/163 • 26 weeks
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.60%
1/166 • 26 weeks
|
0.00%
0/163 • 26 weeks
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.60%
1/166 • 26 weeks
|
0.00%
0/163 • 26 weeks
|
|
Reproductive system and breast disorders
Uterine prolapse
|
0.60%
1/166 • 26 weeks
|
0.00%
0/163 • 26 weeks
|
|
Injury, poisoning and procedural complications
Extradural haematoma
|
0.60%
1/166 • 26 weeks
|
0.00%
0/163 • 26 weeks
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.60%
1/166 • 26 weeks
|
0.00%
0/163 • 26 weeks
|
Other adverse events
| Measure |
Pramipexole
n=166 participants at risk
4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase the dose to 0.25mg and to further increase or decrease the dose in steps to 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
Placebo
n=163 participants at risk
4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. mode of administration: Oral, once daily in the evening (2 to 3 hours before bedtime) form: tablets
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
14.5%
24/166 • 26 weeks
|
3.7%
6/163 • 26 weeks
|
|
General disorders
Fatigue
|
10.8%
18/166 • 26 weeks
|
9.2%
15/163 • 26 weeks
|
|
Nervous system disorders
Headache
|
7.8%
13/166 • 26 weeks
|
10.4%
17/163 • 26 weeks
|
|
Nervous system disorders
Restless legs syndrome
|
6.6%
11/166 • 26 weeks
|
6.7%
11/163 • 26 weeks
|
|
Nervous system disorders
Somnolence
|
6.6%
11/166 • 26 weeks
|
4.9%
8/163 • 26 weeks
|
|
Infections and infestations
Nasopharyngitis
|
4.2%
7/166 • 26 weeks
|
6.1%
10/163 • 26 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
6.0%
10/166 • 26 weeks
|
2.5%
4/163 • 26 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.4%
9/166 • 26 weeks
|
1.2%
2/163 • 26 weeks
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
- Publication restrictions are in place
Restriction type: OTHER