Long-term Efficacy, Safety and Tolerability of Pramipexole in Patients With Idiopathic Moderate to Severe Restless Legs Syndrome (RLS)
- Registration Number
- NCT00472199
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The primary objective of the current study will be the evaluation of long-term efficacy of a 26-weeks treatment with pramipexole in patients with idiopathic moderate to severe Restless Legs Syndrome (RLS) in comparison to placebo.
The key secondary objectives are to assess the effects on clinical global impressions - global improvement (CGI-I) (based on CGI-I responder rate) and on RLS (based on IRLS responder rate) for 26 weeks under pramipexole in comparison to placebo. Further secondary objectives are to investigate the incidence and severity of augmentation and rebound and to assess the effects on patient global impression (PGI) (based on PGI responder rate), on RLS symptoms (based on the RLS-6 scales), on associated mood disturbance (based on item 10 of the IRLS), on pain in limbs (based on a visual analogue scale (VAS)), on quality of life in RLS (based on Johns Hopkins RLS-QoL), on general quality of life Short Form 36 (SF-36) and on safety (based on adverse events (AE) profile) of pramipexole in comparison to placebo.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 331
- Written informed consent consistent with International Conference on Harmonization - Good Clinical Practice (ICH-GCP) and local Institutional Review Board/Independent Ethics Committee (IRB/IEC) requirements obtained prior to any study procedures being performed and the ability and willingness to comply with study treatment regimen and to attend study assessments
- Male or female out-patients aged 18-85 years
- Diagnosis of idiopathic RLS according to the clinical RLS criteria of the International Restless Legs Syndrome Study Group (IRLSSG) [P03-03355]. All four criteria must be present to fulfil the diagnosis of RLS.
- RLS symptoms present at least 2 to 3 days per week during the last 3 months prior to baseline (Visit 2)
- IRLS total score >15 at baseline (Visit 2)
- Women of child-bearing potential (i.e. premenopausal women, or postmenopausal women less than 6 months after last menses) who do not use during the clinical trial an adequate method of contraception such as: double barrier protection (e.g. diaphragm or condom and spermicide), intrauterine device, hormonal therapy (oral, injectable, or subcutaneous), or partner's surgical sterilization
- Any woman of child-bearing potential not having a negative pregnancy test at screening
- Breastfeeding women
- Patients with known hypersensitivity to pramipexole or any other component of the investigational product or placebo tablets
- Diagnosis of augmentation under previous pharmacological RLS treatment
- Concomitant or previous pharmacologic therapy as follows: Any intake of dopamine agonists within 14 days prior to baseline (Visit 2); Any intake of levodopa within 14 days prior to baseline (Visit 2); Unsuccessful prior treatment with non-ergot dopamine agonists (e.g. pramipexole, ropinirole);
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo 4 weeks of flexible dose-titration as for the investigational product; with the dose subsequently fixed for 22 weeks. Pramipexole Pramipexole 4 weeks of flexible dose-titration (to optimise efficacy and tolerability), starting at 0.125 mg once daily with the potential to increase or decrease the dose in steps to 0.25 mg, 0.5 mg and 0.75 mg, with the final dose level subsequently fixed for 22 weeks.
- Primary Outcome Measures
Name Time Method Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Total Score After 26 Weeks Baseline and 26 weeks IRLS total score ranging from 0 (no RLS symptoms) to 40 (very severe RLS symptoms)
- Secondary Outcome Measures
Name Time Method Change From Baseline in SF-36 Dimension Social Functioning After 26 Weeks Baseline and 26 weeks Score ranging from 0 to 100 with higher scores indicating better social functioning
Clinical Global Impression - Global Improvement (CGI-I) Responder Rate after 26 weeks of treatment CGI-I scores ranging from '1' (very much improved) to '7' (very much worse), CGI-I responder have scoring 1 or 2 (at least much improved)
International Restless Legs Syndrome (IRLS) Study Group Rating Scale Responder Rate after 26 weeks of treatment IRLS response was defined as at least 50% reduction in IRLS total score from baseline. IRLS total score ranging from 0 (no RLS symptoms) to 40 (very severe symptoms)
Patient Global Impression (PGI) Responder Rate after 26 weeks of treatment PGI scores ranging from '1' (very much better) to '7' (very much worse), PGI responder have scoring 1 or 2 (at least much better)
Change From Baseline in Restless Legs Syndrome-6 (RLS-6) Score "Satisfaction With Sleep" After 26 Weeks baseline and 26 weeks of treatment The score is an 11-point Likert scale, ranging from "none/not at all" (0) to "very severe" (10), to reflect the patient's condition during the previous week
Change From Baseline in RLS-6 Score "Severity Falling Asleep" After 26 Weeks Baseline and 26 weeks of treatment The score is an 11-point Likert scale, ranging from "none/not at all" (0) to "very severe" (10), to reflect the patient's condition during the previous week
Change From Baseline in RLS-6 Score "Severity During the Night" After 26 Weeks baseline and 26 weeks of treatment The question was rated on an 11-point Likert scale, ranging from "none/not at all" (0) to "very severe" (10), to reflect the patient's condition during the previous week
Change From Baseline in RLS-6 Score "Severity During the Day When at Rest" After 26 Weeks Baseline and 26 weeks of treatment The score is an 11-point Likert scale, ranging from "none/not at all" (0) to "very severe" (10), to reflect the patient's condition during the previous week
Change From Baseline RLS-6 Score "Severity During the Day Engaged in Activities" After 26 Weeks Baseline and 26 weeks of treatment The score is an 11-point Likert scale, ranging from "none/not at all" (0) to "very severe" (10), to reflect the patient's condition during the previous week
Change From Baseline in RLS-6 Score "Tired or Sleepy During the Day" After 26 Weeks Baseline and 26 weeks of treatment The score is an 11-point Likert scale, ranging from "none/not at all" (0) to "very severe" (10), to reflect the patient's condition during the previous week
Change From Baseline in IRLS Mood Disturbance Score (Item 10) After 26 Weeks Baseline and 26 weeks of treatment Mood disturbance associated with RLS symptoms ranging from 0 (none) to 4 (very severe)
Change From Baseline in Visual Analogue Scale (VAS) Score for Pain in Limbs After 26 Weeks Baseline and 26 weeks of treatment The scale measures pain on a continuous 100 mm axis ranging from no pain (0 mm) to unbearable pain (100 mm)
Change From Baseline in Quality of Life in RLS (RLS QoL) Score After 26 Weeks Baseline and 26 weeks of treatment RLS QoL total score ranging from 0 to 100 with higher values indicating better quality of life
Change From Baseline in Short Form-36 (SF-36) Dimension Bodily Pain After 26 Weeks Baseline and 26 weeks Score ranging from 0 to 100 with higher scores indicating less bodily pain
Change From Baseline in SF-36 Dimension General Health After 26 Weeks Baseline and 26 weeks Score ranging from 0 to 100 with higher scores indicating better health status
Change From Baseline in SF-36 Dimension Mental Health After 26 Weeks Baseline and 26 weeks Score ranging from 0 to 100 with higher scores indicating better mental health
Change From Baseline in SF-36 Dimension Physical Functioning After 26 Weeks Baseline and 26 weeks Score ranging from 0 to 100 with higher scores indicating better physical functioning
Change From Baseline in SF-36 Dimension Role Limitations Due to Emotional Problems After 26 Weeks Baseline and 26 weeks Score ranging from 0 to 100 with higher scores indicating less limitations due to emotional problems
Change From Baseline in SF-36 Dimension Role Limitations Due to Physical Problems After 26 Weeks Baseline and 26 weeks Score ranging from 0 to 100 with higher scores indicating less limitations due to physical problems
Change From Baseline in SF-36 Dimension Vitality After 26 Weeks Baseline and 26 weeks Score ranging from 0 to 100 with higher scores indicating better vitality
Change From Baseline in SF-36 Dimension Mental Component Summary After 26 Weeks Baseline and 26 weeks Score ranging from 0 to 100 with higher scores indicating better health
Change From Baseline in SF-36 Dimension Physical Component Summary After 26 Weeks Baseline and 26 weeks Score ranging from 0 to 100 with higher scores indicating better health
Diagnosis of Classified Augmentation According to Independent Expert Panel after at least 4 weeks of treatment Augmentation is a worsening of RLS symptoms and may manifest as increased severity and the involvement of other extremities or as a shift of RLS symptoms to a time period that is 2 or more hours earlier than was typical of the time of symptom onset during the initial course of beneficial stable treatment or the state before recently starting treatment.
Worsening of RLS Symptoms (by at Least 4 Points in the IRLS Total Score Compared to Baseline) After Treatment Discontinuation after at least 1 week of treatment discontinuation Worsening of RLS symptoms, in comparison to baseline, following abrupt treatment discontinuation (for patients with no added RLS therapy after study drug discontinuation).
Assessment of worsening of RLS was based on the IRLS total score assessed 7 ± 1 days after treatment discontinuation (the end of the study or premature discontinuation) compared with that at baseline. Analysis considered the number of patients experiencing a clinically relevant deterioration of ≥4 points in total IRLS score 7 ± 1 days after discontinuation of trial medication compared with baseline.Baseline, Week 26 Mean Supine Systolic Blood Pressure Baseline, Week 26 Baseline, Week 26 Mean Standing Systolic Blood Pressure Baseline, Week 26 Baseline, Week 26 Mean Supine Diastolic Blood Pressure Baseline, Week 26 Baseline, Week 26 Mean Standing Diastolic Blood Pressure Baseline, Week 26 Baseline, Week 26 Mean Standing Pulse Rate Baseline, Week 26 Baseline, Week 26 Mean Supine Pulse Rate Baseline, Week 26
Trial Locations
- Locations (42)
248.629.44003 Boehringer Ingelheim Investigational Site
🇬🇧Chorley, United Kingdom
248.629.3402 Boehringer Ingelheim Investigational Site
🇪🇸Barcelona, Spain
248.629.44004 Boehringer Ingelheim Investigational Site
🇬🇧Glasgow, United Kingdom
248.629.4906 Boehringer Ingelheim Investigational Site
🇩🇪Herborn, Germany
248.629.35303 Boehringer Ingelheim Investigational Site
🇮🇪Co. Tipperary, Ireland
248.629.4904 Boehringer Ingelheim Investigational Site
🇩🇪Berlin (Hellersdorf), Germany
248.629.3405 Boehringer Ingelheim Investigational Site
🇪🇸Granada, Spain
248.629.3403 Boehringer Ingelheim Investigational Site
🇪🇸San Sebastián, Spain
248.629.4304 Boehringer Ingelheim Investigational Site
🇦🇹Linz, Austria
248.629.44001 Boehringer Ingelheim Investigational Site
🇬🇧Manchester, United Kingdom
248.629.4302 Boehringer Ingelheim Investigational Site
🇦🇹Innsbruck, Austria
248.629.35801 Boehringer Ingelheim Investigational Site
🇫🇮Espoo, Finland
248.629.35805 Boehringer Ingelheim Investigational Site
🇫🇮Helsinki, Finland
248.629.35804 Boehringer Ingelheim Investigational Site
🇫🇮Joensuu, Finland
248.629.35802 Boehringer Ingelheim Investigational Site
🇫🇮Oulu, Finland
248.629.4903 Boehringer Ingelheim Investigational Site
🇩🇪Berlin-Steglitz, Germany
248.629.4902 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
248.629.4908 Boehringer Ingelheim Investigational Site
🇩🇪Bochum, Germany
248.629.4901 Boehringer Ingelheim Investigational Site
🇩🇪Ellwangen, Germany
248.629.35301 Boehringer Ingelheim Investigational Site
🇮🇪Carrigtwohill, Ireland
248.629.31001 Boehringer Ingelheim Investigational Site
🇳🇱Bennebroek, Netherlands
248.629.4204 Boehringer Ingelheim Investigational Site
🇸🇰Bratislava, Slovakia
248.629.4202 Boehringer Ingelheim Investigational Site
🇸🇰Brezno, Slovakia
248.629.3401 Boehringer Ingelheim Investigational Site
🇪🇸Madrid, Spain
248.629.3406 Hospital Arnau de Vilanova
🇪🇸Valencia, Spain
248.629.44006 Boehringer Ingelheim Investigational Site
🇬🇧Edgbaston, Birmingham, United Kingdom
248.629.44002 Boehringer Ingelheim Investigational Site
🇬🇧Reading, United Kingdom
248.629.44005 Boehringer Ingelheim Investigational Site
🇬🇧Waterloo, Liverpool, United Kingdom
248.629.4905 Boehringer Ingelheim Investigational Site
🇩🇪Leipzig, Germany
248.629.4909 Boehringer Ingelheim Investigational Site
🇩🇪Schwerin, Germany
248.629.4907 Boehringer Ingelheim Investigational Site
🇩🇪Würzburg, Germany
248.629.31005 Boehringer Ingelheim Investigational Site
🇳🇱Hoogwoud, Netherlands
248.629.31003 Boehringer Ingelheim Investigational Site
🇳🇱Oude Pekela, Netherlands
248.629.4205 Boehringer Ingelheim Investigational Site
🇸🇰Bratislava, Slovakia
248.629.31002 Boehringer Ingelheim Investigational Site
🇳🇱Oude Pekela, Netherlands
248.629.35302 Boehringer Ingelheim Investigational Site
🇮🇪Co. Kildare, Ireland
248.629.4201 Boehringer Ingelheim Investigational Site
🇸🇰Kosice, Slovakia
248.629.4203 Boehringer Ingelheim Investigational Site
🇸🇰Martin, Slovakia
248.629.3201 Boehringer Ingelheim Investigational Site
🇧🇪Edegem, Belgium
248.629.35806 Boehringer Ingelheim Investigational Site
🇫🇮Tampere, Finland
248.629.31006 Boehringer Ingelheim Investigational Site
🇳🇱Musselkanaal, Netherlands
248.629.31004 Boehringer Ingelheim Investigational Site
🇳🇱Rijswijk, Netherlands