Clinical trial NCT00472199: Long-term Efficacy, Safety and Tolerability of Pramipexole in Patients With Idiopathic Moderate to Severe Restless Legs Syndrome (RLS)
Official title: A Phase IV Randomised, Double-blind, Placebo-controlled, Dose Titration Trial With Pramipexole (Sifrol, Mirapexin) 0.125-0.75 mg/Day Per os to Investigate the Long-term Efficacy, Safety and Tolerability in Patients With Idiopathic Moderate to Severe Restless Legs Syndrome for 26 Weeks Followed by a 26 Week Open-label Extension Treatment Period
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Restless Legs Syndrome
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2007-05-11
Enrollment: 331
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. 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
2. Male or female out-patients aged 18-85 years
3. 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.
4. RLS symptoms present at least 2 to 3 days per week during the last 3 months prior to baseline (Visit 2)
5. IRLS total score \>15 at baseline (Visit 2)

Exclusion Criteria:

1. 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
2. Any woman of child-bearing potential not having a negative pregnancy test at screening
3. Breastfeeding women
4. Patients with known hypersensitivity to pramipexole or any other component of the investigational product or placebo tablets
5. Diagnosis of augmentation under previous pharmacological RLS treatment
6. 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);

Primary outcomes:
measure: Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Total Score After 26 Weeks
timeFrame: Baseline and 26 weeks
Secondary outcomes:
measure: Clinical Global Impression - Global Improvement (CGI-I) Responder Rate
timeFrame: after 26 weeks of treatment
measure: International Restless Legs Syndrome (IRLS) Study Group Rating Scale Responder Rate
timeFrame: after 26 weeks of treatment
measure: Patient Global Impression (PGI) Responder Rate
timeFrame: after 26 weeks of treatment
measure: Change From Baseline in Restless Legs Syndrome-6 (RLS-6) Score "Satisfaction With Sleep" After 26 Weeks
timeFrame: baseline and 26 weeks of treatment
measure: Change From Baseline in RLS-6 Score "Severity Falling Asleep" After 26 Weeks
timeFrame: Baseline and 26 weeks of treatment
measure: Change From Baseline in RLS-6 Score "Severity During the Night" After 26 Weeks
timeFrame: baseline and 26 weeks of treatment
measure: Change From Baseline in RLS-6 Score "Severity During the Day When at Rest" After 26 Weeks
timeFrame: Baseline and 26 weeks of treatment
measure: Change From Baseline RLS-6 Score "Severity During the Day Engaged in Activities" After 26 Weeks
timeFrame: Baseline and 26 weeks of treatment
measure: Change From Baseline in RLS-6 Score "Tired or Sleepy During the Day" After 26 Weeks
timeFrame: Baseline and 26 weeks of treatment
measure: Change From Baseline in IRLS Mood Disturbance Score (Item 10) After 26 Weeks
timeFrame: Baseline and 26 weeks of treatment
measure: Change From Baseline in Visual Analogue Scale (VAS) Score for Pain in Limbs After 26 Weeks
timeFrame: Baseline and 26 weeks of treatment
measure: Change From Baseline in Quality of Life in RLS (RLS QoL) Score After 26 Weeks
timeFrame: Baseline and 26 weeks of treatment
measure: Change From Baseline in Short Form-36 (SF-36) Dimension Bodily Pain After 26 Weeks
timeFrame: Baseline and 26 weeks
measure: Change From Baseline in SF-36 Dimension General Health After 26 Weeks
timeFrame: Baseline and 26 weeks
measure: Change From Baseline in SF-36 Dimension Mental Health After 26 Weeks
timeFrame: Baseline and 26 weeks
measure: Change From Baseline in SF-36 Dimension Physical Functioning After 26 Weeks
timeFrame: Baseline and 26 weeks
measure: Change From Baseline in SF-36 Dimension Role Limitations Due to Emotional Problems After 26 Weeks
timeFrame: Baseline and 26 weeks
measure: Change From Baseline in SF-36 Dimension Role Limitations Due to Physical Problems After 26 Weeks
timeFrame: Baseline and 26 weeks
measure: Change From Baseline in SF-36 Dimension Social Functioning After 26 Weeks
timeFrame: Baseline and 26 weeks
measure: Change From Baseline in SF-36 Dimension Vitality After 26 Weeks
timeFrame: Baseline and 26 weeks
measure: Change From Baseline in SF-36 Dimension Mental Component Summary After 26 Weeks
timeFrame: Baseline and 26 weeks
measure: Change From Baseline in SF-36 Dimension Physical Component Summary After 26 Weeks
timeFrame: Baseline and 26 weeks
measure: Diagnosis of Classified Augmentation According to Independent Expert Panel
timeFrame: after at least 4 weeks of treatment
measure: Worsening of RLS Symptoms (by at Least 4 Points in the IRLS Total Score Compared to Baseline) After Treatment Discontinuation
timeFrame: after at least 1 week of treatment discontinuation
measure: Baseline, Week 26 Mean Supine Systolic Blood Pressure
timeFrame: Baseline, Week 26
measure: Baseline, Week 26 Mean Standing Systolic Blood Pressure
timeFrame: Baseline, Week 26
measure: Baseline, Week 26 Mean Supine Diastolic Blood Pressure
timeFrame: Baseline, Week 26
measure: Baseline, Week 26 Mean Standing Diastolic Blood Pressure
timeFrame: Baseline, Week 26
measure: Baseline, Week 26 Mean Supine Pulse Rate
timeFrame: Baseline, Week 26
measure: Baseline, Week 26 Mean Standing Pulse Rate
timeFrame: Baseline, Week 26
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: 248.629.4302 Boehringer Ingelheim Investigational Site
city: Linz
country: Austria
facility: 248.629.4304 Boehringer Ingelheim Investigational Site
city: Edegem
country: Belgium
facility: 248.629.3201 Boehringer Ingelheim Investigational Site
city: Espoo
country: Finland
facility: 248.629.35801 Boehringer Ingelheim Investigational Site
city: Helsinki
country: Finland
facility: 248.629.35805 Boehringer Ingelheim Investigational Site
city: Joensuu
country: Finland
facility: 248.629.35804 Boehringer Ingelheim Investigational Site
city: Oulu
country: Finland
facility: 248.629.35802 Boehringer Ingelheim Investigational Site
city: Tampere
country: Finland
facility: 248.629.35806 Boehringer Ingelheim Investigational Site
city: Berlin (Hellersdorf)
country: Germany
facility: 248.629.4904 Boehringer Ingelheim Investigational Site
city: Berlin-Steglitz
country: Germany
facility: 248.629.4903 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 248.629.4902 Boehringer Ingelheim Investigational Site
city: Bochum
country: Germany
facility: 248.629.4908 Boehringer Ingelheim Investigational Site
city: Ellwangen
country: Germany
facility: 248.629.4901 Boehringer Ingelheim Investigational Site
city: Herborn
country: Germany
facility: 248.629.4906 Boehringer Ingelheim Investigational Site
city: Leipzig
country: Germany
facility: 248.629.4905 Boehringer Ingelheim Investigational Site
city: Schwerin
country: Germany
facility: 248.629.4909 Boehringer Ingelheim Investigational Site
city: Würzburg
country: Germany
facility: 248.629.4907 Boehringer Ingelheim Investigational Site
city: Carrigtwohill
country: Ireland
facility: 248.629.35301 Boehringer Ingelheim Investigational Site
city: Co. Kildare
country: Ireland
facility: 248.629.35302 Boehringer Ingelheim Investigational Site
city: Co. Tipperary
country: Ireland
facility: 248.629.35303 Boehringer Ingelheim Investigational Site
city: Bennebroek
country: Netherlands
facility: 248.629.31001 Boehringer Ingelheim Investigational Site
city: Hoogwoud
country: Netherlands
facility: 248.629.31005 Boehringer Ingelheim Investigational Site
city: Musselkanaal
country: Netherlands
facility: 248.629.31006 Boehringer Ingelheim Investigational Site
city: Oude Pekela
country: Netherlands
facility: 248.629.31002 Boehringer Ingelheim Investigational Site
city: Oude Pekela
country: Netherlands
facility: 248.629.31003 Boehringer Ingelheim Investigational Site
city: Rijswijk
country: Netherlands
facility: 248.629.31004 Boehringer Ingelheim Investigational Site
city: Bratislava
country: Slovakia
facility: 248.629.4204 Boehringer Ingelheim Investigational Site
city: Bratislava
country: Slovakia
facility: 248.629.4205 Boehringer Ingelheim Investigational Site
city: Brezno
country: Slovakia
facility: 248.629.4202 Boehringer Ingelheim Investigational Site
city: Kosice
country: Slovakia
facility: 248.629.4201 Boehringer Ingelheim Investigational Site
city: Martin
country: Slovakia
facility: 248.629.4203 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 248.629.3402 Boehringer Ingelheim Investigational Site
city: Granada
country: Spain
facility: 248.629.3405 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 248.629.3401 Boehringer Ingelheim Investigational Site
city: San Sebastián
country: Spain
facility: 248.629.3403 Boehringer Ingelheim Investigational Site
city: Valencia
country: Spain
facility: 248.629.3406 Hospital Arnau de Vilanova
city: Chorley
country: United Kingdom
facility: 248.629.44003 Boehringer Ingelheim Investigational Site
city: Edgbaston, Birmingham
country: United Kingdom
facility: 248.629.44006 Boehringer Ingelheim Investigational Site
city: Glasgow
country: United Kingdom
facility: 248.629.44004 Boehringer Ingelheim Investigational Site
city: Manchester
country: United Kingdom
facility: 248.629.44001 Boehringer Ingelheim Investigational Site
city: Reading
country: United Kingdom
facility: 248.629.44002 Boehringer Ingelheim Investigational Site
city: Waterloo, Liverpool
country: United Kingdom
facility: 248.629.44005 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: