Long-term Efficacy, Safety and Tolerability of Pramipexole in Patients With Idiopathic Moderate to Severe Restless Legs Syndrome (RLS)

Restless Legs Syndrome Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00472199
• Other study ID #: 248.629
• Secondary ID: EUDRACT2006-0064
• Status: Completed
• Phase: Phase 4
• First received: May 10, 2007
• Last updated: June 17, 2014
• Start date: May 2007

Study information

• Verified date: May 2012
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Office for Safety in Health CareBelgium: Federal Agency for Medicines and Health Products, FAMHPFinland: Finnish Medicines AgencyGermany: Federal Institute for Drugs and Medical DevicesGreat Britain: MHRAIreland: Irish Medicines BoardNetherlands: Central Committee on Research involving Human Subjects (CCMO)Slovakia: State Institute for Drug ControlSpain: Spanish Agency for Medicines and Health Products
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 331
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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);

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Psychomotor Agitation
• Restless Legs Syndrome
• Syndrome

Intervention

Drug:
• Pramipexole

• Placebo

Locations

Country	Name	City	State
Austria	248.629.4302 Boehringer Ingelheim Investigational Site	Innsbruck
Austria	248.629.4304 Boehringer Ingelheim Investigational Site	Linz
Belgium	248.629.3201 Boehringer Ingelheim Investigational Site	Edegem
Finland	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	248.629.35806 Boehringer Ingelheim Investigational Site	Tampere
Germany	248.629.4902 Boehringer Ingelheim Investigational Site	Berlin
Germany	248.629.4904 Boehringer Ingelheim Investigational Site	Berlin (Hellersdorf)
Germany	248.629.4903 Boehringer Ingelheim Investigational Site	Berlin-Steglitz
Germany	248.629.4908 Boehringer Ingelheim Investigational Site	Bochum
Germany	248.629.4901 Boehringer Ingelheim Investigational Site	Ellwangen
Germany	248.629.4906 Boehringer Ingelheim Investigational Site	Herborn
Germany	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
Ireland	248.629.35301 Boehringer Ingelheim Investigational Site	Carrigtwohill
Ireland	248.629.35302 Boehringer Ingelheim Investigational Site	Co. Kildare
Ireland	248.629.35303 Boehringer Ingelheim Investigational Site	Co. Tipperary
Netherlands	248.629.31001 Boehringer Ingelheim Investigational Site	Bennebroek
Netherlands	248.629.31005 Boehringer Ingelheim Investigational Site	Hoogwoud
Netherlands	248.629.31006 Boehringer Ingelheim Investigational Site	Musselkanaal
Netherlands	248.629.31002 Boehringer Ingelheim Investigational Site	Oude Pekela
Netherlands	248.629.31003 Boehringer Ingelheim Investigational Site	Oude Pekela
Netherlands	248.629.31004 Boehringer Ingelheim Investigational Site	Rijswijk
Slovakia	248.629.4204 Boehringer Ingelheim Investigational Site	Bratislava
Slovakia	248.629.4205 Boehringer Ingelheim Investigational Site	Bratislava
Slovakia	248.629.4202 Boehringer Ingelheim Investigational Site	Brezno
Slovakia	248.629.4201 Boehringer Ingelheim Investigational Site	Kosice
Slovakia	248.629.4203 Boehringer Ingelheim Investigational Site	Martin
Spain	248.629.3402 Boehringer Ingelheim Investigational Site	Barcelona
Spain	248.629.3405 Boehringer Ingelheim Investigational Site	Granada
Spain	248.629.3401 Boehringer Ingelheim Investigational Site	Madrid
Spain	248.629.3403 Boehringer Ingelheim Investigational Site	San Sebastián
Spain	248.629.3406 Hospital Arnau de Vilanova	Valencia
United Kingdom	248.629.44003 Boehringer Ingelheim Investigational Site	Chorley
United Kingdom	248.629.44006 Boehringer Ingelheim Investigational Site	Edgbaston, Birmingham
United Kingdom	248.629.44004 Boehringer Ingelheim Investigational Site	Glasgow
United Kingdom	248.629.44001 Boehringer Ingelheim Investigational Site	Manchester
United Kingdom	248.629.44002 Boehringer Ingelheim Investigational Site	Reading
United Kingdom	248.629.44005 Boehringer Ingelheim Investigational Site	Waterloo, Liverpool

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Austria,  Belgium,  Finland,  Germany,  Ireland,  Netherlands,  Slovakia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in International Restless Legs Syndrome Study Group Rating Scale (IRLS) Total Score After 26 Weeks	IRLS total score ranging from 0 (no RLS symptoms) to 40 (very severe RLS symptoms)	Baseline and 26 weeks	No
Secondary	Clinical Global Impression - Global Improvement (CGI-I) Responder Rate	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)	after 26 weeks of treatment	No
Secondary	International Restless Legs Syndrome (IRLS) Study Group Rating Scale Responder Rate	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)	after 26 weeks of treatment	No
Secondary	Patient Global Impression (PGI) Responder Rate	PGI scores ranging from '1' (very much better) to '7' (very much worse), PGI responder have scoring 1 or 2 (at least much better)	after 26 weeks of treatment	No
Secondary	Change From Baseline in Restless Legs Syndrome-6 (RLS-6) Score "Satisfaction With Sleep" After 26 Weeks	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	baseline and 26 weeks of treatment	No
Secondary	Change From Baseline in RLS-6 Score "Severity Falling Asleep" After 26 Weeks	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	Baseline and 26 weeks of treatment	No
Secondary	Change From Baseline in RLS-6 Score "Severity During the Night" After 26 Weeks	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	baseline and 26 weeks of treatment	No
Secondary	Change From Baseline in RLS-6 Score "Severity During the Day When at Rest" After 26 Weeks	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	Baseline and 26 weeks of treatment	No
Secondary	Change From Baseline RLS-6 Score "Severity During the Day Engaged in Activities" After 26 Weeks	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	Baseline and 26 weeks of treatment	No
Secondary	Change From Baseline in RLS-6 Score "Tired or Sleepy During the Day" After 26 Weeks	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	Baseline and 26 weeks of treatment	No
Secondary	Change From Baseline in IRLS Mood Disturbance Score (Item 10) After 26 Weeks	Mood disturbance associated with RLS symptoms ranging from 0 (none) to 4 (very severe)	Baseline and 26 weeks of treatment	No
Secondary	Change From Baseline in Visual Analogue Scale (VAS) Score for Pain in Limbs After 26 Weeks	The scale measures pain on a continuous 100 mm axis ranging from no pain (0 mm) to unbearable pain (100 mm)	Baseline and 26 weeks of treatment	No
Secondary	Change From Baseline in Quality of Life in RLS (RLS QoL) Score After 26 Weeks	RLS QoL total score ranging from 0 to 100 with higher values indicating better quality of life	Baseline and 26 weeks of treatment	No
Secondary	Change From Baseline in Short Form-36 (SF-36) Dimension Bodily Pain After 26 Weeks	Score ranging from 0 to 100 with higher scores indicating less bodily pain	Baseline and 26 weeks	No
Secondary	Change From Baseline in SF-36 Dimension General Health After 26 Weeks	Score ranging from 0 to 100 with higher scores indicating better health status	Baseline and 26 weeks	No
Secondary	Change From Baseline in SF-36 Dimension Mental Health After 26 Weeks	Score ranging from 0 to 100 with higher scores indicating better mental health	Baseline and 26 weeks	No
Secondary	Change From Baseline in SF-36 Dimension Physical Functioning After 26 Weeks	Score ranging from 0 to 100 with higher scores indicating better physical functioning	Baseline and 26 weeks	No
Secondary	Change From Baseline in SF-36 Dimension Role Limitations Due to Emotional Problems After 26 Weeks	Score ranging from 0 to 100 with higher scores indicating less limitations due to emotional problems	Baseline and 26 weeks	No
Secondary	Change From Baseline in SF-36 Dimension Role Limitations Due to Physical Problems After 26 Weeks	Score ranging from 0 to 100 with higher scores indicating less limitations due to physical problems	Baseline and 26 weeks	No
Secondary	Change From Baseline in SF-36 Dimension Social Functioning After 26 Weeks	Score ranging from 0 to 100 with higher scores indicating better social functioning	Baseline and 26 weeks	No
Secondary	Change From Baseline in SF-36 Dimension Vitality After 26 Weeks	Score ranging from 0 to 100 with higher scores indicating better vitality	Baseline and 26 weeks	No
Secondary	Change From Baseline in SF-36 Dimension Mental Component Summary After 26 Weeks	Score ranging from 0 to 100 with higher scores indicating better health	Baseline and 26 weeks	No
Secondary	Change From Baseline in SF-36 Dimension Physical Component Summary After 26 Weeks	Score ranging from 0 to 100 with higher scores indicating better health	Baseline and 26 weeks	No
Secondary	Diagnosis of Classified Augmentation According to Independent Expert Panel	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.	after at least 4 weeks of treatment	No
Secondary	Worsening of RLS Symptoms (by at Least 4 Points in the IRLS Total Score Compared to Baseline) After 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.	after at least 1 week of treatment discontinuation	No
Secondary	Baseline, Week 26 Mean Supine Systolic Blood Pressure		Baseline, Week 26	No
Secondary	Baseline, Week 26 Mean Standing Systolic Blood Pressure		Baseline, Week 26	No
Secondary	Baseline, Week 26 Mean Supine Diastolic Blood Pressure		Baseline, Week 26	No
Secondary	Baseline, Week 26 Mean Standing Diastolic Blood Pressure		Baseline, Week 26	No
Secondary	Baseline, Week 26 Mean Supine Pulse Rate		Baseline, Week 26	No
Secondary	Baseline, Week 26 Mean Standing Pulse Rate		Baseline, Week 26	No

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