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Restless Legs SyndromePhase 4NCT00329602

Long-term Study Of Ropinirole In Restless Legs Syndrome

A Phase 4 study testing Ropinirole in people with Restless Legs Syndrome, run by GlaxoSmithKline at 39 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is an initial placebo-controlled study followed by open treatment evaluating the effectiveness and tolerability of ropinirole long-term in patients with moderate to severe Restless Legs Syndrome. Read more about this study

Who is it for?
Ages 18 to 79 years
Conditions the study is for
Restless Legs Syndrome
What is being tested?
Ropinirole
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
404 participants
Where
39 sitesin 11 countries
Study dates
Mar 2006to Sep 2008
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 79 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male and female subjects, between the ages of 18 and 79, inclusive
  • A female is eligible to enter and participate in the study if she is of:
  • Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or,
  • Childbearing potential, has a negative result on all required pregnancy tests prior to randomisation, and agrees to an acceptable contraceptive method.
  • Subjects with a diagnosis of idiopathic RLS using the RLS Diagnostic Clinical Interview and the International RLS Study Group (IRLSSG) Diagnostic Criteria during the Screening Visit.
  • Subjects have had RLS symptoms with a history of a minimum of 15 RLS episodes during the previous month. If this is not possible due to the subject being on previous medication to treat RLS the investigator should ensure that the subject should have experienced 4-5 episodes of RLS symptoms during the last 7 days of the wash-out phase (see below). The subject must discontinue and wash-out any previous medication for the treatment of RLS or sleep prior to the Baseline Visit (Day 0). The minimum discontinuation period for wash-out is generally 5 half-lives of the medication or 7 consecutive evenings/nights medication-free prior to baseline, whichever is the longer period.
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  • During the Wash-out and Screening Phase, RLS symptoms must be present for at least 4 of the last 7 nights immediately prior to the Baseline Visit (e.g., any combination of evenings and /or nights for = 4 days).
  • Subjects with a total score = 24 on the IRLS Rating Scale at baseline (Day 0).
  • Subjects with RLS symptoms that cause significant sleep impairment based on clinical judgment and guided by subject response to Question 4 of the IRLS Rating Scale (e.g., ordinarily this will include a response of (3) severe or (4) very severe sleep disturbance) at the Baseline Visit OR RLS symptoms that cause severe/very severe discomfort in the limbs based on clinical judgment and guided by subject response to Question 1 of the IRLS Rating Scale (e.g., this will include a response of (3) severe or (4) very severe discomfort in limbs) at the Baseline Visit (Day 0).
  • Subjects must be experiencing RLS symptoms requiring treatment at night-time.
  • Subjects must have given written informed consent prior to any specific study procedures.

Who cannot join

  • Subjects suffering from augmentation and/ or 'end of treatment' rebound RLS symptoms at baseline (Day 0). Augmentation is defined as RLS symptoms that occurred while on treatment and occur earlier in the afternoon/evening than they did before, symptoms which are more severe than when not treated, symptoms which start after less time at rest than they did before treatment, or symptoms which involve other parts of the body, such as the arms or trunk. 'End of treatment' rebound describes worsening of symptoms from baseline that occur after pharmacological treatment is stopped.
  • Subjects with a previous history of augmentation.
  • Subjects who have exhibited intolerance to ropinirole or any other dopamine agonist.
  • Subjects requiring treatment of daytime RLS symptoms (daytime defined as 10:00 hours until 17:00 hours).
  • Signs of secondary RLS (e.g., end stage renal disease, iron deficient anaemia or pregnancy at Baseline Visit).
  • Subjects with a serum ferritin level of < 10 mcg/L (ng/mL) at Screening Visit.
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  • Subjects who suffer from a primary sleep disorder other than RLS that may significantly affect the symptoms of RLS (e.g. narcolepsy, sleep terror disorder, sleepwalking disorder, breathing related sleep disorder).
  • Subjects diagnosed with movement disorders (e.g., Parkinson's Disease, dyskinesias, and dystonias).
  • Subjects who have medical conditions which could affect efficacy assessments or clinically significant or unstable medical conditions that present a safety concern. These may include, but are not limited to, the following disorders: diabetes, peripheral neuropathy, rheumatoid arthritis, fibromyalgia syndrome, symptomatic orthostatic hypotension, severe cardiovascular disease, hepatic or renal failure, pleuro-pulmonary fibrosis, major psychotic illness.
  • Subjects having a clinically significant abnormal laboratory value, ECG, or physical examination findings not resolved by the time of the baseline examinations (Day 0). Abnormal 12-lead ECG findings include, but are not limited to, the following: myocardial ischemia, clinically significant conduction abnormalities, or clinically significant arrhythmias.
  • Subjects with a diastolic blood pressure = 110mmHg or = 50mmHg or systolic blood pressure = 180mmHg or = 90mmHg at the Screening or Baseline Visit.
  • Subjects with a history of alcohol or substance abuse within the past year.
  • Subjects taking any medication known to induce drowsiness, affect RLS or sleep and which have not been discontinued prior to the Baseline Visit. These medications include the following:
  • Atypical and typical antipsychotics, anticonvulsants, opioids (including propoxyphene and oxycodone), anxiolytics, all sedatives/hypnotics (including benzodiazepines), lithium, oral neuroleptics, stimulants (including methylphenidate), dopamine agonists (including ropinirole), dopamine antagonists (e.g., typical neuroleptics, metoclopramide), levodopa/carbidopa, clonidine, and sedating antihistamines (e.g., chlorpheniramine, diphenhydramine, hydroxyzine) or any preparations containing these antihistamines.
  • The minimum discontinuation period is generally 5 half lives or 7 consecutive evenings/nights medication free, prior to baseline, whichever is the longer period. Exceptions to this general rule are: fluoxetine, monoamine oxidase inhibitors: 4 weeks.
  • For subjects entering the 40-week, open-label treatment phase, the GSK Medical Monitor can be contacted to discuss individual cases where adherence to the above may not have occurred.
  • Withdrawal, introduction, or change in dose of hormone replacement therapy (HRT) and/or any drug known to substantially inhibit CYP1A2 (e.g., ciprofloxacin, cimetidine, fluvoxamine, HRT) or induce CYP1A2 (e.g., tobacco, omeprazole) within 7 days prior to enrolment. Subjects already on these agents may be enrolled, but must remain on stable doses of the agents from 7 days prior to enrolment through to the follow-up visit at the end of the study.
  • Night workers or any others whose sleeping habits are incompatible with the study design, or who would be required to make significant changes to their bedtime during the course of the study.
  • Participation in any clinical drug or device trial in the one month prior to the Baseline Visit.
  • Subjects who, in the opinion of the investigator, would be non-compliant with the visit schedules or other study procedures.
  • Women who have a positive pregnancy test or who are lactating.

Trial locations and contacts

39 sites in 11 countries.

39 sites in 11 countries

Germany8 sites

  • GSK Investigational Site

    Bamberg, Bavaria, 96047

  • GSK Investigational Site

    Berlin, State of Berlin, 10787

  • GSK Investigational Site

    Berlin, State of Berlin, 10969

  • GSK Investigational Site

    Marburg, Hesse, 35039

  • GSK Investigational Site

    Munich, Bavaria, 80331

  • GSK Investigational Site

    Regensburg, Bavaria, 93053

  • GSK Investigational Site

    Schwerin, Mecklenburg-Vorpommern, 19053

  • GSK Investigational Site

    Westerstede, Lower Saxony, 26655

Other trials in Germany

Australia5 sites

  • GSK Investigational Site

    Camperdown, New South Wales, 2050

  • GSK Investigational Site

    Clayton, Victoria, 3168

  • GSK Investigational Site

    East Melbourne, Victoria, 3002

  • GSK Investigational Site

    Kippa-Ring, Queensland, 4021

  • GSK Investigational Site

    Woodville, South Australia, 5011

Other trials in Australia

Slovakia5 sites

  • GSK Investigational Site

    Bratislava, 831 03

  • GSK Investigational Site

    Bratislava, 833 05

  • GSK Investigational Site

    Dubnica nad Váhom, 018 41

  • GSK Investigational Site

    Levoča, 054 01

  • GSK Investigational Site

    Žilina, 010 01

Other trials in Slovakia

Czechia4 sites

  • GSK Investigational Site

    Olomouc, 775 20

  • GSK Investigational Site

    Ostrava, 702 00

  • GSK Investigational Site

    Pardubice, 535 03

  • GSK Investigational Site

    Prague, 120 00

Other trials in Czechia

Denmark3 sites

  • GSK Investigational Site

    Aalborg, 9000

  • GSK Investigational Site

    Odense C, 5000

  • GSK Investigational Site

    Vejle, 7100

Other trials in Denmark

Italy3 sites

  • GSK Investigational Site

    Bologna, Emilia-Romagna, 40123

  • GSK Investigational Site

    Pavia, Lombardy, 27100

  • GSK Investigational Site

    Rome, Lazio, 00163

Other trials in Italy

Spain3 sites

  • GSK Investigational Site

    Barcelona, 08017

  • GSK Investigational Site

    Madrid, 28036

  • GSK Investigational Site

    San Sebastián, 20014

Other trials in Spain

Sweden3 sites

  • GSK Investigational Site

    Avesta, SE-774 82

  • GSK Investigational Site

    Gothenburg, SE-412 55

  • GSK Investigational Site

    Örebro, 701 85

Other trials in Sweden

Portugal2 sites

  • GSK Investigational Site

    Coimbra, 3000-075

  • GSK Investigational Site

    Lisbon, 1649-035

Other trials in Portugal

Switzerland2 sites

  • GSK Investigational Site

    Bern, 3010

  • GSK Investigational Site

    Zurich, 8091

Other trials in Switzerland

Norway1 site

  • GSK Investigational Site

    Hamar, 2317

Other trials in Norway

About this study

Official title: A Parallel Group Study to Evaluate the Efficacy and Safety of Ropinirole for 26 Weeks and to Further Evaluate the Incidence of Augmentation and Rebound for a Further 40 Weeks Open-label Extension Treatment Period in Subjects Suffering From Moderate to Severe Restless Legs Syndrome.

This is an initial placebo-controlled study followed by open treatment evaluating the effectiveness and tolerability of ropinirole long-term in patients with moderate to severe Restless Legs Syndrome.

Read the detailed description

A randomised, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of ropinirole for 26 weeks and to further evaluate the incidence of augmentation and rebound for a further 40 weeks open-label extension treatment period in subjects suffering from moderate to severe Restless Legs Syndrome.

Being tested
Placebo, Ropinirole
Keywords
Moderate, Restless Legs Syndrome, Severe, ropinirole
Medical subject headings
Restless Legs Syndrome, Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboDrug

    Matching Placebo

  • RopiniroleDrug

    Ropinirole IR 0.25mg/day to 4mg/day for RLS

Study groups in NCT00329602
Study groupRoleWhat they receive
Double-blind for 12 to 26 WeeksPlacebo comparatorDouble-blind (Ropinirole:Placebo) for 12 to 26 weeks
Receives: Drug: Placebo; Drug: Ropinirole
Open-label ropinirole for 40-WeeksOtherOpen label ropinirole for 40 weeks
Receives: Drug: Ropinirole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26

    A 10-item, participant-reported scale covering different symptoms of the condition. Each item is scored from 0 to 4; 0 represents the absence of a problem and 4 reflects a very severe problem. The best and worst possible scores are 0 and 40, respectively; higher scores represent a greater severity of symptoms. A negative change from baseline indicates improvement, and a negative treatment difference indicates a benefit of Ropinirole IR over placebo. The primary assessment was made by calculating the difference in the average score obtained at Baseline with scores at Week 12 and then Week 26.

    Measured: Baseline and Weeks 12 and 26

  2. Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases

    Clinically meaningful augmentation and early morning rebound (EMR) were assessed and confirmed by an independent Adjudication Board. EMR describes the development of RLS symptoms during the early morning, following therapeutic intervention. EMR is differentiated from augmentation, in which the earlier onset of symptoms occurs in the evening.

    Measured: During 15-month study duration at scheduled (Weeks 16, 20, 26, or early withdrawal for DB phase; Weeks 39, 47, 55, 63, 67, or early withdrawal for the OL phase) and unscheduled (26-week DB phase and 40-week OL phase) visits

Secondary outcomes (11)

  1. Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at Weeks 1, 4, 8, 16, and 20

    A 10-item, participant-reported scale covering different RLS symptoms. Each item is scored from 0 to 4; 0 represents the absence of a problem and 4 reflects a very severe problem. The best and worst possible scores are 0 and 40, respectively; higher scores represent a greater severity of symptoms. The primary assessment from this study was made by calculating the difference in the average score obtained at Baseline with scores at Weeks 1, 4, 8, 16, and 20. Scores were adjusted for baseline IRLS total score, treatment group, visit, visit by treatment group interaction, and center group.

    Measured: Baseline and Weeks 1, 4, 8, 16, and 20

  2. Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26

    The MOS-12 Sleep Scale is a comprehensive battery, which measures specific aspects of sleep in participants that may have varying co-morbidities, and, as a result, is appropriate for a medically diverse participant population. Domain values are presented on a 0-100 scale, where a higher score means a greater degree of the attribute implied by the scale name. Scores were adjusted for baseline MOS sleep scale domain value, treatment group, visit, visit by treatment interaction, and center group.

    Measured: Baseline and Weeks 12 and 26

  3. Change From Baseline in Sleep Quantity, a Domain of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale, at Weeks 12 and 26

    The MOS-12 Sleep Scale is a comprehensive battery, which measures specific aspects of sleep in participants that may have varying co-morbidities, and, as a result, is appropriate for a medically diverse participant population.Scores were adjusted for baseline MOS sleep scale domain value, treatment group, visit, visit by treatment interaction, and center group.

    Measured: Baseline and Weeks 12 and 26

  4. Change From Baseline in the Johns Hopkins RLS Quality of Life (RLS QoL) Questionnaire Overall Life Impact Score at Weeks 12 and 26

    The Johns Hopkins RLS QoL Questionnaire is a disease-specific instrument that assesses the impact of RLS on the daily life, emotional well-being, social life, and work life of participants. The overall life impact score for the John Hopkins RLS QoL scale ranges from a lowest possible score of 0 to a highest possible score of 100. Higher scores represent better quality of life. Scores were adjusted for baseline RLS Quality of Life score, treatment group, visit, visit by treatment interaction, and center group.

    Measured: Baseline and Weeks 12 and 26

  5. Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26

    The MOS SF-36 is a generic QoL instrument measuring functional status and well-being. Positive change from baseline for all domains indicates improvement. For all MOS SF-36 domains, the minimum and maximum scores are 0 and 100, respectively, for the transformed scale. Scores were adjusted for baseline domain score, treatment group, visit, visit by treatment interaction, and center group.

    Measured: Baseline and Weeks 12 and 26

  6. Percentage of Participants With a Score of Much/Very Much Improved on the Clinical Global Impression-Global Improvement (CGI-I) Scale at Weeks 1, 12 and 26

    The CGI-I is a psychometric instrument that is used to measure general clinical status in a variety of disease states. The CGI-I allows the investigator to rate the participant's global improvement or worsening compared with the condition at Baseline (Day 0). The scale is rated from 1-7 (1 = very much improved; 7 = very much worse). Typically, a participant with a score of 1 or 2 (much improved) is considered a responder.

    Measured: Weeks 1, 12 and 26

  7. Number of Participants Withdrawing Due to Lack of Efficacy During the First 26 Weeks of the Study

    Lack of efficacy is defined as up to a 10% improvement in the IRLS Rating Scale total score from the participant's Baseline value and at least 12 weeks of treatment during the double-blind phase.

    Measured: Baseline to Week 26

  8. Number of Participants Rated as Normal or Borderline Ill on the CGI Severity of Illness (CGI-S) Scale at Week 26

    The CGI-S scale is a psychometric instrument that is used to measure general clinical status in a variety of disease states. The CGI-S allows the investigator to rate the severity of the participant's illness considering their total clinical experience with the subject population being studied and on all information available at the time of rating. The scale is rated from 1-7 (1 = normal, not at all ill; 2 = borderline ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severly ill; 7 = among the most extremely ill participants).

    Measured: Week 26

  9. Median Time to First CGI-I Response of Much/Very Much Improved During the Double-blind Phase

    The median time to first CGI-I response of much/very much improved was calculated. The CGI-I is a psychometric instrument that is used to measure general clinical status in a variety of disease states. The CGI-I allows the investigator to rate the participant's global improvement or worsening compared with the condition at Baseline (Day 0). The scale is rated from 1-7 (1 = very much improved; 7 = very much worse). Typically, a participant with a score of 1 or 2 (much improved) is considered a responder.

    Measured: Baseline to Week 26

  10. Number of Participants With a Score of Much/Very Much Improved on the CGI-I Scale at Week 67

    The CGI-I is a psychometric instrument that is used to measure general clinical status in a variety of disease states. The CGI-I allows the investigator to rate the participant's global improvement or worsening compared with the condition at Baseline (Day 0). The scale is rated from 1-7 (1 = very much improved; 7 = very much worse). Typically, a participant with a score of 1 or 2 (much improved) is considered a responder.

    Measured: Week 67

  11. Mean Change From Baseline in the IRLS Rating Scale Total Score at Week 67

    A 10-item, participant-reported scale covering different symptoms of the condition. Each item is scored from 0 to 4, with 0 representing the absence of a problem and 4 reflecting a very severe problem. The best and worst possible scores are 0 and 40, respectively. The primary assessment was made by calculating the difference in the average score obtained at Baseline with score at Week 67.

    Measured: Baseline and Week 67

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 May 2006 (estimated)
  2. Study startMar 2006
  3. Primary completionSep 2008
  4. Study completionSep 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
404 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00329602
Sponsor's protocol ID
ROR104836
Status last verified
Mar 2017
First submitted
23 May 2006
Last updated
23 Mar 2017
Data monitoring committee
No
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

  • Garcia-Borreguero D, Hogl B, Ferini-Strambi L, Winkelman J, Hill-Zabala C, Asgharian A, Allen R. Systematic evaluation of augmentation during treatment with ropinirole in restless legs syndrome (Willis-Ekbom disease): results from a prospective, multicenter study over 66 weeks. Mov Disord. 2012 Feb;27(2):277-83. doi: 10.1002/mds.24889. Epub 2012 Jan 4.

    PubMed 22328464

  • Giorgi L, Asgharian A, Hunter B. Ropinirole in patients with restless legs syndrome and baseline IRLS total scores >/= 24: efficacy and tolerability in a 26-week, double-blind, parallel-group, placebo-controlled study followed by a 40-week open-label extension. Clin Ther. 2013 Sep;35(9):1321-36. doi: 10.1016/j.clinthera.2013.06.016. Epub 2013 Aug 9.

    PubMed 23938061

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Ropinirole in people with Restless Legs Syndrome, run by GlaxoSmithKline at 39 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 39 sites in Germany, Australia, Slovakia, Czechia, Denmark and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 May 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26 (time frame: Baseline and Weeks 12 and 26). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00329602, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2017.

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