Long-term Study Of Ropinirole In Restless Legs Syndrome

NCT00329602 | Completed Phase 4 Results

• 1 other identifier: ROR104836
• Study Type: interventional
• Target: 404
• Locations: 11 countries
• Sites: 39

Brief 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.

Conditions

Restless Legs Syndrome

Keywords

Moderate; Restless Legs Syndrome; Severe; ropinirole

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline and Weeks 12 and 26

• 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.

  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)

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

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

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

  Baseline and Weeks 12 and 26

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

  Baseline and Weeks 12 and 26

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

  Baseline and Weeks 12 and 26

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

  Baseline and Weeks 12 and 26

Study Arms (2)

Double-blind for 12 to 26 Weeks

PLACEBO COMPARATOR

Double-blind (Ropinirole:Placebo) for 12 to 26 weeks

Drug: Placebo; Drug: Ropinirole

Open-label ropinirole for 40-Weeks

OTHER

Open label ropinirole for 40 weeks

Drug: Ropinirole

Interventions

Placebo DRUG

Matching Placebo

Double-blind for 12 to 26 Weeks

Ropinirole DRUG

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

Double-blind for 12 to 26 Weeks; Open-label ropinirole for 40-Weeks

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (39)

GSK Investigational Site

Camperdown, New South Wales, 2050, Australia

Location

GSK Investigational Site

Kippa-Ring, Queensland, 4021, Australia

Location

GSK Investigational Site

Woodville, South Australia, 5011, Australia

Location

GSK Investigational Site

Clayton, Victoria, 3168, Australia

Location

GSK Investigational Site

East Melbourne, Victoria, 3002, Australia

Location

GSK Investigational Site

Olomouc, 775 20, Czechia

Location

GSK Investigational Site

Ostrava, 702 00, Czechia

Location

GSK Investigational Site

Pardubice, 535 03, Czechia

Location

GSK Investigational Site

Prague, 120 00, Czechia

Location

GSK Investigational Site

Aalborg, 9000, Denmark

Location

GSK Investigational Site

Odense C, 5000, Denmark

Location

GSK Investigational Site

Vejle, 7100, Denmark

Location

GSK Investigational Site

Bamberg, Bavaria, 96047, Germany

Location

GSK Investigational Site

Munich, Bavaria, 80331, Germany

Location

GSK Investigational Site

Regensburg, Bavaria, 93053, Germany

Location

GSK Investigational Site

Marburg, Hesse, 35039, Germany

Location

GSK Investigational Site

Westerstede, Lower Saxony, 26655, Germany

Location

GSK Investigational Site

Schwerin, Mecklenburg-Vorpommern, 19053, Germany

Location

GSK Investigational Site

Berlin, State of Berlin, 10787, Germany

Location

GSK Investigational Site

Berlin, State of Berlin, 10969, Germany

Location

GSK Investigational Site

Bologna, Emilia-Romagna, 40123, Italy

Location

GSK Investigational Site

Rome, Lazio, 00163, Italy

Location

GSK Investigational Site

Pavia, Lombardy, 27100, Italy

Location

GSK Investigational Site

Hamar, 2317, Norway

Location

GSK Investigational Site

Coimbra, 3000-075, Portugal

Location

GSK Investigational Site

Lisbon, 1649-035, Portugal

Location

GSK Investigational Site

Bratislava, 831 03, Slovakia

Location

GSK Investigational Site

Bratislava, 833 05, Slovakia

Location

GSK Investigational Site

Dubnica nad Váhom, 018 41, Slovakia

Location

GSK Investigational Site

Levoča, 054 01, Slovakia

Location

GSK Investigational Site

Žilina, 010 01, Slovakia

Location

GSK Investigational Site

Barcelona, 08017, Spain

Location

GSK Investigational Site

Madrid, 28036, Spain

Location

GSK Investigational Site

San Sebastián, 20014, Spain

Location

GSK Investigational Site

Avesta, SE-774 82, Sweden

Location

GSK Investigational Site

Gothenburg, SE-412 55, Sweden

Location

GSK Investigational Site

Örebro, 701 85, Sweden

Location

GSK Investigational Site

Bern, 3010, Switzerland

Location

GSK Investigational Site

Zurich, 8091, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 22328464 BACKGROUND

• 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.

  PMID: 23938061 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Restless Legs Syndrome; Lymphoma, Follicular

Interventions

ropinirole

Condition Hierarchy (Ancestors)

Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Parasomnias; Mental Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2006
• First Posted: May 25, 2006
• Study Start: March 1, 2006
• Primary Completion: September 1, 2008
• Study Completion: September 1, 2008
• Last Updated: March 23, 2017
• Results First Posted: May 27, 2010

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will share

Locations

SL (5); DE (8); DK (3); PT (2); AU (5); SE (3); CH (2); NO (1); IT (3); ES (3); CZ (4)