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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00329602




Registration number
NCT00329602
Ethics application status
Date submitted
23/05/2006
Date registered
25/05/2006
Date last updated
23/03/2017

Titles & IDs
Public title
Long-term Study Of Ropinirole In Restless Legs Syndrome
Scientific 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.
Secondary ID [1] 0 0
ROR104836
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Restless Legs Syndrome 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Anxiety
Mental Health 0 0 0 0
Other mental health disorders
Neurological 0 0 0 0
Other neurological disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - Ropinirole

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

Other: Open-label ropinirole for 40-Weeks - Open label ropinirole for 40 weeks


Treatment: Drugs: Placebo
Matching Placebo

Treatment: Drugs: Ropinirole
Ropinirole IR 0.25mg/day to 4mg/day for RLS
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26
Timepoint [1] 0 0
Baseline and Weeks 12 and 26
Primary outcome [2] 0 0
Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases
Timepoint [2] 0 0
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 outcome [1] 0 0
Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at Weeks 1, 4, 8, 16, and 20
Timepoint [1] 0 0
Baseline and Weeks 1, 4, 8, 16, and 20
Secondary outcome [2] 0 0
Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26
Timepoint [2] 0 0
Baseline and Weeks 12 and 26
Secondary outcome [3] 0 0
Change From Baseline in Sleep Quantity, a Domain of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale, at Weeks 12 and 26
Timepoint [3] 0 0
Baseline and Weeks 12 and 26
Secondary outcome [4] 0 0
Change From Baseline in the Johns Hopkins RLS Quality of Life (RLS QoL) Questionnaire Overall Life Impact Score at Weeks 12 and 26
Timepoint [4] 0 0
Baseline and Weeks 12 and 26
Secondary outcome [5] 0 0
Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26
Timepoint [5] 0 0
Baseline and Weeks 12 and 26
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
Weeks 1, 12 and 26
Secondary outcome [7] 0 0
Number of Participants Withdrawing Due to Lack of Efficacy During the First 26 Weeks of the Study
Timepoint [7] 0 0
Baseline to Week 26
Secondary outcome [8] 0 0
Number of Participants Rated as Normal or Borderline Ill on the CGI Severity of Illness (CGI-S) Scale at Week 26
Timepoint [8] 0 0
Week 26
Secondary outcome [9] 0 0
Median Time to First CGI-I Response of Much/Very Much Improved During the Double-blind Phase
Timepoint [9] 0 0
Baseline to Week 26
Secondary outcome [10] 0 0
Number of Participants With a Score of Much/Very Much Improved on the CGI-I Scale at Week 67
Timepoint [10] 0 0
Week 67
Secondary outcome [11] 0 0
Mean Change From Baseline in the IRLS Rating Scale Total Score at Week 67
Timepoint [11] 0 0
Baseline and Week 67

Eligibility
Key inclusion criteria
* 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:

1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or,
2. 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.
Minimum age
18 Years
Maximum age
79 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* 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.

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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2008
Sample size
Target
Accrual to date
Final
404
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Camperdown
Recruitment hospital [2] 0 0
GSK Investigational Site - Kippa Ring
Recruitment hospital [3] 0 0
GSK Investigational Site - Woodville
Recruitment hospital [4] 0 0
GSK Investigational Site - Clayton
Recruitment hospital [5] 0 0
GSK Investigational Site - East Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4021 - Kippa Ring
Recruitment postcode(s) [3] 0 0
5011 - Woodville
Recruitment postcode(s) [4] 0 0
3168 - Clayton
Recruitment postcode(s) [5] 0 0
3002 - East Melbourne
Recruitment outside Australia
Country [1] 0 0
Czech Republic
State/province [1] 0 0
Olomouc
Country [2] 0 0
Czech Republic
State/province [2] 0 0
Ostrava
Country [3] 0 0
Czech Republic
State/province [3] 0 0
Pardubice
Country [4] 0 0
Czech Republic
State/province [4] 0 0
Praha 2
Country [5] 0 0
Denmark
State/province [5] 0 0
Aalborg
Country [6] 0 0
Denmark
State/province [6] 0 0
Odense C
Country [7] 0 0
Denmark
State/province [7] 0 0
Vejle
Country [8] 0 0
Germany
State/province [8] 0 0
Bayern
Country [9] 0 0
Germany
State/province [9] 0 0
Hessen
Country [10] 0 0
Germany
State/province [10] 0 0
Mecklenburg-Vorpommern
Country [11] 0 0
Germany
State/province [11] 0 0
Niedersachsen
Country [12] 0 0
Germany
State/province [12] 0 0
Berlin
Country [13] 0 0
Italy
State/province [13] 0 0
Emilia-Romagna
Country [14] 0 0
Italy
State/province [14] 0 0
Lazio
Country [15] 0 0
Italy
State/province [15] 0 0
Lombardia
Country [16] 0 0
Norway
State/province [16] 0 0
Hamar
Country [17] 0 0
Portugal
State/province [17] 0 0
Coimbra
Country [18] 0 0
Portugal
State/province [18] 0 0
Lisboa
Country [19] 0 0
Slovakia
State/province [19] 0 0
Bratislava
Country [20] 0 0
Slovakia
State/province [20] 0 0
Dubnica nad Vahom
Country [21] 0 0
Slovakia
State/province [21] 0 0
Levoca
Country [22] 0 0
Slovakia
State/province [22] 0 0
Zilina
Country [23] 0 0
Spain
State/province [23] 0 0
Barcelona
Country [24] 0 0
Spain
State/province [24] 0 0
Madrid
Country [25] 0 0
Spain
State/province [25] 0 0
San Sebastián
Country [26] 0 0
Sweden
State/province [26] 0 0
Avesta
Country [27] 0 0
Sweden
State/province [27] 0 0
Göteborg
Country [28] 0 0
Sweden
State/province [28] 0 0
Örebro
Country [29] 0 0
Switzerland
State/province [29] 0 0
Bern
Country [30] 0 0
Switzerland
State/province [30] 0 0
Zürich

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00329602
Trial related presentations / 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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00329602